Method for using GLP-1 analogs and compositions thereof for the treatment of metabolic disorders

Abstract

This disclosure relates to methods for using GLP-1 analogs and compositions thereof for the treatment of metabolic disorders such as obesity, diabetes mellitus, metabolic dysfunction-related fatty liver disease (MASLD), metabolic dysfunction-related steatohepatitis (MASH), and hypertriglyceridemia. More specifically, this disclosure relates to a method for treating obesity in a subject, comprising administering a therapeutically effective dose of GL0034 to the subject. This disclosure also relates to a method for treating a metabolic disorder in a subject requiring it, comprising administering a therapeutically effective dose of GL0034 to the subject. This disclosure further relates to compositions comprising GL0034 for the treatment of obesity, diabetes mellitus, or other metabolic disorders in a subject.

Description

[Technical Field]

[0001] Cross-references to related applications This application claims the interests of Indian Patent Application No. 202321042015, filed on 20 June 2023, and Indian Patent Application No. 202421015451, filed on 1 March 2024, the disclosures of each thereof being incorporated herein by reference in their entirety.

[0002] Sequence List This application includes an electronically submitted sequence listing, which is incorporated herein by reference in its entirety. The sequence listing submitted with this specification is contained in an XML file created on June 6, 2024, named "23-0927-WO_Sequence-Listing.xml", and has a size of 4,096 bytes.

[0003] This disclosure relates to methods for using GLP-1 analogs and compositions thereof for the treatment of metabolic disorders such as obesity, diabetes mellitus, metabolic dysfunction-related fatty liver disease (MASLD) (sometimes referred to herein as non-alcoholic fatty liver disease (NAFLD)), metabolic dysfunction-related steatohepatitis (MASH) (sometimes referred to herein as non-alcoholic steatohepatitis (NASH)), and hypertriglyceridemia. More specifically, this disclosure relates to a method for treating obesity in a subject, comprising administering a therapeutically effective dose of GL0034 to the subject. This disclosure also relates to a method for treating a metabolic disorder in a subject requiring it, comprising administering a therapeutically effective dose of GL0034 to the subject. This disclosure further relates to compositions comprising GL0034 for the treatment of obesity, diabetes mellitus, or other metabolic disorders in a subject. [Background technology]

[0004] As of 2016, obesity was estimated to affect 13% of adults, nearly tripling since 1975. The World Health Organization's 2021 report, "Obesity and Overweight," is available on the World Health Organization website (accessed June 18, 2023). Approximately 2% of obese US adults were estimated to be receiving drug therapy for obesity in 2015. (Xia et al., Obesity (Silver Spring) 23(8):1721-28 (2015), Samaranayake et al., Ann. Epidemiol. 22(5):349-53 (2012)). Obesity significantly increases overall mortality in affected individuals, primarily due to its association with an increased risk of cardiovascular disease and diabetes. Global BMI Mortality Collaboration et al., Lancet 388(10046):776-86(2016), GBD 2015 Obesity Collaborators et al., N.Engl.J.Med.377(1):13-27(2017), Powell-Wiley et al., Circulation 143(21):e984-e1010(2021), Khan et al., JAMA Cardiol.3(4):280-87(2018), Nguyen et al., Obes.Surg.21(3):351-55(2011).

[0005] Diabetes is a chronic metabolic disease affecting approximately 422 million people worldwide and contributing to 1.5 million deaths annually. The World Health Organization's "Diabetes" is available on the World Health Organization's website (accessed June 18, 2023). Diabetes is characterized by elevated blood glucose levels that, over time, lead to serious damage to the heart, blood vessels, eyes, kidneys, and nerves. The most common type of diabetes is type 2 diabetes, which occurs when the body becomes resistant to insulin or fails to produce enough insulin.

[0006] Non-alcoholic fatty liver disease (NAFLD), now called metabolic dysfunction-associated fatty liver disease (MASLD), and non-alcoholic steatohepatitis (NASH), now called metabolic dysfunction-associated steatohepatitis (MASH), are highly associated with obesity and type 2 diabetes. Boland et al., Nat. Metab. 2(5):413-31 (2020), Rinella et al., Heptaology, 78(6):1966-86 (2023). NAFLD is very common in patients with type 2 diabetes, with approximately two-thirds of such patients being diagnosed with the condition. Cusi et al., Curr. Opin. Endocrinol. Diabetes Obes. 16(2):141-49 (2009). Furthermore, type 2 diabetes is an aggravating factor for NAFLD, as it increases the risk of developing NASH, hepatic fibrosis, cirrhosis, and hepatocellular carcinoma. El-Serag et al., Hepatology 60(5):1767-75(2014). Currently, the only validated treatment for NAFLD is weight loss.

[0007] Glucagon-like peptide-1 (GLP-1) is a hormone primarily produced in enteroendocrine L cells of the intestine and secreted into the bloodstream when foods containing fats, protein hydrolysates, or glucose enter the duodenum. GLP-1 originates from cell-specific post-translational processing of the preproglucagon gene. Initially, the peptide GLP-1(1-37) was identified from this processing, but it was later found to recognize pancreatic receptors and determined to be the active species in vivo: two N-terminal cleavage products, GLP-1(7-37) and GLP-1(7-36) amides. GLP-1 is known to stimulate insulin secretion, thereby causing cellular glucose uptake and a decrease in serum blood glucose levels.

[0008] Glucagon-like peptide-1 (GLP-1) receptor agonists have been shown to reduce glycated hemoglobin (HbA1c) and weight loss in type 2 diabetes. Andersen et al., Nat. Rev. Endocrinol. 14(7):390-403 (2018). Certain GLP-1 receptor agonists have been shown to improve glycemic control in adults with type 2 diabetes. Zhao et al., Front. Endocrinol. (Lausanne) 12:721135 (2021), Nauck et al., Mol. Metab. 46:101102 (2021). The glucose reduction by GLP-1 receptor agonists is due to a combination of actions, including direct action on pancreatic beta-cell GLP-1 receptors that enhance glucose-stimulated insulin secretion, inhibition of glucagon release, insulin sensitization due to weight loss, and a decrease in neuromediated glucose release from the liver. Muller et al., Mol. Metab. 30:72-130 (2019). Therefore, GLP-1 receptor agonists have been shown to be an appropriate therapy for individuals with type 2 diabetes. Buse et al., Diabetes Care 43(2):487-93 (2020).

[0009] In many cases, to reduce the associated risks caused by weight and metabolic status, overweight patients (≥27 kg / m²) with at least one weight-related metabolic comorbidity are treated. 2GLP-1 agonists such as semaglutide and tilzepatide are prescribed. The treatment is administered subcutaneously once a week in the abdomen, thigh, or upper arm. The initial dose of semaglutide (WEGOVY®) is 0.25 mg once a week for 4 weeks, followed by dose adjustments every 4 weeks to reach a maintenance dose of 1.7 mg to 2.4 mg (see WEGOVY® label). The initial dose of tilzepatide (ZEPBOUND®) is 2.5 mg once a week for 4 weeks, followed by dose increases in increments of 2.5 mg at least after 4 weeks, with a maintenance dose of 5 mg, 10 mg, or 15 mg (see ZEPBOUND® label).

[0010] Treatment with GLP-1 receptor agonists also offers further beneficial metabolic effects, such as improved lipid profiles and the disappearance of fatty liver. Jones et al., Diabetes Obes. Metab. 24(11):2090-101 (2022). Animal model studies suggest that certain GLP-1 receptor agonists may have beneficial effects on hepatic fat content and non-alcoholic steatohepatitis (NASH), while recent human studies evaluating GLP-1 receptor agonists in type 2 diabetes and obese populations suggest that treatment with certain GLP-1 receptor agonists may be a new option for the management of non-alcoholic fatty liver disease (NAFLD) and NASH. Newsome et al., Aliment. Pharmacol. Ther. 50(2):193-203 (2019), Newsome et al., N.Engl. J.Med., 384(12):1113-24 (2021). Certain GLP-1 receptor agonists have also been shown to reduce body weight in obese individuals. Ma et al., Int.J.Biol.Sci.17(8):2050-68(2021), Ard et al., Adv.Ther.38(6):2821-39(2021).

[0011] GL0034 is a novel incretin analog based on the sequence of natural GLP-1 and possesses potent, G protein-biased, long-acting agonist activity at the GLP-1 receptor, effectively reducing blood glucose and triglyceride levels as well as body weight in mice. (Jones et al., Diabetes Obes. Metab. 24(11):2090-101(2022)). While this agonist shares some structural homology with other GLP-1 receptor agonists, it has a distinct linker sequence between its polypeptide chain and albumin-binding acyl group, which may affect its pharmacological properties. (Ibid.) The in vitro and in vivo performance of GL0034 compared to other commercially available compounds using various models has been described. (Ibid.) International Publication No. 2019 / 193576A1 discloses a group of novel GLP-1 receptor agonists (or analogues) having an amino acid sequence (SEQ ID NO: 1 shown below in Formula I) with a leucine or isoleucine residue at the C-terminus, and which are acylated in an extended portion to further improve their potency and duration of action. The entire publication is incorporated herein by reference. GL0034 (see compound number 16 in Table 2 of International Publication No. 2019 / 193576A1) may be represented by a compound of the following formula: Formula I: [ka] [Overview of the Initiative]

[0012] This disclosure relates to methods and compositions for the treatment of obesity. This disclosure also relates to methods and compositions for the treatment of metabolic disorders such as metabolic dysfunction-related fatty liver disease (MASLD), metabolic dysfunction-related steatohepatitis (MASH), diabetes mellitus, and hypertriglyceridemia. More specifically, this disclosure relates to a method for treating obesity in a subject, comprising administering a therapeutically effective dose of GL0034 to the subject. This disclosure also relates to a method for treating a metabolic disorder in a subject requiring it, comprising administering a therapeutically effective dose of GL0034 to the subject. This disclosure further relates to a method for treating hypertension in a subject, comprising administering a therapeutically effective dose of GL0034 to the subject. This disclosure further relates to compositions comprising GL0034 for the treatment of obesity or metabolic disorders or hypertension in a subject.

[0013] This specification provides a method for treating obesity in a subject, comprising administering a therapeutically effective dose of GL0034 to the subject. This specification also provides a method for treating metabolic disorders in a subject, comprising administering a therapeutically effective dose of GL0034 to the subject. This specification further provides a method for treating hypertension in a subject, comprising administering a therapeutically effective dose of GL0034 to the subject.

[0014] This specification further provides pharmaceutical compositions comprising GL0034 for the treatment of obesity in subjects. This specification further provides pharmaceutical compositions comprising GL0034 for the treatment of metabolic disorders in subjects. This specification further provides pharmaceutical compositions comprising GL0034 for the treatment of hypertension in subjects.

[0015] This specification further provides the use of GL0034 for the manufacture of drugs for treating obesity in subjects. This specification further provides the use of GL0034 for the manufacture of drugs for treating metabolic disorders in subjects. This specification further provides the use of GL0034 for the manufacture of drugs for treating hypertension in subjects.

[0016] These and other features and advantages of this disclosure will be better understood from the following detailed description, along with the attached claims. Note that the claims are defined by their enumeration rather than by specific descriptions of the features and advantages described herein. [Brief explanation of the drawing]

[0017] [Figure 1] Figure 1 shows the study design for selection, randomization, and treatment of lean men in repeated dose escalation of GL0034. AE stands for Adverse Event, ALT for Alanine Transaminases, BMI for Body Mass Index, HbA1C for Hemoglobin A1C, HOMA-IR for Assessment of Insulin Resistance Homeostasis Model, and PD for Pharmacodynamics. [Figure 2A] Figure 2A shows a bar graph representing the mean change in weight in kilograms on day 29. Weight changes over time were analyzed using a paired Student's t-test, performed using GraphPad Prism 9 (version 9.5.1), LLC, Boston, Massachusetts. Missing data were not imputed. Data labels indicate the mean absolute change / percentage change from baseline. A comparison of Cohorts 1 and 2 on day 29 is shown. *** indicates a comparison with the value on day 1, where P<0.001. [Figure 2B] Figure 2B shows a bar graph representing the mean change in weight in kilograms on day 52. ​​Weight changes over time were analyzed using a paired Student's t-test performed with GraphPad Prism 9 (version 9.5.1) LLC, Boston, Massachusetts. Missing data were not imputed. Data labels indicate the mean absolute change from baseline / percentage change. For Cohort 3, a comparison at day 52 is shown. *** indicates a comparison with the value on day 1, where P<0.001. [Figure 3A]Figure 3A shows a bar graph illustrating the mean change in alanine transaminase (ALT) levels (U / L) on day 23. Changes in ALT over time were analyzed using paired Student's t-tests performed with GraphPad Prism 9 (version 9.5.1) LLC, Boston, Massachusetts. Missing data were not imputed. Data labels indicate the mean absolute change / percentage change from baseline. Comparisons for cohorts 1 and 2 on day 23 are shown. * indicates a P<0.05 and represents a comparison with the value on day 1. [Figure 3B] Figure 3B shows a bar graph illustrating the mean change in alanine transaminase (ALT) levels (U / L) on day 51. Changes in ALT over time were analyzed using paired Student's t-tests performed with GraphPad Prism 9 (version 9.5.1) LLC, Boston, Massachusetts. Missing data were not imputed. Data labels indicate the mean absolute change / percentage change from baseline. For Cohort 3, a comparison at day 51 is shown. * indicates a P<0.05 and represents a comparison with the value on day 1. [Figure 4A] Figure 4A shows bar graphs illustrating the mean change in fasting insulin for all three cohorts on day 23. Changes in fasting insulin over time were analyzed using paired Student's t-tests performed with GraphPad Prism 9 (version 9.5.1) LLC, Boston, Massachusetts. Missing data were not imputed. Data labels indicate the mean absolute change from baseline / percentage change. A comparison of cohorts 1 and 2 on day 23 is shown. [Figure 4B] Figure 4B shows bar graphs illustrating the mean change in fasting insulin at day 51 across all three cohorts. Changes in fasting insulin over time were analyzed using paired Student's t-tests performed with GraphPad Prism 9 (version 9.5.1) LLC, Boston, Massachusetts. Missing data were not imputed. Data labels indicate the mean absolute change from baseline / percentage change. A comparison at day 51 is shown for Cohort 3. [Figure 5A] Figure 5A shows a bar graph at day 23 illustrating the changes in the Homeostasis Model Assessment (HOMA-IR) level for insulin resistance. Changes in HOMA-IR over time were analyzed using paired Student's t-tests performed with GraphPad Prism 9 (version 9.5.1) LLC, Boston, Massachusetts. Missing data were not imputed. HOMA-IR < 1.0 indicates optimal insulin sensitivity, HOMA-IR > 1.9 indicates early insulin resistance, and HOMA-IR > 2.9 indicates clinically significant insulin resistance. Data labels show the mean HOMA-IR. A comparison at day 23 is shown for cohorts 1 and 2. [Figure 5B] Figure 5B shows a bar graph at day 51 illustrating the changes in the Homeostasis Model Assessment (HOMA-IR) level for insulin resistance. Changes in HOMA-IR over time were analyzed using paired Student's t-tests performed with GraphPad Prism 9 (version 9.5.1) LLC, Boston, Massachusetts. Missing data were not imputed. HOMA-IR < 1.0 indicates optimal insulin sensitivity, HOMA-IR > 1.9 indicates early insulin resistance, and HOMA-IR > 2.9 indicates clinically significant insulin resistance. Data labels show the mean HOMA-IR. A comparison at day 51 is shown for Cohort 3. [Figure 6] Figure 6 shows the study design for the selection, randomization, and treatment of obese individuals in a single dose escalation of GL0034. BMI is the body mass index, HbA1C is hemoglobin A1C, PD is pharmacodynamics, and PK is pharmacokinetics. [Figure 7] Figure 7 is a plasma concentration-time curve showing the average plasma GL0034 concentration over time. [Figure 8]Figure 8 shows a graph of the mean change in body weight (kg) on ​​days 8, 15, and 22 (EOS - end of the study). Changes in body weight over time were analyzed using paired one-way ANOVA, followed by Dunnett's posthoc test, with GraphPad Prism 9 (version 9.5.1), LLC, Boston, Massachusetts. Missing data were not imputed. Data labels indicate the mean absolute change from baseline in kg. * indicates P<0.05, ** indicates P<0.01, and *** indicates P<0.001, respectively, and are comparisons to body weight on day 1. [Figure 9A] Figure 9A shows a bar graph illustrating the mean change in triglyceride levels (ng / ml) for all participants. # indicates P<0.05, ## indicates P<0.01, and these represent comparisons to the values ​​on day 1. Paired Student's t-tests were performed using GraphPad Prism 9 (version 9.5.1). Missing values ​​were not imputed. Data labels indicate the mean absolute change / percentage change from baseline. [Figure 9B] Figure 9B shows a bar graph illustrating the mean change in leptin levels (ng / ml) for all participants. # indicates P<0.05, ## indicates P<0.01, and these represent comparisons to the values ​​on day 1. Paired Student's t-tests were performed using GraphPad Prism 9 (version 9.5.1). Missing values ​​were not imputed. Data labels indicate the mean absolute change / percentage change from baseline. [Modes for carrying out the invention]

[0018] This disclosure relates to methods and compositions for the treatment of obesity. This disclosure also relates to methods and compositions for the treatment of metabolic disorders such as metabolic dysfunction-related fatty liver disease (MASLD), metabolic dysfunction-related steatohepatitis (MASH), diabetes mellitus, and hypertriglyceridemia. More specifically, this disclosure relates to a method for treating obesity in a subject, comprising administering a therapeutically effective dose of GL0034 to the subject. This disclosure also relates to a method for treating a metabolic disorder in a subject requiring it, comprising administering a therapeutically effective dose of GL0034 to the subject. This disclosure also relates to a method for treating hypertension in a subject, comprising administering a therapeutically effective dose of GL0034 to the subject. This disclosure further relates to compositions comprising GL0034 for the treatment of obesity or metabolic disorders or hypertension in a subject.

[0019] When used in accordance with this disclosure, unless otherwise indicated, all technical and scientific terms used herein are understood to have the meanings generally understood by those skilled in the art of the field to which this disclosure belongs. The following references provide general definitions of many of the terms used in this disclosure: Singleton et al., Dictionary of Microbiology and Molecular Biology (2nd ed. 1994); The Cambridge Dictionary of Science and Technology (Walker ed., 1988); The Glossary of Genetics, 5th Ed., R. Rieger et al. (eds.), Springer Verlag (1991); and Hale & Marham, The Harper Collins Dictionary of Biology (1991). When used herein, the following terms have the meanings set forth below unless otherwise specified.

[0020] Unless otherwise specified by the context, singular terms shall include plural forms, and plural terms shall include singular forms. For example, as used herein, the words “a,” “an,” and “the” shall be understood to be singular or plural unless otherwise explicitly indicated by the context. As used herein, the words “a” and “an” shall be understood to refer to “one or more” of the enumerated components unless otherwise indicated or determined by the context. The use of alternative expressions (e.g., “or”) shall be understood to mean one, both, or any combination thereof of the alternative expression unless otherwise indicated. Thus, as used herein, the word “or” shall be understood to be inclusive unless specifically stated or obvious from the context.

[0021] As used herein, the terms “comprise” and “comprising” may have the meanings described in U.S. Patent Law, and may mean “include,” “including,” “containing,” “having,” etc. That is, unless otherwise expressly designated, as used herein, the terms “comprise” and “comprising” indicate that in addition to the listed components or members introduced by “comprising,” further components or members may be optionally included. As used herein, the terms “consisting essentially of” or “consists essentially” similarly have the meanings described in U.S. Patent Law, and allow for more than the listed entities, unless the basic or novel features of the listed entities are altered by more than the listed entities.

[0022] Any method or composition provided herein can be combined with one or more of the other methods or compositions provided herein.

[0023] In this disclosure, unless otherwise indicated, any range of concentration, percentage, ratio, or integer should be understood to include any integer values ​​within the enumerated range, and, where appropriate, fractions thereof (such as one-tenth and one-hundredth of an integer). The ranges provided herein should be understood to omit all values ​​within that range. For example, the range 1 to 50 is understood to include any number, combination of numbers, or sub-range from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50.

[0024] Unless otherwise stated or evident from the context, the terms “about” and “approximately” as used herein are understood to mean an average value within the normal tolerances in the art, e.g., within two standard deviations of the mean, or within the acceptable margin of error for a particular value as determined by a person skilled in the art, which will depend in part on how the value is measured or determined, i.e., the limits of the measurement system. “About” may be understood to mean within 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, 0.1%, 0.05%, or 0.01% of the stated value. Unless otherwise evident from the context, all numerical values ​​provided herein are modified by the term “about.”

[0025] It should be noted that terms such as “preferably,” “commonly,” and “typically” are not used herein to limit the scope of the subject matter described in the claims, or to imply that certain features are significant, essential, or even important to the structure or function of the subject matter described in the claims. Rather, these terms are intended merely to highlight alternative or additional features that may or may not be available in the particular embodiments of this disclosure.

[0026] In order to describe and govern this disclosure, it should be noted that the term “substantially” is used herein to describe the degree of inherent uncertainty that may accompany any quantitative comparison, value, measurement, or other expression. The term “substantially” is also used to describe the extent to which a quantitative expression may deviate from the stated standard without altering the fundamental function of the subject matter at issue.

[0027] Methods and compositions In one embodiment, the disclosure provides a method for treating obesity in a subject, comprising administering a therapeutically effective dose of GL0034 to the subject. In another embodiment, the disclosure provides a method for treating metabolic disorders in a subject, comprising administering a therapeutically effective dose of GL0034 to the subject.

[0028] In one embodiment, the disclosure provides a pharmaceutical composition comprising GL0034 for the treatment of obesity in a subject. In another embodiment, the disclosure provides a pharmaceutical composition comprising GL0034 for the treatment of metabolic disorders in a subject.

[0029] In one embodiment, the disclosure provides the use of GL0034 for the manufacture of a drug for treating obesity in a subject. In another embodiment, the disclosure provides the use of GL0034 for the manufacture of a drug for treating metabolic disorders in a subject.

[0030] As used herein, the terms “subject,” “patient,” and “participant” are interchangeable. In some embodiments, the subject or patient is a mammal. In some embodiments of the methods, compositions, and agents of this disclosure, the subject is diabetic. In other embodiments of the methods, compositions, and agents of this disclosure, the subject is not diabetic. In some embodiments of the methods, compositions, and agents of this disclosure, the subject is at least 18 kg / m² 2 They have a Body Mass Index (BMI) of [value missing].

[0031] As used herein, “diabetes,” “diabetes mellitus,” or “diabetic” refers to a metabolic disorder / disorder associated with elevated blood glucose levels. The term also includes all types of diabetes, with the three main, non-limiting types being type 1 diabetes (T1DM), type 2 diabetes (T2DM), and gestational diabetes.

[0032] As used herein, “Disorder” is any condition that would benefit from treatment under GL0034. “Disorder” and “condition” are used interchangeably herein and include chronic and acute disorders or diseases, including pathological conditions that make a patient susceptible to the disorder in question.

[0033] As used herein, the terms “treatment” or “to treat” refer to both therapeutic actions and preventive or protective measures. Subjects requiring treatment include those with obesity, metabolic disorder-related fatty liver disease (MASLD), metabolic disorder-related steatohepatitis (MASH), or diabetes.

[0034] In some embodiments of the methods, compositions, and agents of this disclosure, the metabolic disorder is metabolic dysfunction-associated fatty liver disease (MASLD). In certain embodiments of the methods, compositions, and agents of this disclosure, MASLD is metabolic dysfunction-associated steatohepatitis (MASH). In some embodiments of the methods, compositions, and agents of this disclosure, the metabolic disorder is diabetes mellitus. In certain embodiments of the methods, compositions, and agents of this disclosure, the metabolic disorder is type 2 diabetes mellitus. In other embodiments, the metabolic disorder is hypertriglyceridemia.

[0035] As used herein, the terms “pharmaceutical composition” or “therapeutic composition” refer to a compound or composition that, when appropriately administered to a patient, can induce a desired therapeutic effect. One embodiment of the present disclosure provides a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of GL0034.

[0036] As used herein, the terms “pharmaceutically acceptable carrier” or “physiologically acceptable carrier” refer to one or more formulations suitable for achieving or enhancing the delivery of GL0034.

[0037] The present invention provides pharmaceutical compositions comprising GL0034 alone or in combination with prophylactic agents, therapeutic agents, and / or pharmaceutically acceptable carriers. The pharmaceutical compositions comprising GL0034 provided herein are intended for use in the prevention, treatment, management, or improvement of a disorder or one or more symptoms thereof, but are not limited thereto. Formulation of pharmaceutical compositions, either alone or in combination with prophylactic agents, therapeutic agents, and / or pharmaceutically acceptable carriers, is known to those skilled in the art.

[0038] As used herein, the terms “administer” or “to administer” mean providing, contacting, and / or delivering GL0034 by any suitable route to achieve a desired effect. Administration may include, but is not limited to, oral administration, sublingual administration, parenteral administration (e.g., intravenous injection, subcutaneous injection, intradermal injection, intramuscular injection, intra-articular injection, intra-arterial injection, intra-bursal injection, intracisional injection, intrathecal injection, intrafocal injection, or intracranial injection), transdermal administration, topical administration, oral administration, rectal administration, vaginal administration, nasal administration, eye drops, inhalation, and implantation. In some embodiments of the methods, compositions, and pharmaceuticals of this disclosure, GL0034 (or compositions or pharmaceuticals comprising GL0034) is administered subcutaneously to a subject. In certain embodiments of the methods, compositions, and pharmaceuticals of this disclosure, administration is by subcutaneous injection. In certain embodiments of the methods, compositions, and pharmaceuticals of this disclosure, administration is performed subcutaneously via an auto-injector or pre-filled syringe.

[0039] In some embodiments of the methods, compositions, and pharmaceuticals of this disclosure, the dose of GL0034 (or a composition or pharmaceutical containing GL0034) administered to a subject is 200 μg to 8000 μg of GL0034, 300 μg to 6000 μg of GL0034, 400 μg to 4000 μg of GL0034, or 1000 μg to 3000 μg of GL0034. In certain embodiments of the methods, compositions, and pharmaceuticals of this disclosure, the dose of GL0034 (or a composition or pharmaceutical containing GL0034) administered to a subject is 450 μg, 680 μg, 900 μg, 1520 μg, 2000 μg, or 2520 μg of GL0034. In certain embodiments of the methods, compositions, and pharmaceuticals of this disclosure, a single dose of GL0034 (or a composition or pharmaceutical containing GL0034) is administered to the target, and the dose of GL0034 (or a composition or pharmaceutical containing GL0034) is 1520 μg, 2000 μg, or 2520 μg of GL0034.

[0040] In some embodiments of the methods, compositions, and pharmaceuticals of this disclosure, GL0034 (or compositions or pharmaceuticals comprising GL0034) is administered daily, every other day, every three days, every four days, every five days, every six days, once a week, or once every two weeks. In one embodiment of the methods, compositions, and pharmaceuticals of this disclosure, GL0034 (or compositions or pharmaceuticals comprising GL0034) is administered once a week. As used herein, the term "Day 1" refers to the first day on which GL0034 (or compositions or pharmaceuticals comprising GL0034) is administered to the subject.

[0041] In some embodiments of the methods, compositions, and agents of this disclosure, GL0034 (or a composition or agent containing GL0034) is administered over a treatment period of two weeks, four weeks, six weeks, or eight weeks. In one embodiment of the methods, compositions, and agents of this disclosure, GL0034 (or a composition or agent containing GL0034) is administered to a subject once a week for a maximum of four weeks. In another embodiment of the methods, compositions, and agents of this disclosure, GL0034 (or a composition or agent containing GL0034) is administered to a subject once a week for a maximum of eight weeks.

[0042] In one embodiment of the methods, compositions, and agents disclosed herein, the average highest concentration (C) of GL0034 is used. max The area under the concentration-time curve (AUC) of GL0034 is 226.9±57.3 ng / mL to 367.0±152.0 ng / mL. In certain embodiments of the methods, compositions, and agents of this disclosure, the administration of GL0034 (or a composition or agent containing GL0034) over a period of 22 days is 47,151.5±16,838.6 ng*h / mL to 62,265.9±20,816.5 ng*h / mL. 0-t ) provides. In certain embodiments of the methods, compositions, and agents of this disclosure, administration of GL0034 (or a composition or agent comprising GL0034) provides a plasma drug half-life (t) of GL0034, where GL0034 has a half-life of 98.5 ± 13.0 hours to 113.5 ± 22.9 hours. 1 / 2) is provided. In certain embodiments of the methods, compositions, and agents of the present disclosure, administration of GL0034 (or a composition or agent comprising GL0034) results in a time from administration to maximum plasma concentration (T max ) that is provided.

[0043] In one embodiment of the methods, compositions, and agents of the present disclosure, GL0034 (or a composition or agent comprising GL0034) is administered at a dose of GL0034 that is 450 μg once a week for 4 weeks, and the average maximum concentration (C max ) is 100.5 ± 22.0 ng / mL to 141.7 ± 34.6 ng / mL. In certain embodiments of the methods, compositions, and agents of the present disclosure, administration of GL0034 (or a composition or agent comprising GL0034) provides an area under the plasma concentration-time curve (AUC 0-t ) of GL0034 that is 12814.3 ± 2652.1 ng*h / mL to 18536.8 ± 4608.0 ng*h / mL over a period of 22 days. In certain embodiments of the methods, compositions, and agents of the present disclosure, administration of GL0034 (or a composition or agent comprising GL0034) provides a plasma drug half-life (t 1 / 2 ) of GL0034 that is 102.3 ± 15.4 hours by day 22. In certain embodiments of the methods, compositions, and agents of the present disclosure, administration of GL0034 (or a composition or agent comprising GL0034) results in a time from administration to maximum plasma concentration (T max ) that is 36.0 ± 12.0 hours to 47.0 ± 16.0 hours.

[0044] In one embodiment of the methods, compositions, and agents of the present disclosure, GL0034 (or a composition or agent comprising GL0034) is administered at a dose of GL0034 that is 680 μg once a week for 4 weeks, and the average maximum concentration (C maxThe area under the concentration-time curve (AUC) of GL0034 is 169.0±49.5 ng / mL to 267.0±60.9 ng / mL over a period of 22 days. In certain embodiments of the methods, compositions, and agents of this disclosure, the administration of GL0034 (or a composition or agent containing GL0034) is 24575.9±3391.3 ng*h / mL to 34536.6±6445.0 ng*h / mL over a period of 22 days. 0-t ) provides. In certain embodiments of the methods, compositions, and agents of this disclosure, administration of GL0034 (or a composition or agent containing GL0034) by day 22 has a plasma drug half-life (t) of GL0034 of 122.9 ± 16.5 hours. 1 / 2 ) provides. In certain embodiments of the methods, compositions, and agents of this disclosure, administration of GL0034 (or a composition or agent containing GL0034) provides the time to reach the peak plasma concentration of GL0034 (T) which is 39.0 ± 21.0 hours to 54.0 ± 27.0 hours. max ) provides.

[0045] In one embodiment of the methods, compositions, and pharmaceuticals of the present disclosure, (i) a dose of GL0034 of 450 μg is administered to the subject once a week for two weeks, followed by (ii) a dose of GL0034 of 900 μg is administered to the subject once a week for two weeks, followed by (iii) a dose of GL0034 of 1520 μg is administered to the subject once a week for four weeks. In certain embodiments of the methods, compositions, and pharmaceuticals of the present disclosure, the average peak concentration (C) of GL0034 is max The area under the concentration-time curve (AUC) of GL0034 is 111.7±23.7 ng / mL to 707.6±251.7 ng / mL over a period of 50 days. In certain embodiments of the methods, compositions, and agents of this disclosure, the administration of GL0034 (or a composition or agent containing GL0034) is 12942.2±1517.5 ng*h / mL to 76320.4±23334.6 ng*h / mL over a period of 50 days. 0-t ) provides. In certain embodiments of the methods, compositions, and agents of this disclosure, administration of GL0034 (or a composition or agent containing GL0034) by day 50 has a plasma drug half-life (t) of GL0034 of 106.8 ± 33.8 hours.1 / 2 ) provides. In certain embodiments of the methods, compositions, and agents of this disclosure, administration of GL0034 (or a composition or agent comprising GL0034) provides the time to reach peak plasma concentration of GL0034 (T) which is 22.0 ± 16.0 hours to 41.0 ± 8.0 hours. max ) provides.

[0046] In some embodiments of the methods, compositions, and agents of this disclosure, administration of GL0034 (or a composition or agent comprising GL0034) results in one or more clinically significant changes from baseline in a subject, the clinically significant changes from baseline being a decrease in alanine transaminase (ALT) levels, a decrease in aspartate aminotransferase (AST) levels, a decrease in gamma-glutamyltransferase (GGT) levels, a decrease in fasting insulin levels, a decrease in fasting blood glucose levels, a decrease in glycated hemoglobin (%HbA1c), a decrease in the homeostasis model assessment of insulin resistance (HOMA-IR), a decrease in body weight, a decrease in leptin levels, a decrease in triglyceride (TG) levels, a decrease in total cholesterol (TC) levels, a decrease in low-density lipoprotein (LDL) levels, an increase in high-density lipoprotein (HDL) levels, and / or a decrease in the TG / HDL ratio.

[0047] In one embodiment of the methods, compositions, and agents of this disclosure, the decrease in ALT levels from baseline is sustained for up to 23 days, up to 52 days, or up to 78 days. In certain embodiments of the methods, compositions, and agents of this disclosure, the change in ALT levels from baseline is at least -8.8 ± 13.1 U / L over a period of approximately 23 days after administration of GL0034 (or a composition or agent containing GL0034), or at least -3.1 ± 5.8 U / L over a period of approximately 23 days after administration of GL0034 (or a composition or agent containing GL0034), or at least -7.4 ± 10.3 U / L over a period of approximately 51 days after administration of GL0034 (or a composition or agent containing GL0034), or at least -1.0 ± 9.4 U / L over a period of approximately 78 days after administration of GL0034 (or a composition or agent containing GL0034).

[0048] In one embodiment of the methods, compositions, and agents of the present disclosure, the decrease in AST levels from baseline is sustained for up to 23 days, up to 51 days, or up to 78 days. In certain embodiments of the methods, compositions, and agents of the present disclosure, the change in AST levels from baseline is at least -4.0 ± 7.5 U / L over a period of approximately 51 days after administration of GL0034 (or a composition or agent containing GL0034), or at least -1.1 ± 6.7 U / L over a period of approximately 78 days after administration of GL0034 (or a composition or agent containing GL0034).

[0049] In one embodiment of the methods, compositions, and agents of the present disclosure, the decrease in GGT levels from baseline is sustained for up to 23 days, up to 51 days, or up to 78 days. In certain embodiments of the methods, compositions, and agents of the present disclosure, the change in GGT levels from baseline is at least -3.4 ± 3.5 U / L over a period of approximately 51 days after administration of GL0034 (or a composition or agent containing GL0034), or at least -1.0 ± 2.7 U / L over a period of approximately 78 days after administration of GL0034 (or a composition or agent containing GL0034).

[0050] In one embodiment of the methods, compositions, and agents of the present disclosure, the decrease in fasting insulin levels from baseline is sustained for up to 23 days or up to 51 days. In certain embodiments of the methods, compositions, and agents of the present disclosure, the change in fasting insulin levels from baseline is at least -4.6 ± 23.0 pmol / L over a period of approximately 23 days after administration of GL0034 (or a composition or agent containing GL0034) or at least -11.3 ± 16.5 pmol / L over a period of approximately 51 days after administration of GL0034 (or a composition or agent containing GL0034).

[0051] In one embodiment of the methods, compositions, and agents of the present disclosure, the reduction in fasting glucose lasts for up to 23 days or up to 51 days. In certain embodiments of the methods, compositions, and agents of the present disclosure, the reduction in fasting glucose is at least -2.8 ± 3.7 mg / dL over a period of approximately 23 days after administration of GL0034 (or a composition or agent containing GL0034), or at least -4.6 ± 2.7 mg / dL over a period of approximately 23 days after administration of GL0034 (or a composition or agent containing GL0034), or at least -7.7 ± 9.9 mg / dL over a period of approximately 51 days after administration of GL0034 (or a composition or agent containing GL0034).

[0052] In one embodiment of the methods, compositions, and agents of the present disclosure, the reduction in HbA1c is at least -0.25 ± 0.2 over a period of approximately 78 days following administration of GL0034 (or a composition or agent containing GL0034).

[0053] In one embodiment of the methods, compositions, and agents of the present disclosure, the reduction in HOMA-IR is achieved on day 23 after administration of GL0034 (or a composition or agent containing GL0034), or on day 51 after administration of GL0034 (or a composition or agent containing GL0034).

[0054] In one embodiment of the methods, compositions, and agents of the present disclosure, the weight loss lasts for up to 8 days, up to 15 days, up to 22 days, up to 29 days, up to 50 days, up to 52 days, or up to 78 days. In a particular embodiment of the methods, compositions, and agents of the present disclosure, the weight loss is at least -1.8 ± 2.4 kg over a period of about 22 days after administration of GL0034 (or a composition or agent containing GL0034), or at least -2.4 ± 2.2 kg over a period of about 22 days after administration of GL0034 (or a composition or agent containing GL0034), or at least -3.1 ± 1.7 kg over a period of about 22 days after administration of GL0034 (or a composition or agent containing GL0034), or GL0034 (or GL0034 The weight is at least -3.4±1.8 kg over a period of approximately 29 days after administration of a composition or drug containing GL0034, or at least -4.1±1.0 kg over a period of approximately 29 days after administration of GL0034 (or a composition or drug containing GL0034), or at least -7.7±1.9 kg over a period of approximately 52 days after administration of GL0034 (or a composition or drug containing GL0034), or at least -6.4±2.1 kg over a period of approximately 78 days after administration of GL0034 (or a composition or drug containing GL0034).

[0055] In one embodiment of the methods, compositions, and agents of this disclosure, the decrease in leptin levels from baseline is dose-dependent. In certain embodiments of the methods, compositions, and agents of this disclosure, the change in leptin levels from baseline is at least -6.9 ± 5.1 ng / mL over a period of approximately 8 days after administration of GL0034 (or a composition or agent containing GL0034), or at least -10.9 ± 8.6 ng / mL over a period of approximately 8 days after administration of GL0034 (or a composition or agent containing GL0034), or at least -11.6 ± 12.8 ng / mL over a period of approximately 8 days after administration of GL0034 (or a composition or agent containing GL0034).

[0056] In one embodiment of the methods, compositions, and agents of the present disclosure, the reduction in TG from baseline is observed on day 8 after administration of GL0034 (or a composition or agent containing GL0034) and may persist for up to 51 or 78 days. In certain embodiments of the methods, compositions, and agents of this disclosure, the change in TG levels from baseline is at least -0.4 ± 0.4 mmol / L over a period of about 8 days after administration of GL0034 (or a composition or agent containing GL0034), or at least -0.5 ± 0.5 mmol / L over a period of about 22 days after administration of GL0034 (or a composition or agent containing GL0034), or at least -0.8 ± 0.5 mmol / L over a period of about 8 days after administration of GL0034 (or a composition or agent containing GL0034), or at least -21.0 ± 27.5 mg / dL over a period of about 51 days after administration of GL0034 (or a composition or agent containing GL0034), or at least -11.0 ± 55.3 mg / dL over a period of about 78 days after administration of GL0034 (or a composition or agent containing GL0034).

[0057] In one embodiment of the methods, compositions, and agents of the present disclosure, the change in TC level from baseline is at least -29.1 ± 23.3 mg / dL over a period of approximately 51 days after administration of GL0034 (or a composition or agent containing GL0034), or at least -5.8 ± 12.6 mg / dL over a period of approximately 78 days after administration of GL0034 (or a composition or agent containing GL0034).

[0058] In one embodiment of the methods, compositions, and agents of the present disclosure, the change in LDL level from baseline is at least -24.0 ± 24.3 mg / dL over a period of approximately 51 days after administration of GL0034 (or a composition or agent containing GL0034), or at least -19.5 ± 35.8 mg / dL over a period of approximately 78 days after administration of GL0034 (or a composition or agent containing GL0034).

[0059] In one embodiment of the methods, compositions, and agents of this disclosure, the increase in HDL level from baseline is at least 2.9 ± 3.1 mg / dL over a period of approximately 78 days following administration of GL0034 (or a composition or agent containing GL0034).

[0060] In one embodiment of the methods, compositions, and agents of this disclosure, administration of GL0034 (or a composition or agent containing GL0034) results in a time-dependent decrease in the frequency of adverse events (AEs) in a subject. In certain embodiments of the methods, compositions, and agents of this disclosure, the AEs are one or more of nausea, vomiting, and / or loss of appetite. In other embodiments of the methods, compositions, and agents of this disclosure, the decrease in the frequency of AEs is dose-dependent.

[0061] As used herein, the terms “group” and “cohort” have the same meaning.

[0062] Embodiments: Embodiment 1: A pharmaceutical composition comprising GL0034 for the treatment of obesity in a subject. Embodiment 2: The subject is the pharmaceutical composition described in Embodiment 1, which is not for diabetes. Embodiment 3: The target group is individuals with a Body Mass Index (BMI) of at least 28 kg / m². 2 is either ≥27kg / m 2 A pharmaceutical composition according to either Embodiment 1 or Embodiment 2, wherein the patient has at least one weight-related comorbidity. Embodiment 4: A pharmaceutical composition comprising GL0034 for the treatment of metabolic disorders in a subject. Embodiment 5: The pharmaceutical composition according to Embodiment 4, wherein the metabolic disorder is metabolic dysfunction-related fatty liver disease (MASLD). Embodiment 6: The pharmaceutical composition according to Embodiment 5, wherein MASLD is metabolic disorder-associated steatohepatitis (MASH). Embodiment 7: The pharmaceutical composition according to Embodiment 4, wherein the metabolic disorder is diabetes mellitus or hypertriglyceridemia. Embodiment 8: The pharmaceutical composition according to Embodiment 7, wherein the metabolic disorder is type 2 diabetes. Embodiment 9: The subject is a pharmaceutical composition according to any one of Embodiments 1 to 8, for a person with hypertension. Embodiment 10: The pharmaceutical composition is a pharmaceutical composition according to any one of Embodiments 1 to 9, which is administered subcutaneously to a subject. Embodiment 11: The pharmaceutical composition is the pharmaceutical composition according to Embodiment 10, which is administered to a subject by subcutaneous injection. Embodiment 12: The pharmaceutical composition according to Embodiment 11, wherein the pharmaceutical composition is administered to a subject using an auto-injector or a pre-filled syringe. Embodiment 13: The pharmaceutical composition is a pharmaceutical composition according to any one of Embodiments 1 to 12, wherein the dosage of the pharmaceutical composition is 200 μg to 8000 μg of GL0034. Embodiment 14: The pharmaceutical composition according to Embodiment 13, wherein the dosage of the pharmaceutical composition is 300 μg to 6000 μg of GL0034. Embodiment 15: The pharmaceutical composition according to Embodiment 14, wherein the dosage of the pharmaceutical composition is 400 μg to 4000 μg of GL0034. Embodiment 16: The pharmaceutical composition according to Embodiment 15, wherein the dosage of the pharmaceutical composition is 1000 μg to 3000 μg of GL0034. Embodiment 17: The dosage of the pharmaceutical composition is the pharmaceutical composition according to any one of Embodiments 1 to 16, administered to the subject once a week or once every two weeks. Embodiment 18: The average maximum concentration (C) of the pharmaceutical composition administered to the target was 75 ng / mL to 1200 ng / mL for GL0034. max A pharmaceutical composition according to any one of embodiments 1 to 16, which brings about ). Embodiment 19: The area under the concentration-time curve (AUC) of GL0034, administered to a subject at concentrations ranging from 6200 ng*h / mL to 406300 ng*h / mL over a 22-day period. 0-t A pharmaceutical composition according to any one of embodiments 1 to 16, which brings about ). Embodiment 20: The pharmaceutical composition according to Embodiment 16, wherein the dosage of the pharmaceutical composition includes 1520 μg, 2000 μg, or 2520 μg of GL0034. Embodiment 21: The average highest concentration (C) of the pharmaceutical composition administered to the target was 227 ng / mL to 367 ng / mL for GL0034. max The pharmaceutical composition according to Embodiment 20, which brings about ). Embodiment 22: The area under the concentration-time curve (AUC) of GL0034, administered to a subject at a concentration of 30313 ng*h / mL to 83082 ng*h / mL over a 22-day period. 0-t The pharmaceutical composition according to Embodiment 20, which brings about ). Embodiment 23: The administration of the pharmaceutical composition to the target subject is 90 to 120 hours, which is the plasma drug half-life (t) of GL0034. 1 / 2 A pharmaceutical composition according to any one of Embodiments 1 to 21, which brings about ). Embodiment 24: The administration of the pharmaceutical composition to the target subject corresponds to a plasma drug half-life (t) of GL0034, which is 98 to 113 hours. 1 / 2 The pharmaceutical composition according to Embodiment 21, which brings about ). Embodiment 25: The pharmaceutical composition is administered to a subject once a week or once every two weeks, as described in any one of Embodiments 1 to 12. Embodiment 26: The pharmaceutical composition is a pharmaceutical composition according to any one of Embodiments 1 to 12 or 25, wherein the dosage of the pharmaceutical composition includes 450 μg, 680 μg, 900 μg, 1520 μg, 2000 μg, or 2520 μg of GL0034. Embodiment 27: The pharmaceutical composition according to Embodiment 26, wherein the dosage of the pharmaceutical composition is administered once a week or once every two weeks. Embodiment 28: The dosage of the pharmaceutical composition contains 450 μg of GL0034, and the administration of the pharmaceutical composition to the subject once a week for at least 4 weeks results in an average peak concentration (C) of GL0034 of 101 ng / mL to 142 ng / mL. max The pharmaceutical composition according to embodiment 26, which brings about ). Embodiment 29: The area under the concentration-time curve (AUC) of GL0334, administered to a subject at a concentration of 12814 ng*h / mL to 18537 ng*h / mL over a 22-day period. 0-t The pharmaceutical composition according to Embodiment 28, which brings about ). Embodiment 30: The administration of the pharmaceutical composition to the subject resulted in a plasma drug half-life (t) of GL0034 of 102 hours by day 22. 1 / 2 The pharmaceutical composition according to Embodiment 28, which brings about ). Embodiment 31: The dosage of the pharmaceutical composition contains 680 μg of GL0034, and the administration of the pharmaceutical composition to the subject once a week for at least 4 weeks results in an average peak concentration (C) of GL0034 of 169 ng / mL to 267 ng / mL. max The pharmaceutical composition according to embodiment 26, which brings about ). Embodiment 32: The area under the concentration-time curve (AUC) of GL0034, administered to a subject at a concentration of 24576 ng*h / mL to 34537 ng*h / mL over a 22-day period. 0-t The pharmaceutical composition according to Embodiment 31, which brings about ). Embodiment 33: The administration of the pharmaceutical composition to the subject resulted in a plasma drug half-life (t) of GL0034 of 123 hours by day 22. 1 / 2 The pharmaceutical composition according to Embodiment 31, which brings about ). Embodiment 34: A pharmaceutical composition according to any one of Embodiments 1 to 12, wherein (i) a dose of the pharmaceutical composition containing 50 μg to 200 μg of GL0034 is administered to a subject once a week for at least two weeks; (ii) a dose of the pharmaceutical composition containing 200 μg to 400 μg of GL0034 is administered to a subject once a week for at least two weeks; (iii) a dose of the pharmaceutical composition containing 500 μg to 700 μg of GL0034 is administered to a subject once a week for at least two weeks; (iv) a dose of the pharmaceutical composition containing 1200 μg to 1500 μg of GL0034 is administered to a subject once a week for at least two weeks; and (v) a dose of the pharmaceutical composition containing 2000 μg to 3000 μg of GL0034 is administered to a subject once a week for at least four weeks. Embodiment 35: A pharmaceutical composition according to any one of Embodiments 1 to 12, wherein (i) a dose of the pharmaceutical composition containing 450 μg of GL0034 is administered to a subject once a week for at least two weeks, (ii) a dose of the pharmaceutical composition containing 900 μg of GL0034 is administered to a subject once a week for at least two weeks, and (iii) a dose of the pharmaceutical composition containing 1520 μg of GL0034 is administered to a subject once a week for at least four weeks. Embodiment 36: The average highest concentration (C) of the pharmaceutical composition administered to the target was 112 ng / mL to 708 ng / mL for GL0034. max The pharmaceutical composition according to Embodiment 35, which brings about ). Embodiment 37: The area under the concentration-time curve (AUC) of GL0034, administered to a subject at concentrations ranging from 12942 ng*h / mL to 76320 ng*h / mL over a 50-day period. 0-t The pharmaceutical composition according to Embodiment 35, which brings about ). Embodiment 38: The administration of the pharmaceutical composition to the subject resulted in a plasma drug half-life (t) of GL0034 of 106.8 ± 33.7 hours by day 50. 1 / 2 The pharmaceutical composition according to Embodiment 35, which brings about ). Embodiment 39: A pharmaceutical composition according to any one of Embodiments 1 to 12, wherein (i) an initial dose of a pharmaceutical composition containing 200 μg to 680 μg of GL0034 is administered to the subject for at least 4 weeks, (ii) an increasing dose of a pharmaceutical composition containing 680 μg to 900 μg of GL0034 is administered to the subject once a week for at least 2 weeks, and (iii) a maintenance dose of a pharmaceutical composition containing 1500 μg to 2000 μg of GL0034 is administered to the subject once a week for at least 2 weeks. Embodiment 40: (i) an initial dose of a pharmaceutical composition containing 450 μg to 680 μg of GL0034 is administered to the subject for at least 4 weeks, and (ii) an increasing dose of a pharmaceutical composition containing 680 μg to 900 μg of GL0034 is administered to the subject once a week for at least 2 weeks, according to any one of Embodiments 1 to 12. Embodiment 41: A pharmaceutical composition according to any one of Embodiments 1 to 12, wherein (i) an initial dose of a pharmaceutical composition containing 450 μg to 680 μg of GL0034 is administered to the subject for at least 4 weeks, (ii) an increasing dose of a pharmaceutical composition containing 680 μg to 900 μg of GL0034 is administered to the subject once a week for at least 2 weeks, and (iii) a maintenance dose of a pharmaceutical composition containing 1520 μg to 2000 μg of GL0034 is administered to the subject once a week for at least 2 weeks. Embodiment 42: The pharmaceutical composition according to any one of Embodiments 1 to 41, wherein administration of the pharmaceutical composition to a subject results in one or more clinically significant changes from baseline in the subject, the clinically significant changes from baseline being a decrease in alanine transaminase (ALT) levels, a decrease in aspartate aminotransferase (AST) levels, a decrease in gamma-glutamyltransferase (GGT) levels, a decrease in fasting insulin levels, a decrease in fasting blood glucose levels, a decrease in glycated hemoglobin (%HbA1c), a decrease in the homeostasis model assessment of insulin resistance (HOMA-IR), a decrease in body weight, a decrease in leptin levels, a decrease in triglyceride (TG) levels, a decrease in total cholesterol (TC) levels, a decrease in low-density lipoprotein (LDL) levels, an increase in high-density lipoprotein (HDL) levels, a decrease in the TG / HDL ratio, an increase in FGF-21 in the liver, an increase in uncoupling protein-1 (UCP-1) levels in brown adipose tissue (BAT) and / or white adipose tissue (WAT), and / or a decrease in blood pressure. Embodiment 43: The pharmaceutical composition according to Embodiment 42, wherein the reduction in ALT levels from baseline is sustained for at least 23 days, at least 52 days, or at least 78 days after administration of the pharmaceutical composition to the subject. Embodiment 44: (a) The change in ALT level from baseline is at least -9 U / L over a period of about 23 days after administration of a dose of the pharmaceutical composition containing 450 μg of GL0034 to the subject, or at least -3 U / L over a period of about 23 days after administration of a dose of the pharmaceutical composition containing 680 μg of GL0034 to the subject, or (b) The change in ALT level is at least -7 U / L over a period of about 51 days after the following administrations to the subject, or at least -1 U / L over a period of about 78 days, wherein the administrations are (i) a dose of the pharmaceutical composition containing 450 μg of GL0034 once a week for at least two weeks, (ii) a dose of the pharmaceutical composition containing 900 μg of GL0034 once a week for at least two weeks, and (iii) a dose of the pharmaceutical composition containing 1520 μg of GL0034 once a week for at least four weeks, according to Embodiment 42. Embodiment 45: The pharmaceutical composition according to Embodiment 42, wherein the reduction in AST levels from baseline is sustained for at least 23 days, at least 51 days, or at least 78 days after administration of the pharmaceutical composition to the subject. Embodiment 46: The pharmaceutical composition according to Embodiment 42, wherein the reduction in AST levels from baseline is at least -4 U / L over a period of approximately 51 days following the administration to the subject, or at least -1 U / L over a period of approximately 78 days, the administration being (i) a dose of the pharmaceutical composition containing 450 μg of GL0034 once a week for at least two weeks, (ii) a dose of the pharmaceutical composition containing 900 μg of GL0034 once a week for at least two weeks, and (iii) a dose of the pharmaceutical composition containing 1520 μg of GL0034 once a week for at least four weeks. Embodiment 47: The pharmaceutical composition according to Embodiment 42, wherein the reduction in GGT levels from baseline is sustained for at least 23 days, at least 51 days, or at least 78 days after administration of the pharmaceutical composition to the subject. Embodiment 48: The pharmaceutical composition according to Embodiment 42, wherein the change in GGT levels from baseline is at least -3 U / L over a period of approximately 51 days after the following administration to the subject, or at least -1 U / L over a period of approximately 78 days, the administration being (i) a dose of the pharmaceutical composition containing 450 μg of GL0034 once a week for at least two weeks, (ii) a dose of the pharmaceutical composition containing 900 μg of GL0034 once a week for at least two weeks, and (iii) a dose of the pharmaceutical composition containing 1520 μg of GL0034 once a week for at least four weeks. Embodiment 49: The pharmaceutical composition according to Embodiment 42, wherein the reduction in fasting insulin levels from baseline is sustained for at least 23 days, or at least 51 days, after administration of the pharmaceutical composition to the subject. Embodiment 50: The pharmaceutical composition according to Embodiment 42, wherein the change in fasting insulin levels from baseline is at least -5 pmol / L for a period of about 23 days after administration of 680 μg of GL0034 to the subject once a week for at least 4 weeks, or at least -11 pmol / L for a period of about 51 days after the following administrations to the subject, the administrations being (i) a dose of the pharmaceutical composition containing 450 μg of GL0034 once a week for at least 2 weeks, (ii) a dose of the pharmaceutical composition containing 900 μg of GL0034 once a week for at least 2 weeks, and (iii) a dose of the pharmaceutical composition containing 1520 μg of GL0034 once a week. Embodiment 51: The pharmaceutical composition according to Embodiment 42, wherein the reduction in fasting glucose persists for at least 23 days, or at least 51 days, after administration of the pharmaceutical composition to the subject. Embodiment 52: The pharmaceutical composition according to Embodiment 42, wherein the fasting glucose reduction is at least -3 mg / dL for a period of about 23 days after administration to a subject of a dose of the pharmaceutical composition containing 450 μg of GL0034 once a week for at least 4 weeks, or at least -5 mg / dL for a period of about 23 days after administration to a subject of a dose of the pharmaceutical composition containing 680 μg of GL0034 once a week for at least 4 weeks, or at least -8 mg / dL for a period of about 51 days after the following administrations to the subject, wherein the administrations are (i) a dose of the pharmaceutical composition containing 450 μg of GL0034 once a week for at least 2 weeks, (ii) a dose of the pharmaceutical composition containing 900 μg of GL0034 once a week for at least 2 weeks, and (iii) a dose of the pharmaceutical composition containing 1520 μg of GL0034 once a week for at least 4 weeks. Embodiment 53: The pharmaceutical composition according to Embodiment 42, wherein the weight loss is sustained for at least 8 days, at least 15 days, at least 22 days, at least 29 days, at least 50 days, at least 52 days, or at least 78 days after administration of the pharmaceutical composition to the subject. Embodiment 54: (a) Weight loss of at least -2 kg over a period of approximately 22 days following administration of a dose of the pharmaceutical composition containing 2000 μg of GL0034 to the subject; or at least -2 kg over a period of approximately 22 days following administration of a dose of the pharmaceutical composition containing 1520 μg of GL0034 to the subject; or at least -3 kg over a period of approximately 22 days following administration of a dose of the pharmaceutical composition containing 2520 μg of GL0034 to the subject; or at least -3 kg over a period of approximately 29 days following administration of a dose of the pharmaceutical composition containing 450 μg of GL0034 once a week for at least 4 weeks; or 680 μg once a week for at least 4 weeks. The pharmaceutical composition according to Embodiment 42, wherein (b) the weight loss is at least -4 kg over a period of about 29 days after administration of a dose of the pharmaceutical composition containing μg of GL0034 to a subject, or (b) the weight loss is at least -8 kg over a period of about 52 days after the following administration to the subject, or at least -6 kg over a period of about 78 days, wherein the administration is (i) a dose of the pharmaceutical composition containing 450 μg of GL0034 once a week for at least two weeks, (ii) a dose of the pharmaceutical composition containing 900 μg of GL0034 once a week for at least two weeks, and (iii) a dose of the pharmaceutical composition containing 1520 μg of GL0034 once a week for at least four weeks. Embodiment 55: The pharmaceutical composition according to Embodiment 42, wherein the reduction in leptin levels from baseline is dose-dependent. Embodiment 56: The pharmaceutical composition according to Embodiment 42, wherein the change in leptin levels from baseline is at least -7 ng / mL over a period of about 8 days after administration of a dose of the pharmaceutical composition containing 1520 μg of GL0034 to a subject, or at least -11 ng / mL over a period of about 8 days after administration of a dose of the pharmaceutical composition containing 2000 μg of GL0034 to a subject, or at least -12 ng / mL over a period of about 8 days after administration of a dose of the pharmaceutical composition containing 2520 μg of GL0034 to a subject. Embodiment 57: The pharmaceutical composition according to Embodiment 42, wherein a decrease in TG levels from baseline is observed on day 8 and persists for at least 51 days, or at least 78 days, after administration of the pharmaceutical composition to the subject. Embodiment 58: (a) The change in TG levels from baseline is at least -1 mmol / L over a period of about 8 days after administration of a dose of the pharmaceutical composition containing 2000 μg of GL0034 to a subject, or at least -1 mmol / L over a period of about 22 days after administration of a dose of the pharmaceutical composition containing 2520 μg of GL0034 to a subject, or (b) The change in TG levels is at least -21 mg / dL over a period of about 51 days after the following administrations to a subject, or at least -11 mg / dL over a period of about 78 days, wherein the administrations are (i) a dose of the pharmaceutical composition containing 450 μg of GL0034 once a week for at least two weeks, (ii) a dose of the pharmaceutical composition containing 900 μg of GL0034 once a week for at least two weeks, and (iii) a dose of the pharmaceutical composition containing 1520 μg of GL0034 once a week for at least four weeks, according to Embodiment 42. Embodiment 59: The pharmaceutical composition according to Embodiment 42, wherein the reduction in TC level from baseline is at least -29 mg / dL over a period of approximately 51 days after the following administration to the subject, or at least -6 mg / dL over a period of approximately 78 days, the administration being (i) a dose of the pharmaceutical composition containing 450 μg of GL0034 once a week for at least two weeks, (ii) a dose of the pharmaceutical composition containing 900 μg of GL0034 once a week for at least two weeks, and (iii) a dose of the pharmaceutical composition containing 1520 μg of GL0034 once a week for at least four weeks. Embodiment 60: The pharmaceutical composition according to Embodiment 42, wherein the change in LDL level from baseline is at least -24 mg / dL over a period of approximately 51 days after the following administration to the subject, or at least -20 mg / dL over a period of approximately 78 days, the administration being (i) a dose of the pharmaceutical composition containing 450 μg of GL0034 once a week for at least two weeks, (ii) a dose of the pharmaceutical composition containing 900 μg of GL0034 once a week for at least two weeks, and (iii) a dose of the pharmaceutical composition containing 1520 μg of GL0034 once a week for at least four weeks. Embodiment 61: The pharmaceutical composition according to Embodiment 42, wherein the increase in HDL levels from baseline is at least 3 mg / dL over a period of approximately 78 days following the administration to the subject, the administration being (i) a dose of the pharmaceutical composition containing 450 μg of GL0034 once a week for at least two weeks, (ii) a dose of the pharmaceutical composition containing 900 μg of GL0034 once a week for at least two weeks, and (iii) a dose of the pharmaceutical composition containing 1520 μg of GL0034 once a week for at least four weeks. Embodiment 62: The pharmaceutical composition according to Embodiment 42, wherein the clinically significant change from baseline in the subjects is a decrease in blood pressure. Embodiment 63: The pharmaceutical composition according to Embodiment 62, wherein the reduction in blood pressure is a reduction in systolic blood pressure. Embodiment 64: The pharmaceutical composition according to Embodiment 62, wherein the reduction in blood pressure is a reduction in diastolic blood pressure. Embodiment 65: The pharmaceutical composition according to Embodiment 63, wherein the reduction in systolic blood pressure from baseline is at least about 18 mmHg or at least about 14% over a period of about 23 days after administration to a subject of a dose of the pharmaceutical composition containing 450 μg of GL0034 once a week for at least 4 weeks. Embodiment 66: The pharmaceutical composition according to Embodiment 64, wherein the reduction in diastolic blood pressure from baseline is at least about 12 mmHg or at least about 14% over a period of about 23 days after administration to a subject of a dose of the pharmaceutical composition containing at least 450 μg of GL0034 once a week for at least 4 weeks. Embodiment 67: The pharmaceutical composition according to Embodiment 62, wherein the reduction in blood pressure in the subjects is greater than the reduction in blood pressure after administration of (a) 1.7 to 2.4 mg of semaglutide once a week, or (b) 5 to 15 mg of tilzepatide once a week. Embodiment 68: A pharmaceutical composition according to any one of Embodiments 1 to 67, wherein administration of the pharmaceutical composition to a subject results in a time-dependent decrease in the frequency of adverse events (AEs) in the subject. Embodiment 69: The pharmaceutical composition according to Embodiment 68, wherein the AE is one or more of nausea, vomiting, and / or loss of appetite. Embodiment 70: The pharmaceutical composition according to Embodiment 68, wherein the reduction in the frequency of AEs is dose-dependent. Embodiment 71: A pharmaceutical composition according to any one of Embodiments 1 to 12, wherein administration of a higher dose of the pharmaceutical composition to a subject does not result in an increase in severely therapeutic adverse events (TEAEs). Embodiment 72: A pharmaceutical composition comprising GL0034 for the treatment of hypertension in a subject, wherein a therapeutically effective dose of the pharmaceutical composition is administered to the subject. Embodiment 73: The pharmaceutical composition according to Embodiment 72, the target population is obese individuals. Embodiment 74: The subject is the pharmaceutical composition described in Embodiment 73, which is not for diabetes. Embodiment 75: The subject is the pharmaceutical composition according to Embodiment 72, which has metabolic disorders. Embodiment 76: The metabolic disorder is metabolic dysfunction-related fatty liver disease (MASLD), as described in Embodiment 75 of the pharmaceutical composition. Embodiment 77: The pharmaceutical composition according to Embodiment 76, wherein MASLD is metabolic disorder-associated steatohepatitis (MASH). Embodiment 78: The pharmaceutical composition according to Embodiment 75, wherein the metabolic disorder is diabetes mellitus or hypertriglyceridemia. Embodiment 79: The pharmaceutical composition according to Embodiment 78, wherein the metabolic disorder is type 2 diabetes. Embodiment 80: The pharmaceutical composition is administered subcutaneously to a subject, as described in any one of embodiments 72 to 79. Embodiment 81: The pharmaceutical composition is the pharmaceutical composition according to Embodiment 80, which is administered to a subject by subcutaneous injection. Embodiment 82: The pharmaceutical composition according to Embodiment 81, wherein the pharmaceutical composition is administered to a subject using an auto-injector or a pre-filled syringe. Embodiment 83: A pharmaceutical composition according to any one of Embodiments 72 to 82, wherein a dose of the pharmaceutical composition containing 450 μg of GL0034 is administered to a subject. Embodiment 84: The pharmaceutical composition according to Embodiment 83, wherein administration of the pharmaceutical composition results in a reduction of systolic blood pressure from baseline in a subject of at least about 18 mmHg or at least about 14% over a period of about 23 days after administration of the pharmaceutical composition. Embodiment 85: The pharmaceutical composition according to Embodiment 83, wherein administration of the pharmaceutical composition results in a reduction of diastolic blood pressure from baseline in a subject of at least about 12 mmHg or at least about 14% over a period of about 23 days after administration of the pharmaceutical composition. Embodiment 86: The pharmaceutical composition according to any one of Embodiments 72 to 85, wherein the reduction in blood pressure in the subject is greater than the reduction in blood pressure after administration of (a) 1.7 to 2.4 mg of semaglutide or (b) 5 to 15 mg of tilzepatide once a week. Embodiment 87: A method for treating obesity in a subject, comprising administering a therapeutically effective dose of GL0034 to the subject. Embodiment 88: The method described in Embodiment 87 is not applicable to patients with diabetes. Embodiment 89: The target group is individuals with a Body Mass Index (BMI) of at least 28 kg / m². 2 is either ≥27kg / m 2 The method according to either embodiment 87 or embodiment 88, wherein the person has at least one weight-related comorbidity. Embodiment 90: A method for treating metabolic disorders in a subject, comprising administering a therapeutically effective dose of GL0034 to the subject. Embodiment 91: The metabolic disorder is metabolic dysfunction-related fatty liver disease (MASLD), according to the method of Embodiment 90. Embodiment 92: The method according to Embodiment 91, wherein MASLD is metabolic disorder-associated steatohepatitis (MASH). Embodiment 93: The method according to embodiment 90, wherein the metabolic disorder is diabetes mellitus or hypertriglyceridemia. Embodiment 94: The metabolic disorder is type 2 diabetes, according to the method of embodiment 93. Embodiment 95: The subject is a person with hypertension and the method according to any one of embodiments 87 to 94. Embodiment 96: GL0034 is the method according to any one of embodiments 87 to 95, administered subcutaneously to the subject. Embodiment 97: GL0034 is the method according to Embodiment 96, administered to the subject by subcutaneous injection. Embodiment 98: GL0034 is administered to a subject using an auto-injector or a pre-filled syringe, according to the method of Embodiment 97. Embodiment 99: The method according to any one of embodiments 87 to 98, wherein a dose containing GL0034 in an amount of 200 μg to 8000 μg is administered to the subject. Embodiment 100: The dosage is as described in Embodiment 99, comprising 300 μg to 6000 μg of GL0034. Embodiment 101: The dosage is as described in Embodiment 100, containing 400 μg to 4000 μg of GL0034. Embodiment 102: The dosage is as described in Embodiment 101, containing 1000 μg to 3000 μg of GL0034. Embodiment 103: The dosage of GL0034 is administered to the subject once a week or once every two weeks, according to any one of embodiments 87 to 102. Embodiment 104: The administration of GL0034 to the subjects resulted in an average peak concentration of GL0034 (C) ranging from 75 ng / mL to 1200 ng / mL. max The method according to any one of embodiments 87 to 102, which brings about ). Embodiment 105: The area under the concentration-time curve (AUC) of GL0034 administered to a subject at concentrations ranging from 6200 ng*h / mL to 406300 ng*h / mL over a 22-day period. 0-t The method according to any one of embodiments 87 to 102, which brings about ). Embodiment 106: The dosage is as described in Embodiment 102, comprising 1520 μg, 2000 μg, or 2520 μg of GL0034. Embodiment 107: The administration of GL0034 to the subjects resulted in an average peak concentration of GL0034 (C) ranging from 227 ng / mL to 367 ng / mL. max The method according to embodiment 106, which brings about ). Embodiment 108: The area under the concentration-time curve (AUC) of GL0034 administered to subjects at concentrations ranging from 30313 ng*h / mL to 83082 ng*h / mL over a 22-day period. 0-tThe method according to embodiment 106, which brings about ). Embodiment 109: The administration of GL0034 to the target subject corresponds to a plasma drug half-life (t) of GL0034, which is 90 to 120 hours. 1 / 2 The method according to any one of embodiments 87 to 107, which brings about ). Embodiment 110: The administration of GL0034 to the subject was within 98 to 113 hours, which is the plasma drug half-life (t 1 / 2 The method according to embodiment 107, which brings about ). Embodiment 111: GL0034 is administered to the subject once a week or once every two weeks, according to any one of embodiments 87 to 98. Embodiment 112: The method according to any one of Embodiments 87-98 or 111, wherein a dose containing GL0034 in amounts of 450 μg, 680 μg, 900 μg, 1520 μg, 2000 μg, or 2520 μg is administered to the subject. Embodiment 113: The dosage of GL0034 is administered to the subject once a week or once every two weeks, as described in Embodiment 112. Embodiment 114: GL0034 was administered to subjects at a dose of 450 μg once a week for at least 4 weeks, and the mean peak concentration (C) of GL0034 was measured. max The method according to Embodiment 112, wherein the concentration is 101 ng / mL to 142 ng / mL. Embodiment 115: The area under the concentration-time curve (AUC) of GL0034 administered to subjects at concentrations of 12814 ng*h / mL to 18537 ng*h / mL over a 22-day period. 0-t The method according to embodiment 114, which brings about ). Embodiment 116: Administration of GL0034 to the subjects resulted in a plasma drug half-life (t) of GL0034 of 102 hours by day 22. 1 / 2 The method according to embodiment 114, which brings about ). Embodiment 117: GL0034 was administered to subjects at a dose of 680 μg once a week for at least 4 weeks, and the mean peak concentration (C) of GL0034 was measured. max The method according to Embodiment 112, wherein the ng / mL is 169 ng / mL to 267 ng / mL. Embodiment 118: The area under the concentration-time curve (AUC) of GL0034 administered to subjects at concentrations of 24576 ng*h / mL to 34537 ng*h / mL over a 22-day period. 0-t The method according to embodiment 117, which brings about ). Embodiment 119: Administration of GL0034 to the subjects resulted in a plasma drug half-life (t) of GL0034 of 123 hours by day 22. 1 / 2 The method according to embodiment 117, which brings about ). Embodiment 120: The method according to any one of Embodiments 87 to 98, wherein (i) GL0034 is administered to the subject once a week for at least two weeks at a dose of 50 μg to 200 μg, (ii) GL0034 is administered to the subject once a week for at least two weeks at a dose of 200 μg to 400 μg, (iii) GL0034 is administered to the subject once a week for at least two weeks at a dose of 500 μg to 700 μg, (iv) GL0034 is administered to the subject once a week for at least two weeks at a dose of 1200 μg to 1500 μg, and (v) GL0034 is administered to the subject once a week for at least four weeks at a dose of 2000 μg to 3000 μg. Embodiment 121: (i) GL0034 is administered to the subject at a dose of 450 μg once a week for at least two weeks; (ii) GL0034 is administered to the subject at a dose of 900 μg once a week for at least two weeks; (iii) GL0034 is administered to the subject at a dose of 1520 μg once a week for at least four weeks, according to any one of embodiments 87 to 98. Embodiment 122: The administration of GL0034 to the subjects resulted in an average peak concentration of GL0034 (C) ranging from 112 ng / mL to 708 ng / mL. maxThe method according to Embodiment 121, which brings about ). Embodiment 123: The area under the concentration-time curve (AUC) of GL0034 administered to subjects at concentrations ranging from 12942 ng*h / mL to 76320 ng*h / mL over a 50-day period. 0-t The method according to Embodiment 121, which brings about ). Embodiment 124: Administration of GL0034 to the subjects resulted in a plasma drug half-life (t) of GL0034 of 106.8 ± 33.7 hours by day 50. 1 / 2 The method according to Embodiment 121, which brings about ). Embodiment 125: The method according to any one of Embodiments 87 to 98, comprising: (i) administering an initial dose containing 200 μg to 680 μg of GL0034 for at least 4 weeks; (ii) administering an escalating dose containing 680 μg to 900 μg of GL0034 once a week for at least 2 weeks; and (iii) administering a maintenance dose containing 1500 μg to 2000 μg of GL0034 once a week for at least 2 weeks. Embodiment 126: The method according to any one of Embodiments 87 to 98, comprising (i) administering an initial dose containing 450 μg to 680 μg of GL0034 for a period of 4 weeks, and (ii) administering an escalating dose containing 680 μg to 900 μg of GL0034 once a week for at least 2 weeks. Embodiment 127: The method according to any one of Embodiments 87 to 98, comprising: (i) administering an initial dose containing 450 μg to 680 μg of GL0034 for 4 weeks; (ii) administering an escalating dose containing 680 μg to 900 μg of GL0034 once a week for at least 2 weeks; and (iii) administering a maintenance dose containing 1520 μg to 2000 μg of GL0034 once a week for at least 2 weeks. Embodiment 128: The method according to any one of Embodiments 87 to 127, wherein administration of GL0034 to a subject results in one or more clinically significant changes from baseline in the subject, the clinically significant changes from baseline being a decrease in alanine transaminase (ALT) levels, a decrease in aspartate aminotransferase (AST) levels, a decrease in gamma-glutamyltransferase (GGT) levels, a decrease in fasting insulin levels, a decrease in fasting blood glucose levels, a decrease in glycated hemoglobin (%HbA1c), a decrease in the homeostasis model assessment of insulin resistance (HOMA-IR), a decrease in body weight, a decrease in leptin levels, a decrease in triglyceride (TG) levels, a decrease in total cholesterol (TC) levels, a decrease in low-density lipoprotein (LDL) levels, an increase in high-density lipoprotein (HDL) levels, a decrease in the TG / HDL ratio, an increase in FGF-21 in the liver, an increase in uncoupling protein-1 (UCP-1) levels in brown adipose tissue (BAT) and / or white adipose tissue (WAT), and / or a decrease in blood pressure. Embodiment 129: The method according to Embodiment 128, wherein the reduction in ALT levels from baseline is sustained for at least 23 days, at least 52 days, or at least 78 days after administration of GL0034 to the subject. Embodiment 130: The method according to Embodiment 128, wherein (a) the change in ALT level from baseline is at least -9 U / L over a period of about 23 days after administration of a dose containing 450 μg of GL0034 to a subject, or at least -3 U / L over a period of about 23 days after administration of a dose containing 680 μg of GL0034 to a subject, or (b) the change in ALT level is at least -7 U / L over a period of about 51 days after the following administrations to a subject, or at least -1 U / L over a period of about 78 days, wherein the administrations are (i) a dose containing 450 μg of GL0034 once a week for at least two weeks, (ii) a dose containing 900 μg of GL0034 once a week for at least two weeks, and (iii) a dose containing 1520 μg of GL0034 once a week for at least four weeks. Embodiment 131: The method according to Embodiment 128, wherein the reduction in AST levels from baseline is sustained for at least 23 days, at least 51 days, or at least 78 days after administration of GL0034 to the subject. Embodiment 132: The method according to Embodiment 128, wherein the change in AST levels from baseline is at least -4 U / L over a period of approximately 51 days after the administration to the subject, or at least -1 U / L over a period of approximately 78 days, the administration being (i) a dose containing 450 μg of GL0034 once a week for at least two weeks, (ii) a dose containing 900 μg of GL0034 once a week for at least two weeks, and (iii) a dose containing 1520 μg of GL0034 once a week for at least four weeks. Embodiment 133: The method according to Embodiment 128, wherein the reduction in GGT levels from baseline is sustained for at least 23 days, at least 51 days, or at least 78 days after administration of GL0034 to the subject. Embodiment 134: The method according to Embodiment 128, wherein the change in GGT levels from baseline is at least -3 U / L over a period of approximately 51 days following the administration to the subject, or at least -1 U / L over a period of approximately 78 days, the administration being (i) a dose containing 450 μg of GL0034 once a week for at least two weeks, (ii) a dose containing 900 μg of GL0034 once a week for at least two weeks, and (iii) a dose containing 1520 μg of GL0034 once a week for at least four weeks. Embodiment 135: The method according to Embodiment 128, wherein the reduction in fasting insulin levels from baseline persists for at least 23 days or at least 51 days after administration of GL0034 to the subject. Embodiment 136: The method according to Embodiment 128, wherein the change in fasting insulin levels from baseline is at least -5 pmol / L for a period of about 23 days after administration to a subject with a dose containing 680 μg of GL0034 once weekly for at least 4 weeks, or at least -11 pmol / L for a period of about 51 days after the administration to the subject, the doses being (i) a dose containing 450 μg of GL0034 once weekly for at least 2 weeks, (ii) a dose containing 900 μg of GL0034 once weekly for at least 2 weeks, and (iii) a dose containing 1520 μg of GL0034 once weekly for at least 4 weeks. Embodiment 137: The method according to Embodiment 128, wherein the reduction in fasting glucose persists for at least 23 days or at least 51 days after administration of GL0034 to the subject. Embodiment 138: The method according to Embodiment 128, wherein the fasting glucose reduction is at least -3 mg / dL for a period of about 23 days after administration of a dose containing 450 μg of GL0034 once weekly to a subject for at least 4 weeks, or at least -5 mg / dL for a period of about 23 days after administration of a dose containing 680 μg of GL0034 once weekly to a subject for at least 4 weeks, or at least -8 mg / dL for a period of about 51 days after the following administrations to the subject, the administrations being (i) a dose containing 450 μg of GL0034 once weekly for at least 2 weeks, (ii) a dose containing 900 μg of GL0034 once weekly for at least 2 weeks, and (iii) a dose containing 1520 μg of GL0034 once weekly for at least 4 weeks. Embodiment 139: The method according to Embodiment 128, wherein the weight loss is sustained for at least 8 days, at least 15 days, at least 22 days, at least 29 days, at least 50 days, at least 52 days, or at least 78 days after administration of GL0034 to the subject. Embodiment 140: (a) Weight loss of at least -2 kg over a period of approximately 22 days following administration of a dose containing 2000 μg of GL0034 to the subject; or at least -2 kg over a period of approximately 22 days following administration of a dose containing 1520 μg of GL0034 to the subject; or at least -3 kg over a period of approximately 22 days following administration of a dose containing 2520 μg of GL0034 to the subject; or at least -3 kg over a period of approximately 29 days following administration of a dose containing 450 μg of GL0034 once a week for at least 4 weeks; or 68 once a week for at least 4 weeks. The method according to Embodiment 128, wherein (b) the weight loss is at least -4 kg over a period of about 29 days after administration of a dose containing 0 μg of GL0034 to the subject, or (b) the weight loss is at least -8 kg over a period of about 52 days after the following administrations to the subject, or at least -6 kg over a period of about 78 days, wherein the administrations are (i) a dose containing 450 μg of GL0034 once a week for at least two weeks, (ii) a dose containing 900 μg of GL0034 once a week for at least two weeks, and (iii) a dose containing 1520 μg of GL0034 once a week for at least four weeks. Embodiment 141: The method according to Embodiment 128, wherein the reduction in leptin levels from baseline is dose-dependent. Embodiment 142: The method according to Embodiment 128, wherein the change in leptin levels from baseline is at least -7 ng / mL over a period of approximately 8 days after administration of a dose containing 1520 μg of GL0034 to a subject, or at least -11 ng / mL over a period of approximately 8 days after administration of a dose containing 2000 μg of GL0034 to a subject, or at least -12 ng / mL over a period of approximately 8 days after administration of a dose containing 2520 μg of GL0034 to a subject. Embodiment 143: The method according to Embodiment 128, wherein a decrease in TG levels from baseline is observed on day 8 and persists for at least 51 days or at least 78 days after administration of GL0034 to the subject. Embodiment 144: The method according to Embodiment 128, wherein (a) the change in TG levels from baseline is at least -1 mmol / L over a period of about 8 days after administration of a dose containing 2000 μg of GL0034 to a subject, or at least -1 mmol / L over a period of about 22 days after administration of a dose containing 2520 μg of GL0034, or (b) the change in TG levels is at least -21 mg / dL over a period of about 51 days after the following administrations to a subject, or at least -11 mg / dL over a period of about 78 days, wherein the administrations are (i) a dose containing 450 μg of GL0034 once a week for at least two weeks, (ii) a dose containing 900 μg of GL0034 once a week for at least two weeks, and (iii) a dose containing 1520 μg of GL0034 once a week for at least four weeks. Embodiment 145: The method according to Embodiment 128, wherein the reduction in TC level from baseline is at least -29 mg / dL over a period of approximately 51 days following the administration to the subject, or at least -6 mg / dL over a period of approximately 78 days, the administration being (i) a dose containing 450 μg of GL0034 once a week for at least two weeks, (ii) a dose containing 900 μg of GL0034 once a week for at least two weeks, and (iii) a dose containing 1520 μg of GL0034 once a week for at least four weeks. Embodiment 146: The method according to Embodiment 128, wherein the change in LDL level from baseline is at least -24 mg / dL over a period of approximately 51 days after the administration to the subject, or at least -20 mg / dL over a period of approximately 78 days, the administration being (i) a dose containing 450 μg of GL0034 once a week for at least two weeks, (ii) a dose containing 900 μg of GL0034 once a week for at least two weeks, and (iii) a dose containing 1520 μg of GL0034 once a week for at least four weeks. Embodiment 147: The method according to Embodiment 128, wherein the increase in HDL levels from baseline is at least 3 mg / dL over a period of approximately 78 days following the administration to the subject, the administration being (i) a dose containing 450 μg of GL0034 once a week for at least two weeks, (ii) a dose containing 900 μg of GL0034 once a week for at least two weeks, and (iii) a dose containing 1520 μg of GL0034 once a week for at least four weeks. Embodiment 148: The clinically significant change from baseline in the subjects is a decrease in blood pressure, according to the method of Embodiment 128. Embodiment 149: The method according to Embodiment 148, wherein the reduction in blood pressure is a reduction in systolic blood pressure. Embodiment 150: The method according to Embodiment 148, wherein the reduction in blood pressure is a reduction in diastolic blood pressure. Embodiment 151: The method according to Embodiment 149, wherein the reduction in systolic blood pressure from baseline is at least about 18 mmHg or at least about 14% over a period of about 23 days after administration of a dose containing 450 μg of GL0034 once a week to a subject for at least 4 weeks. Embodiment 152: The method according to Embodiment 150, wherein the reduction in diastolic blood pressure from baseline is at least about 12 mmHg or at least about 14% over a period of about 23 days after administration to a subject with a dose containing at least 450 μg of GL0034 once a week for at least 4 weeks. Embodiment 153: The method according to Embodiment 148, wherein the reduction in blood pressure in the subjects is greater than the reduction in blood pressure after administration of (a) 1.7-2.4 mg of semaglutide once a week, or (b) 5-15 mg of tilzepatide once a week. Embodiment 154: The method according to any one of embodiments 87 to 153, wherein administration of GL0034 to a subject results in a time-dependent decrease in the frequency of adverse events (AEs) in the subject. Embodiment 155: The method according to Embodiment 154, wherein the AE is one or more of nausea, vomiting, and / or loss of appetite. Embodiment 156: The reduction in the frequency of AEs is dose-dependent, as described in Embodiment 154. Embodiment 157: The method according to any one of embodiments 87 to 98, wherein administering a higher dose of GL0034 to the subject does not result in an increase in severely therapeutic adverse events (TEAEs). Embodiment 158: A method for treating hypertension in a subject, comprising administering a therapeutically effective dose of GL0034 to the subject. Embodiment 159: The method according to embodiment 158, wherein the subject is obese. Embodiment 160: The method described in Embodiment 159 is not applicable to patients with diabetes. Embodiment 161: The subject is the method according to Embodiment 158, which applies to individuals with metabolic disorders. Embodiment 162: The metabolic disorder is metabolic dysfunction-related fatty liver disease (MASLD), according to the method of Embodiment 161. Embodiment 163: The method according to Embodiment 162, wherein MASLD is metabolic disorder-associated steatohepatitis (MASH). Embodiment 164: The method according to Embodiment 161, wherein the metabolic disorder is diabetes mellitus or hypertriglyceridemia. Embodiment 165: The metabolic disorder is type 2 diabetes, according to the method of embodiment 164. Embodiment 166: GL0034 is the method according to any one of embodiments 158 to 165, administered subcutaneously to the subject. Embodiment 167: GL0034 is the method according to Embodiment 166, administered to the subject by subcutaneous injection. Embodiment 168: GL0034 is administered to a subject using an auto-injector or a pre-filled syringe, according to the method of Embodiment 167. Embodiment 169: The method according to any one of Embodiments 158 to 168, wherein a dose containing 450 μg of GL0034 is administered to the subject. Embodiment 170: The method according to Embodiment 169, wherein administration of GL0034 results in a reduction of systolic blood pressure from baseline in subjects of at least about 18 mmHg or at least about 14% over a period of about 23 days following administration of GL0034. Embodiment 171: The method according to Embodiment 169, wherein administration of GL0034 results in a reduction of diastolic blood pressure from baseline in subjects of at least about 12 mmHg or at least about 14% over a period of about 23 days following administration of GL0034. Embodiment 172: The method according to any one of Embodiments 158 to 171, wherein the reduction in blood pressure in the subjects is greater than the reduction in blood pressure after administration of (a) 1.7 to 2.4 mg of semaglutide or (b) 5 to 15 mg of tilzepatide once a week. Embodiment 173: Use of GL0034 for the manufacture of drugs for treating obesity in a subject. Embodiment 174: The subject is not diabetes, and the use is as described in Embodiment 173. Embodiment 175: The target group is individuals with a Body Mass Index (BMI) of at least 28 kg / m². 2 is either ≥27kg / m 2 The use according to either Embodiment 173 or Embodiment 174, wherein the patient has at least one weight-related comorbidity. Embodiment 176: Use of GL0034 for the manufacture of drugs for treating metabolic disorders in subjects. Embodiment 177: The metabolic disorder is metabolic dysfunction-associated fatty liver disease (MASLD), as described in Embodiment 176. Embodiment 178: MASLD is metabolic disorder-associated steatohepatitis (MASH), as described in Embodiment 177. Embodiment 179: The metabolic disorder is diabetes or hypertriglyceridemia, as described in Embodiment 176. Embodiment 180: The metabolic disorder is type 2 diabetes, as described in Embodiment 179. Embodiment 181: The target population is individuals with hypertension, and the use described in any one of embodiments 173 to 180 applies to them. Embodiment 182: The drug is administered subcutaneously to the subject, as described in any one of Embodiments 173 to 181. Embodiment 183: The drug is administered to the subject by subcutaneous injection, as described in Embodiment 182. Embodiment 184: The drug is administered to the subject using an auto-injector or a pre-filled syringe, as described in Embodiment 183. Embodiment 185: The dosage of the drug is 200 μg to 8000 μg of GL0034, as described in any one of Embodiments 173 to 184. Embodiment 186: The dosage of the drug is as described in Embodiment 185, containing 300 μg to 6000 μg of GL0034. Embodiment 187: The dosage of the drug is as described in Embodiment 186, containing 400 μg to 4000 μg of GL0034. Embodiment 188: The dosage of the drug is as described in Embodiment 187, containing 1000 μg to 3000 μg of GL0034. Embodiment 189: The dosage of the drug is administered to the subject once a week or once every two weeks, as described in any one of Embodiments 173 to 188. Embodiment 190: The average highest concentration (C) of GL0034 administered to the target group was 75 ng / mL to 1200 ng / mL.max The use described in any one of embodiments 173 to 188 brings about the result of the use described in any one of embodiments 173 to 188. Embodiment 191: The area under the concentration-time curve (AUC) of GL0034, administered to the subject at concentrations ranging from 6200 ng*h / mL to 406300 ng*h / mL over a 22-day period. 0-t The use described in any one of embodiments 173 to 188 brings about the result of the use described in any one of embodiments 173 to 188. Embodiment 192: The drug dosage is 1520 μg, 2000 μg, or 2520 μg of GL0034, as described in Embodiment 188. Embodiment 193: The average highest concentration (C) of GL0034 administered to the subjects was 227 ng / mL to 367 ng / mL. max The use described in Embodiment 192 brings about the following: Embodiment 194: The area under the concentration-time curve (AUC) of GL0034 administered to the subject at a concentration of 30313 ng*h / mL to 83082 ng*h / mL over a 22-day period. 0-t The use described in Embodiment 192 brings about the following: Embodiment 195: The administration of the drug to the target subject corresponds to a plasma drug half-life (t) of GL0034, which is 90 to 120 hours. 1 / 2 The use described in any one of embodiments 173 to 193 brings about the result of the use described in any one of embodiments 173 to 193. Embodiment 196: The administration of the drug to the target subject corresponds to a plasma drug half-life (t) of GL0034, which is 98 to 113 hours. 1 / 2 The use described in Embodiment 193 brings about the following: Embodiment 197: The drug is administered to the subject once a week or once every two weeks, as described in any one of Embodiments 173 to 184. Embodiment 198: The drug dosage is 450 μg, 680 μg, 900 μg, 1520 μg, 2000 μg, or 2520 μg of GL0034, as described in any one of Embodiments 173-184 or 197. Embodiment 199: The dosage of the drug is administered once a week or once every two weeks, as described in Embodiment 198. Embodiment 200: The drug dosage includes 450 μg of GL0034, administered to the subject once a week for at least 4 weeks, resulting in an average peak concentration (C) of GL0034 between 101 ng / mL and 142 ng / mL. max The use described in Embodiment 198 brings about the following: Embodiment 201: The area under the concentration-time curve (AUC) of GL0334 administered to the subject at a concentration of 12814 ng*h / mL to 18537 ng*h / mL over a 22-day period. 0-t The use described in Embodiment 200 brings about the following: Embodiment 202: The administration of the drug to the subjects by day 22 showed that the plasma drug half-life of GL0034 was 102 hours (t 1 / 2 The use described in Embodiment 200 brings about the following: Embodiment 203: The drug dose is 680 μg of GL0034, administered to the subject once a week for at least 4 weeks, resulting in an average peak concentration (C) of GL0034 between 169 ng / mL and 267 ng / mL. max The use described in Embodiment 198 brings about the following: Embodiment 204: The area under the concentration-time curve (AUC) of GL0034 administered to the subject at a concentration of 24576 ng*h / mL to 34537 ng*h / mL over a 22-day period. 0-t The use described in Embodiment 203 brings about the following: Embodiment 205: The administration of the drug to the subjects by day 22 had a plasma drug half-life (t) of GL0034 of 123 hours. 1 / 2 The use described in Embodiment 203 brings about the following: Embodiment 206: The use according to any one of Embodiments 173 to 184, wherein (i) a dose of the drug containing 50 μg to 200 μg of GL0034 is administered to the subject once a week for at least two weeks, (ii) a dose of the drug containing 200 μg to 400 μg of GL0034 is administered to the subject once a week for at least two weeks, (iii) a dose of the drug containing 500 μg to 700 μg of GL0034 is administered to the subject once a week for at least two weeks, (iv) a dose of the drug containing 1200 μg to 1500 μg of GL0034 is administered to the subject once a week for at least two weeks, and (v) a dose of the drug containing 2000 μg to 3000 μg of GL0034 is administered to the subject once a week for at least four weeks. Embodiment 207: The use according to any one of Embodiments 173 to 184, wherein (i) a dose of the drug containing 450 μg of GL0034 is administered to the subject once a week for at least two weeks, (ii) a dose of the drug containing 900 μg of GL0034 is administered to the subject once a week for at least two weeks, and (iii) a dose of the drug containing 1520 μg of GL0034 is administered to the subject once a week for at least four weeks. Embodiment 208: The average highest concentration (C) of GL0034 administered to the subjects was 112 ng / mL to 708 ng / mL. max The use described in Embodiment 207 brings about the following: Embodiment 209: The area under the concentration-time curve (AUC) of GL0034 administered to the subject at a concentration of 12942 ng*h / mL to 76320 ng*h / mL over a 50-day period. 0-t The use described in Embodiment 207 brings about the following: Embodiment 210: The administration of the drug to the subjects by day 50 resulted in a plasma drug half-life (t) of GL0034 of 106.8 ± 33.7 hours. 1 / 2 The use described in Embodiment 207 brings about the following: Embodiment 211: The use according to any one of Embodiments 173 to 184, wherein (i) an initial dose of a drug containing GL0034 in an amount of 200 μg to 680 μg is administered to the subject for at least 4 weeks, (ii) an escalating dose of a drug containing GL0034 in an amount of 680 μg to 900 μg is administered to the subject once a week for at least 2 weeks, and (iii) a maintenance dose of a drug containing GL0034 in an amount of 1500 μg to 2000 μg is administered to the subject once a week for at least 2 weeks. Embodiment 212: The use according to any one of Embodiments 173 to 184, wherein (i) an initial dose of a drug containing 450 μg to 680 μg of GL0034 is administered to the subject for at least 4 weeks, and (ii) an increasing dose of a drug containing 680 μg to 900 μg of GL0034 is administered to the subject once a week for at least 2 weeks. Embodiment 213: The use according to any one of Embodiments 173 to 184, wherein (i) an initial dose of a drug containing 450 μg to 680 μg of GL0034 is administered to the subject for at least 4 weeks, (ii) an escalating dose of a drug containing 680 μg to 900 μg of GL0034 is administered to the subject once a week for at least 2 weeks, and (iii) a maintenance dose of a drug containing 1520 μg to 2000 μg of GL0034 is administered to the subject once a week for at least 2 weeks. Embodiment 214: The use according to any one of Embodiments 173 to 213, wherein administration of the drug to the subject results in one or more clinically significant changes from baseline in the subject, the clinically significant changes from baseline being a decrease in alanine transaminase (ALT) levels, a decrease in aspartate aminotransferase (AST) levels, a decrease in gamma-glutamyltransferase (GGT) levels, a decrease in fasting insulin levels, a decrease in fasting blood glucose levels, a decrease in glycated hemoglobin (%HbA1c), a decrease in the homeostasis model assessment of insulin resistance (HOMA-IR), a decrease in body weight, a decrease in leptin levels, a decrease in triglyceride (TG) levels, a decrease in total cholesterol (TC) levels, a decrease in low-density lipoprotein (LDL) levels, an increase in high-density lipoprotein (HDL) levels, a decrease in the TG / HDL ratio, an increase in FGF-21 in the liver, an increase in uncoupling protein-1 (UCP-1) levels in brown adipose tissue (BAT) and / or white adipose tissue (WAT), and / or a decrease in blood pressure. Embodiment 215: The use according to Embodiment 214, wherein the reduction in ALT levels from baseline is sustained for at least 23 days, at least 52 days, or at least 78 days after administration of the drug to the subject. Embodiment 216: (a) The change in ALT level from baseline is at least -9 U / L over a period of approximately 23 days after administration of a dose of the drug containing 450 μg of GL0034 to the subject, or at least -3 U / L over a period of approximately 23 days after administration of a dose of the drug containing 680 μg of GL0034 to the subject, or (b) The change in ALT level is at least -7 U / L over a period of approximately 51 days after the following administrations to the subject, or at least -1 U / L over a period of approximately 78 days, wherein the administrations are (i) a dose of the drug containing 450 μg of GL0034 once a week for at least two weeks, (ii) a dose of the drug containing 900 μg of GL0034 once a week for at least two weeks, and (iii) a dose of the drug containing 1520 μg of GL0034 once a week for at least four weeks, as described in Embodiment 214. Embodiment 217: The use according to Embodiment 214, wherein the reduction in AST levels from baseline is sustained for at least 23 days, at least 51 days, or at least 78 days after administration of the drug to the subject. Embodiment 218: The use according to Embodiment 214, wherein the change in AST levels from baseline is at least -4 U / L over a period of approximately 51 days following the administration to the subject, or at least -1 U / L over a period of approximately 78 days, the administration being (i) a dose of the drug containing 450 μg of GL0034 once a week for at least two weeks, (ii) a dose of the drug containing 900 μg of GL0034 once a week for at least two weeks, and (iii) a dose of the drug containing 1520 μg of GL0034 once a week for at least four weeks. Embodiment 219: The use according to Embodiment 214, wherein the reduction in GGT levels from baseline is sustained for at least 23 days, at least 51 days, or at least 78 days after administration of the drug to the subject. Embodiment 220: The use according to Embodiment 214, wherein the change in GGT levels from baseline is at least -3 U / L over a period of approximately 51 days following the administration to the subject, or at least -1 U / L over a period of approximately 78 days, the administration being (i) a dose of the drug containing 450 μg of GL0034 once a week for at least two weeks, (ii) a dose of the drug containing 900 μg of GL0034 once a week for at least two weeks, and (iii) a dose of the drug containing 1520 μg of GL0034 once a week for at least four weeks. Embodiment 221: The use according to Embodiment 214, wherein the reduction in fasting insulin levels from baseline persists for at least 23 days or at least 51 days after administration of the drug to the subject. Embodiment 222: The use according to Embodiment 214, wherein the change in fasting insulin levels from baseline is at least -5 pmol / L for a period of approximately 23 days after administration of 680 μg of GL0034 once weekly to the subject for at least 4 weeks, or at least -11 pmol / L for a period of approximately 51 days after the following administrations to the subject, the administrations being (i) a dose of the drug containing 450 μg of GL0034 once weekly for at least 2 weeks, (ii) a dose of the drug containing 900 μg of GL0034 once weekly for at least 2 weeks, and (iii) a dose of the drug containing 1520 μg of GL0034 once weekly for at least 4 weeks. Embodiment 223: The use according to Embodiment 214, wherein the reduction in fasting glucose persists for at least 23 days or at least 51 days after administration of the drug to the subject. Embodiment 224: The use according to Embodiment 214, wherein the reduction in fasting glucose is at least -3 mg / dL for a period of about 23 days after administration to a subject of a drug dose containing 450 μg of GL0034 once weekly for at least 4 weeks, or at least -5 mg / dL for a period of about 23 days after administration to a subject of a drug dose containing 680 μg of GL0034 once weekly for at least 4 weeks, or at least -8 mg / dL for a period of about 51 days after the following administrations to the subject, the administrations being (i) a drug dose containing 450 μg of GL0034 once weekly for at least 2 weeks, (ii) a drug dose containing 900 μg of GL0034 once weekly for at least 2 weeks, and (iii) a drug dose containing 1520 μg of GL0034 once weekly for at least 4 weeks. Embodiment 225: The use according to Embodiment 214, wherein the weight loss persists for at least 8 days, at least 15 days, at least 22 days, at least 29 days, at least 50 days, at least 52 days, or at least 78 days after administration of the drug to the subject. Embodiment 226: (a) Weight loss of at least -2 kg over a period of approximately 22 days following administration of a dose of the drug containing 2000 μg of GL0034 to the subject; or at least -2 kg over a period of approximately 22 days following administration of a dose of the drug containing 1520 μg of GL0034 to the subject; or at least -3 kg over a period of approximately 22 days following administration of a dose of the drug containing 2520 μg of GL0034 to the subject; or at least -3 kg over a period of approximately 29 days following administration of a dose of the drug containing 450 μg of GL0034 once a week for at least 4 weeks; or 68 once a week for at least 4 weeks. The use according to Embodiment 214, wherein (b) the weight loss is at least -4 kg over a period of about 29 days after administration of a dose of the drug containing 0 μg of GL0034 to the subject, or (b) the weight loss is at least -8 kg over a period of about 52 days after the following administrations to the subject, or at least -6 kg over a period of about 78 days, wherein the administrations are (i) a dose of the drug containing 450 μg of GL0034 once a week for at least two weeks, (ii) a dose of the drug containing 900 μg of GL0034 once a week for at least two weeks, and (iii) a dose of the drug containing 1520 μg of GL0034 once a week for at least four weeks. Embodiment 227: The reduction in leptin levels from baseline is dose-dependent, as described in Embodiment 214. Embodiment 228: The use according to Embodiment 214, wherein the change in leptin levels from baseline is at least -7 ng / mL over a period of approximately 8 days after administration of a dose of the drug containing 1520 μg of GL0034 to the subject, or at least -11 ng / mL over a period of approximately 8 days after administration of a dose of the drug containing 2000 μg of GL0034 to the subject, or at least -12 ng / mL over a period of approximately 8 days after administration of a dose of the drug containing 2520 μg of GL0034 to the subject. Embodiment 229: The use according to Embodiment 214, in which a decrease in TG levels from baseline is observed on day 8 and persists for at least 51 days or at least 78 days after administration of the drug to the subject. Embodiment 230: (a) The change in TG levels from baseline is at least -1 mmol / L over a period of about 8 days after administration of a dose of the drug containing 2000 μg of GL0034 to the subject, or at least -1 mmol / L over a period of about 22 days after administration of a dose of the drug containing 2520 μg of GL0034 to the subject, or (b) The change in TG levels is at least -21 mg / dL over a period of about 51 days after the following administrations to the subject, or at least -11 mg / dL over a period of about 78 days, wherein the administrations are (i) a dose of the drug containing 450 μg of GL0034 once a week for at least two weeks, (ii) a dose of the drug containing 900 μg of GL0034 once a week for at least two weeks, and (iii) a dose of the drug containing 1520 μg of GL0034 once a week for at least four weeks, as described in Embodiment 214. Embodiment 231: The use according to Embodiment 214, wherein the reduction in TC level from baseline is at least -29 mg / dL over a period of approximately 51 days following the administration to the subject, or at least -6 mg / dL over a period of approximately 78 days, wherein the administration is (i) a dose of the drug containing 450 μg of GL0034 once a week for at least two weeks, (ii) a dose of the drug containing 900 μg of GL0034 once a week for at least two weeks, and (iii) a dose of the drug containing 1520 μg of GL0034 once a week for at least four weeks. Embodiment 232: The use according to Embodiment 214, wherein the change in LDL level from baseline is at least -24 mg / dL over a period of approximately 51 days following the administration to the subject, or at least -20 mg / dL over a period of approximately 78 days, wherein the administration is (i) a dose of the drug containing 450 μg of GL0034 once a week for at least two weeks, (ii) a dose of the drug containing 900 μg of GL0034 once a week for at least two weeks, and (iii) a dose of the drug containing 1520 μg of GL0034 once a week for at least four weeks. Embodiment 233: The use according to Embodiment 214, wherein the increase in HDL levels from baseline is at least 3 mg / dL over a period of approximately 78 days following the administration to the subject, the administration being (i) a dose of the drug containing 450 μg of GL0034 once a week for at least two weeks, (ii) a dose of the drug containing 900 μg of GL0034 once a week for at least two weeks, and (iii) a dose of the drug containing 1520 μg of GL0034 once a week for at least four weeks. Embodiment 234: A clinically significant change from baseline in the subjects is a reduction in blood pressure, as described in Embodiment 214 of the use. Embodiment 235: The reduction in blood pressure is a reduction in systolic blood pressure, as described in Embodiment 234. Embodiment 236: The reduction in blood pressure is a reduction in diastolic blood pressure, as described in Embodiment 234. Embodiment 237: The use according to Embodiment 235, wherein the reduction in systolic blood pressure from baseline is at least about 18 mmHg or at least about 14% over a period of about 23 days after administration of a dose of the drug containing 450 μg of GL0034 once a week to the subject for at least 4 weeks. Embodiment 238: The use according to Embodiment 236, wherein the reduction in diastolic blood pressure from baseline is at least about 12 mmHg or at least about 14% over a period of about 23 days after administration of a dose of the drug containing at least 450 μg of GL0034 once a week to the subject for at least 4 weeks. Embodiment 239: The reduction in blood pressure in the subjects is greater than the reduction in blood pressure after administration of (a) 1.7-2.4 mg of semaglutide once a week or (b) 5-15 mg of tilzepatide once a week, as described in Embodiment 234. Embodiment 240: The use according to any one of Embodiments 173 to 239, wherein the administration of the drug to the subject results in a time-dependent decrease in the frequency of adverse events (AEs) in the subject. Embodiment 241: The use according to Embodiment 240, in which the AE is one or more of nausea, vomiting, and / or loss of appetite. Embodiment 242: The reduction in the frequency of AEs is dose-dependent, as described in Embodiment 240. Embodiment 243: The use according to any one of Embodiments 173 to 184, wherein administering a higher dose of the drug to the subject does not result in an increase in severely therapeutic adverse events (TEAEs). Embodiment 244: Use of GL0034 for the manufacture of a drug for treating hypertension in a subject, wherein a therapeutically effective dose of the drug is administered to the subject. Embodiment 245: The subject is obese, as described in Embodiment 244. Embodiment 246: The subject is not diabetes, and the use is as described in Embodiment 245. Embodiment 247: The target population is individuals with metabolic disorders, as described in Embodiment 244. Embodiment 248: The metabolic disorder is metabolic dysfunction-associated fatty liver disease (MASLD), as described in Embodiment 247. Embodiment 249: MASLD is metabolic disorder-associated steatohepatitis (MASH), as described in Embodiment 248. Embodiment 250: The metabolic disorder is diabetes mellitus or hypertriglyceridemia, as described in Embodiment 247. Embodiment 251: The metabolic disorder is type 2 diabetes, as described in Embodiment 250. Embodiment 252: The drug is administered subcutaneously to the subject, as described in any one of Embodiments 244 to 251. Embodiment 253: The drug is administered to the subject by subcutaneous injection, as described in Embodiment 252. Embodiment 254: The drug is administered to the subject using an auto-injector or a pre-filled syringe, as described in Embodiment 253. Embodiment 255: The use described in any one of Embodiments 244 to 254, wherein a dose of the drug containing 450 μg of GL0034 is administered to the subject. Embodiment 256: The use according to Embodiment 255, wherein the administration of the drug results in a reduction of systolic blood pressure from baseline in a subject of at least about 18 mmHg or at least about 14% over a period of about 23 days after the administration of the drug. Embodiment 257: The use according to Embodiment 255, wherein the administration of the drug results in a reduction of diastolic blood pressure from baseline in a subject of at least about 12 mmHg or at least about 14% over a period of about 23 days after the administration of the drug. Embodiment 258: The use according to any one of Embodiments 244 to 257, wherein the reduction in blood pressure in the subject is greater than the reduction in blood pressure after administration of (a) 1.7 to 2.4 mg of semaglutide or (b) 5 to 15 mg. Embodiment 259: A method for treating obesity in a subject, comprising administering a dose of GL0034 of 450 μg, 680 μg, 900 μg, 1520 μg, 2000 μg, or 2520 μg to the subject. Embodiment 260: A method for treating metabolic disorders in a subject, comprising administering a dose of GL0034 of 450 μg, 680 μg, 900 μg, 1520 μg, 2000 μg, or 2520 μg to the subject. Embodiment 261: The method according to Embodiment 260, wherein the metabolic disorder is MASH, MASLD, diabetes mellitus, or hypertriglyceridemia. Embodiment 262: GL0034 is administered subcutaneously to a subject according to the method of either Embodiment 259 or Embodiment 260. Embodiment 263: GL0034 is administered to the subject as a single dose of 1520 μg, 2000 μg, or 2520 μg, according to the method of either Embodiment 259 or Embodiment 260. Embodiment 264: The administration ranged from 226.9±57.3 ng / mL to 367.0±152.0 ng / mL, which is the average maximum concentration (C) of GL0034. max The method according to embodiment 263, which provides ). Embodiment 265: The area under the concentration-time curve (AUC) is such that the administration rate over a 22-day period is between 47,151.5±16,838.6 ng*h / mL and 62,265.9±20,816.5 ng*h / mL. 0-t The method according to embodiment 263, which provides ). Embodiment 266: The administration time is 98.5±13.0 hours to 113.5±22.9 hours, and the plasma drug half-life (t) is 98.5±13.0 hours to 113.5±22.9 hours. 1 / 2 The method according to embodiment 263, which provides ). Embodiment 267: The time to reach peak plasma concentration (T) is 22.0 ± 6.9 hours to 31.0 ± 13.5 hours after administration. max The method according to embodiment 263, which provides ). Embodiment 268: GL0034 is administered to a subject as repeated doses of 450 μg, 680 μg, 900 μg, 1520 μg, 2000 μg, or 2520 μg over a period of up to 8 weeks, according to the method described in either Embodiment 259 or Embodiment 260. Embodiment 269: GL0034 is administered to a subject at a dose of 450 μg once a week for 4 weeks, according to the method described in Embodiment 268. Embodiment 270: The method according to Embodiment 269, wherein the administration provides an average maximum concentration (C max ) of GL0034 that is 100.5 ± 22.0 ng / mL to 141.7 ± 34.6 ng / mL. Embodiment 271: The method according to Embodiment 269, wherein the administration provides an area under the concentration-time curve (AUC 0-t ) that is 12814.2 ± 2652.1 ng*h / mL to 18536.8 ± 4608.2 ng*h / mL over a period of 22 days. Embodiment 272: The method according to Embodiment 269, wherein the administration provides a plasma drug half-life (t 1 / 2 ) that is 102.3 ± 15.4 hours on day 22. Embodiment 273: The method according to Embodiment 269, wherein the administration provides a time to maximum plasma concentration (T max ) that is 36.0 ± 12.0 hours to 47.0 ± 16.0 hours. Embodiment 274: GL0034 is administered to a subject at a dose of 680 μg once a week for 4 weeks, according to the method described in Embodiment 268. <� Embodiment 275: The method according to Embodiment 274, wherein the administration provides an average maximum concentration (C max ) of GL0034 that is 169.0 ± 49.5 ng / mL to 267.0 ± 60.9 ng / mL. Embodiment 276: The method according to Embodiment 274, wherein the administration provides an area under the concentration-time curve (AUC0-t The method according to embodiment 274, which provides ). Embodiment 277: The administration was performed on day 22, when the plasma drug half-life (t) was 122.9 ± 16.5 hours. 1 / 2 The method according to embodiment 274, which provides ). Embodiment 278: The time to reach peak plasma concentration (T) is 39.0±21.0 hours to 54.0±27.0 hours after administration. max The method according to embodiment 274, which provides ). Embodiment 279: The method according to Embodiment 268, wherein GL0034 is administered as follows, the dose being (i) 450 μg once a week for two weeks, (ii) 900 μg once a week for two weeks, and (iii) 1520 μg once a week for four weeks. Embodiment 280: The average maximum concentration (C) of GL0034 administered was 111.7±23.7 ng / mL to 707.6±251.7 ng / mL. max The method according to embodiment 279, which provides ). Embodiment 281: The area under the concentration-time curve (AUC) is such that the administration rate over a 50-day period is between 12942.2±1517.5 ng*h / mL and 76320.4±23334.6 ng*h / mL. 0-t The method according to embodiment 279, which provides ). Embodiment 282: The administration was performed on day 50, with a plasma drug half-life (t) of 106.8 ± 33.7 hours. 1 / 2 The method according to embodiment 279, which provides ). Embodiment 283: The time to reach peak plasma concentration (T) is 22.0 ± 16.0 hours to 41.0 ± 8.0 hours after administration. max The method according to embodiment 279, which provides ). Embodiment 284: The method according to either Embodiment 259 or Embodiment 260, wherein administration of GL0034 to a subject results in one or more clinically significant changes from baseline in the subject, the clinically significant changes from baseline being: weight loss, decrease in glycated hemoglobin (%HbA1c), increase in high-density lipoprotein (HDL) levels, decrease in alanine transaminase (ALT) levels, decrease in aspartate aminotransferase (AST) levels, decrease in gamma-glutamyltransferase (GGT) levels, decrease in triglyceride (TG) levels, decrease in total cholesterol (TC) levels, decrease in low-density lipoprotein (LDL) levels, decrease in TG / HDL ratio, decrease in fasting insulin levels, decrease in fasting blood glucose levels, decrease in homeostasis model assessment of insulin resistance (HOMA-IR), and / or decrease in leptin levels. Embodiment 285: The method according to Embodiment 284, wherein the change in fasting plasma blood glucose level from baseline is at least about -2.8 ± 3.7 mg / dL over a period of about 23 days following the administration of 450 μg of GL0034 once a week for 4 weeks. Embodiment 286: The method according to Embodiment 284, wherein the change in fasting plasma glucose level from baseline is at least about -4.6 ± 2.7 mg / dL over a period of about 23 days following the administration of 680 μg of GL0034 once a week for 4 weeks. Embodiment 287: The change in fasting plasma blood glucose level from baseline is at least about -7.7 ± 9.9 mg / dL over a period of about 51 days after administration of GL0034, wherein the administration is (i) a dose of 450 μg once a week for 2 weeks, (ii) a dose of 900 μg once a week for 2 weeks, and (iii) a dose of 1520 μg once a week for 4 weeks, according to Embodiment 284. Embodiment 288: The method according to Embodiment 284, wherein the change in fasting insulin levels from baseline is at least about -4.6 ± 23.0 pmol / L over a period of about 23 days following the administration of 680 μg of GL0034 once a week for 4 weeks. Embodiment 289: The method according to Embodiment 284, wherein the change in fasting insulin levels from baseline is at least about -11.3 ± 16.5 pmol / L over a period of about 51 days after administration of GL0034, and the administration is (i) a dose of 450 μg once a week for two weeks, (ii) a dose of 900 μg once a week for two weeks, and (iii) a dose of 1520 μg once a week for four weeks. Embodiment 290: The method according to Embodiment 284, wherein the change in ALT level from baseline is at least about -8.8 ± 13.1 U / L over a period of about 23 days following the administration of 450 μg of GL0034 once a week for 4 weeks. Embodiment 291: The method according to Embodiment 284, wherein the change in ALT level from baseline is at least about -3.1 ± 5.8 U / L over a period of about 23 days following the administration of 680 μg of GL0034 once a week for 4 weeks. Embodiment 292: The change in ALT levels from baseline is at least about -7.4 ± 10.3 U / L over a period of about 51 days after administration of GL0034, wherein the administration is (i) a dose of 450 μg once a week for two weeks, (ii) a dose of 900 μg once a week for two weeks, and (iii) a dose of 1520 μg once a week for four weeks, according to Embodiment 284. Embodiment 293: The method according to Embodiment 284, wherein the change in ALT levels from baseline is at least about -1.0 ± 9.4 U / L over a period of about 78 days after administration of GL0034, and the administration is (i) a dose of 450 μg once a week for two weeks, (ii) a dose of 900 μg once a week for two weeks, and (iii) a dose of 1520 μg once a week for four weeks. Embodiment 294: The change in AST levels from baseline is at least about -4.0 ± 7.5 U / L over a period of about 51 days after administration of GL0034, wherein the administration is (i) a dose of 450 μg once a week for two weeks, (ii) a dose of 900 μg once a week for two weeks, and (iii) a dose of 1520 μg once a week for four weeks, according to Embodiment 284. Embodiment 295: The change in AST levels from baseline is at least about -1.1 ± 6.7 U / L over a period of about 78 days after administration of GL0034, wherein the administration is (i) a dose of 450 μg once a week for two weeks, (ii) a dose of 900 μg once a week for two weeks, and (iii) a dose of 1520 μg once a week for four weeks, according to Embodiment 284. Embodiment 296: The method according to Embodiment 284, wherein the change in GGT levels from baseline is at least about -3.4 ± 3.5 U / L over a period of about 51 days after administration of GL0034, and the administration is (i) a dose of 450 μg once a week for two weeks, (ii) a dose of 900 μg once a week for two weeks, and (iii) a dose of 1520 μg once a week for four weeks. Embodiment 297: The method according to Embodiment 284, wherein the change in GGT levels from baseline is at least about -1.0 ± 2.7 U / L over a period of about 78 days after administration of GL0034, and the administration is (i) a dose of 450 μg once a week for two weeks, (ii) a dose of 900 μg once a week for two weeks, and (iii) a dose of 1520 μg once a week for four weeks. Embodiment 298: The method according to Embodiment 284, wherein the change in body weight from baseline is at least about -3.4 ± 1.8 kg over a period of about 29 days following the administration of 450 μg of GL0034 once a week for 4 weeks. Embodiment 299: The method according to Embodiment 284, wherein the change in body weight from baseline is at least about -4.1 ± 1.0 kg over a period of about 29 days following the administration of 680 μg of GL0034 once a week for 4 weeks. Embodiment 300: The method according to Embodiment 284, wherein the change in body weight from baseline is at least about -7.7 ± 1.9 kg over a period of about 52 days after administration of GL0034, and the administration is (i) a dose of 450 μg once a week for two weeks, (ii) a dose of 900 μg once a week for two weeks, and (iii) a dose of 1520 μg once a week for four weeks. Embodiment 301: The method according to Embodiment 284, wherein the change in body weight from baseline is at least about -6.4 ± 2.1 kg over a period of about 78 days after administration of GL0034, and the administration is (i) a dose of 450 μg once a week for two weeks, (ii) a dose of 900 μg once a week for two weeks, and (iii) a dose of 1520 μg once a week for four weeks. Embodiment 302: The change in %HbA1c from baseline is at least about -0.25 ± 0.2 over a period of about 78 days after administration of GL0034, wherein the administration is (i) a dose of 450 μg once a week for two weeks, (ii) a dose of 900 μg once a week for two weeks, and (iii) a dose of 1520 μg once a week for four weeks, according to Embodiment 284. Embodiment 303: The change in TG levels from baseline is at least about -21.0 ± 27.5 mg / dL over a period of about 51 days after administration of GL0034, wherein the administration is (i) a dose of 450 μg once a week for two weeks, (ii) a dose of 900 μg once a week for two weeks, and (iii) a dose of 1520 μg once a week for four weeks, according to Embodiment 284. Embodiment 304: The change in TG level from baseline is at least about -11.0 ± 55.3 mg / dL over a period of about 78 days after administration of GL0034 as follows, and the administration is (i) a dose of 450 μg once a week for 2 weeks, (ii) a dose of 900 μg once a week for 2 weeks, and (iii) a dose of 1520 μg once a week for 4 weeks, the method according to Embodiment 284. Embodiment 305: The change in TC level from baseline is at least about -29.1 ± 23.3 mg / dL over a period of about 51 days after administration of GL0034 as follows, and the administration is (i) a dose of 450 μg once a week for 2 weeks, (ii) a dose of 900 μg once a week for 2 weeks, and (iii) a dose of 1520 μg once a week for 4 weeks, the method according to Embodiment 284. Embodiment 306: The change in TC level from baseline is at least about -5.8 ± 12.6 mg / dL over a period of about 78 days after administration of GL0034 as follows, and the administration is (i) a dose of 450 μg once a week for 2 weeks, (ii) a dose of 900 μg once a week for 2 weeks, and (iii) a dose of 1520 μg once a week for 4 weeks, the method according to Embodiment 284. Embodiment 307: The change in LDL level from baseline is at least about -24.0 ± 24.3 mg / dL over a period of about 51 days after administration of GL0034 as follows, and the administration is (i) a dose of 450 μg once a week for 2 weeks, (ii) a dose of 900 μg once a week for 2 weeks, and (iii) a dose of 1520 μg once a week for 4 weeks, the method according to Embodiment 284. Embodiment 308: The change in LDL levels from baseline is at least about -19.5 ± 35.8 mg / dL over a period of about 78 days after administration of GL0034, wherein the administration is (i) a dose of 450 μg once a week for two weeks, (ii) a dose of 900 μg once a week for two weeks, and (iii) a dose of 1520 μg once a week for four weeks, according to Embodiment 284. Embodiment 309: The method according to Embodiment 846, wherein the change in HDL levels from baseline is at least about 2.9 ± 3.1 mg / dL over a period of about 78 days after administration of GL0034, and the administration is (i) a dose of 450 μg once a week for two weeks, (ii) a dose of 900 μg once a week for two weeks, and (iii) a dose of 1520 μg once a week for four weeks. Embodiment 310: The method according to Embodiment 284, wherein the change in body weight from baseline is at least about -2.4 ± 2.2 kg over a period of about 22 days following administration of GL0034 as a single dose of 1520 μg. Embodiment 311: The method according to Embodiment 284, wherein the change in body weight from baseline is at least about -1.8 ± 2.4 kg over a period of about 22 days following administration of GL0034 as a single dose of 2000 μg. Embodiment 312: The method according to Embodiment 284, wherein the change in body weight from baseline is at least about -3.1 ± 1.7 kg over a period of about 22 days following administration of GL0034 as a single dose of 2520 μg. Embodiment 313: The method according to Embodiment 284, wherein the change in TG levels from baseline is at least about -0.4 ± 0.4 mmol / L over a period of about 8 days following administration of GL0034 as a single dose of 1520 μg. Embodiment 314: The method according to Embodiment 284, wherein the change in TG levels from baseline is at least about -0.8 ± 0.5 mmol / L over a period of about 8 days following administration of GL0034 as a single dose of 2000 μg. Embodiment 315: The method according to Embodiment 284, wherein the change in TG levels from baseline is at least about -0.5 ± 0.5 mmol / L over a period of about 22 days following administration of GL0034 as a single dose of 2520 μg. Embodiment 316: The method according to Embodiment 284, wherein the change in leptin levels from baseline is at least about -6.9 ± 5.1 ng / mL over a period of about 8 days following administration of GL0034 as a single dose of 1520 μg. Embodiment 317: The method according to Embodiment 284, wherein the change in leptin levels from baseline is at least about -10.9 ± 8.6 ng / mL over a period of about 8 days following administration of GL0034 as a single dose of 2000 μg. Embodiment 318: The method according to Embodiment 284, wherein the change in leptin levels from baseline is at least about -11.6 ± 12.8 ng / mL over a period of about 8 days following administration of GL0034 as a single dose of 2520 μg. Embodiment 319: The method according to either Embodiment 259 or Embodiment 260, comprising administering an initial dose for at least approximately two weeks, administering an escalating dose once a week for at least approximately two weeks, and administering a maintenance dose once a week for at least approximately four weeks, wherein the initial dose is approximately 450 μg or approximately 680 μg, the escalating dose is approximately 680 μg or approximately 900 μg, and the maintenance dose is approximately 1520 μg or approximately 2000 μg. Embodiment 320: The method according to either Embodiment 259 or Embodiment 260, comprising administering an initial dose for at least about four weeks and administering gradually increasing doses once a week for at least about two weeks, wherein the initial dose is about 450 μg or about 680 μg, and the gradually increasing doses are about 680 μg or about 900 μg. Embodiment 321: The method according to either Embodiment 259 or Embodiment 260, comprising administering an initial dose for at least approximately 4 weeks, administering an escalating dose once a week for at least approximately 2 weeks, and administering a maintenance dose once a week for at least approximately 2 weeks, wherein the initial dose is approximately 450 μg or approximately 680 μg, the escalating dose is approximately 680 μg or approximately 900 μg, and the maintenance dose is approximately 1520 μg or approximately 2000 μg. Embodiment 322: A pharmaceutical composition of GL0034 for the treatment of obesity in a subject, wherein the dosage of the pharmaceutical composition is 450 μg, 680 μg, 900 μg, 1520 μg, 2000 μg, or 2520 μg of GL0034. Embodiment 323: A pharmaceutical composition of GL0034 for the treatment of metabolic disorders in a subject, wherein the dosage of the pharmaceutical composition is 450 μg, 680 μg, 900 μg, 1520 μg, 2000 μg, or 2520 μg of GL0034. Embodiment 324: The pharmaceutical composition according to Embodiment 323, wherein the metabolic disorder is MASH, MASLD, diabetes mellitus, or hypertriglyceridemia. Embodiment 325: The pharmaceutical composition is administered subcutaneously to a subject, as described in either embodiment 322 or 323. Embodiment 326: The pharmaceutical composition according to either Embodiment 322 or Embodiment 323, wherein the dosage of the pharmaceutical composition comprises 1520 μg, 2000 μg, or 2520 μg of GL0034, and a single dose of the pharmaceutical composition is administered to the subject. Embodiment 327: The administration of the pharmaceutical composition results in an average maximum concentration (C max ) of GL0034 that is 226.9 ± 57.3 ng / mL to 367.0 ± 152.0 ng / mL, the pharmaceutical composition according to embodiment 326. Embodiment 328: The administration of the pharmaceutical composition results in an area under the concentration-time curve (AUC 0-t ) that is 47,151.5 ± 16,838.6 ng*h / mL to 62,265.9 ± 20,816.5 ng*h / mL over a 22-day period, the pharmaceutical composition according to embodiment 326. Embodiment 329: The administration of the pharmaceutical composition results in a plasma drug half-life (t 1 / 2 ) that is 98.5 ± 13.0 hours to 113.5 ± 22.9 hours, the pharmaceutical composition according to embodiment 326. Embodiment 330: The administration of the pharmaceutical composition results in a time to maximum plasma concentration (T max ) that is 22.0 ± 6.9 hours to 31.0 ± 13.5 hours, the pharmaceutical composition according to embodiment 326. Embodiment 331: The dosage of the pharmaceutical composition includes 450 μg, 680 μg, 900 μg, 1520 μg, 2000 μg, or 2520 μg of GL0034, and the repeated administration of the pharmaceutical composition is administered to the subject over a period of up to 8 weeks, the pharmaceutical composition according to either embodiment 322 or embodiment 323. Embodiment 332: GL0034 is administered to the subject at a dosage of 450 μg once a week for 4 weeks, the pharmaceutical composition according to embodiment 331. Embodiment 333: The administration of the pharmaceutical composition results in an average maximum concentration (C max ) of GL0034 that is 100.5 ± 22.0 ng / mL to 141.7 ± 34.6 ng / mL, the pharmaceutical composition according to embodiment 332. Embodiment 334: The administration of the pharmaceutical composition results in an area under the concentration-time curve (AUC 0-t ) that is 12814.2 ± 2652.1 ng*h / mL to 18536.8 ± 4608.2 ng*h / mL over a 22-day period,The pharmaceutical composition according to Embodiment 332, which results in Embodiment 335: The administration of the pharmaceutical composition results in a plasma drug half-life (t 1 / 2 ) of 102.3 ± 15.4 hours on the 22nd day, the pharmaceutical composition according to Embodiment 332. Embodiment 336: The administration of the pharmaceutical composition results in a time to reach maximum plasma concentration (T max ) of 36.0 ± 12.0 hours to 47.0 ± 16.0 hours, the pharmaceutical composition according to Embodiment 332. Embodiment 337: The dose of the pharmaceutical composition includes 680 μg, and the pharmaceutical composition is administered to the subject once a week for 4 weeks, the pharmaceutical composition according to Embodiment 331. Embodiment 338: The administration of the pharmaceutical composition results in an average maximum concentration (C max ) of GL0034 of 169.0 ± 49.5 ng / mL to 267.0 ± 60.9 ng / mL, the pharmaceutical composition according to Embodiment 337. Embodiment 339: The administration of the pharmaceutical composition results in an area under the concentration-time curve (AUC 0-t ) of 24575.9 ± 3391.2 ng*h / mL to 34536.6 ± 6445.0 ng*h / mL over a 22-day period, the pharmaceutical composition according to Embodiment 337. Embodiment 340: The administration of the pharmaceutical composition results in a plasma drug half-life (t 1 / 2 ) of 122.9 ± 16.5 hours on the 22nd day, the pharmaceutical composition according to Embodiment 337. Embodiment 341: The administration of the pharmaceutical composition results in a time to reach maximum plasma concentration (T max ) of 39.0 ± 21.0 hours to 54.0 ± 27.0 hours, the pharmaceutical composition according to Embodiment 337. Embodiment 342: The pharmaceutical composition according to Embodiment 331, wherein (i) a first dose of the pharmaceutical composition comprises 450 μg of GL0034, and the first dose of the pharmaceutical composition is administered to the subject once a week for two weeks; (ii) a second dose of the pharmaceutical composition comprises 900 μg of GL0034, and the second dose of the pharmaceutical composition is administered to the subject once a week for two weeks; and (iii) a third dose of the pharmaceutical composition comprises 1520 μg of GL0034, and the third dose of the pharmaceutical composition is administered to the subject once a week for four weeks. Embodiment 343: The average maximum concentration (C) of GL0034, where the administration of the pharmaceutical composition is 111.7±23.7 ng / mL to 707.6±251.7 ng / mL. max The pharmaceutical composition according to embodiment 342, which brings about ). Embodiment 344: The area under the concentration-time curve (AUC) of a pharmaceutical composition administered at a concentration of 12942.2±1517.5 ng*h / mL to 76320.4±23334.6 ng*h / mL over a 50-day period. 0-t The pharmaceutical composition according to embodiment 342, which brings about ). Embodiment 345: The administration of the pharmaceutical composition results in a plasma drug half-life (t) of 106.8 ± 33.7 hours on day 50. 1 / 2 The pharmaceutical composition according to embodiment 342, which brings about ). Embodiment 346: The time to reach peak plasma concentration (T) is 22.0 ± 16.0 hours to 41.0 ± 8.0 hours after administration of the pharmaceutical composition. max The pharmaceutical composition according to embodiment 342, which brings about ). Embodiment 347: The pharmaceutical composition according to either Embodiment 322 or Embodiment 323, wherein administration of the pharmaceutical composition results in one or more clinically significant changes from baseline in the subject, the clinically significant changes from baseline being: a decrease in body weight, a decrease in glycated hemoglobin (%HbA1c), an increase in high-density lipoprotein (HDL) levels, a decrease in alanine transaminase (ALT) levels, a decrease in aspartate aminotransferase (AST) levels, a decrease in gamma-glutamyltransferase (GGT) levels, a decrease in triglyceride (TG) levels, a decrease in total cholesterol (TC) levels, a decrease in low-density lipoprotein (LDL) levels, a decrease in the TG / HDL ratio, a decrease in fasting insulin levels, a decrease in fasting blood glucose levels, a decrease in the homeostasis model assessment of insulin resistance (HOMA-IR), and / or a decrease in leptin levels. Embodiment 348: The pharmaceutical composition according to Embodiment 347, wherein the change in fasting plasma blood glucose level from baseline is at least about -2.8 ± 3.7 mg / dL over a period of about 23 days after administration of a dose of the pharmaceutical composition containing 450 μg of GL0034, and the pharmaceutical composition is administered to the subject once a week for a period of 4 weeks. Embodiment 349: The pharmaceutical composition according to Embodiment 347, wherein the change in fasting plasma blood glucose level from baseline is at least about -4.6 ± 2.7 mg / dL over a period of about 23 days after administration of a dose of the pharmaceutical composition containing 680 μg of GL0034, and the pharmaceutical composition is administered to the subject once a week for a period of 4 weeks. Embodiment 350: The change in fasting plasma blood glucose level from baseline is at least about -7.7 ± 9.9 mg / dL over a period of about 51 days after administration, wherein the administration is (i) a dose of the pharmaceutical composition containing 450 μg of GL0034, administered once a week for two weeks; (ii) a dose of the pharmaceutical composition containing 900 μg of GL0034, administered once a week for two weeks; and (iii) a dose of the pharmaceutical composition containing 1520 μg, administered once a week for four weeks, according to Embodiment 347. Embodiment 351: The pharmaceutical composition according to Embodiment 347, wherein the change in fasting insulin level from baseline is at least about -4.6 ± 23.0 pmol / L over a period of about 23 days after administration of a dose of the pharmaceutical composition containing 680 μg of GL0034, and the pharmaceutical composition is administered to the subject once a week for a period of 4 weeks. Embodiment 352: The change in fasting insulin levels from baseline is at least about -11.3 ± 16.5 pmol / L over a period of about 51 days after the following administrations, wherein the administrations are (i) a dose of the pharmaceutical composition containing 450 μg of GL0034, administered to the subject once a week for two weeks; (ii) a dose of the pharmaceutical composition containing 900 μg of GL0034, administered to the subject once a week for two weeks; and (iii) a dose of the pharmaceutical composition containing 1520 μg of GL0034, administered to the subject once a week for four weeks, according to Embodiment 347. Embodiment 353: The change in ALT levels from baseline is at least about -8.8 ± 13.1 U / L over a period of about 23 days after administration of a dose of the pharmaceutical composition containing 450 μg of GL0034, and the pharmaceutical composition is administered to the subject once a week for four weeks, as described in Embodiment 347. Embodiment 354: The change in ALT levels from baseline is at least about -3.1 ± 5.8 U / L over a period of about 23 days after administration of a dose of the pharmaceutical composition containing 680 μg of GL0034, and the pharmaceutical composition is administered to the subject once a week for four weeks, as described in Embodiment 347. Embodiment 355: The change in ALT levels from baseline is at least about -7.4 ± 10.3 U / L over a period of about 51 days after the following administrations, wherein the administrations are (i) a dose of the pharmaceutical composition containing 450 μg of GL0034, administered to the subject once a week for two weeks; (ii) a dose of the pharmaceutical composition containing 900 μg of GL0034, administered to the subject once a week for two weeks; and (iii) a dose of the pharmaceutical composition containing 1520 μg of GL0034, administered to the subject once a week for four weeks, as described in Embodiment 347. Embodiment 356: The change in ALT levels from baseline is at least about -1.0 ± 9.4 U / L over a period of about 78 days after the following administrations, wherein the administrations are (i) a dose of the pharmaceutical composition containing 450 μg of GL0034, administered to the subject once a week for two weeks; (ii) a dose of the pharmaceutical composition containing 900 μg of GL0034, administered to the subject once a week for two weeks; and (iii) a dose of the pharmaceutical composition containing 1520 μg of GL0034, administered to the subject once a week for four weeks, according to Embodiment 347. Embodiment 357: The change in AST levels from baseline is at least about -4.0 ± 7.5 U / L over a period of about 51 days after the following administrations, wherein the administrations are (i) a dose of the pharmaceutical composition containing 450 μg of GL0034, administered to the subject once a week for two weeks; (ii) a dose of the pharmaceutical composition containing 900 μg of GL0034, administered to the subject once a week for two weeks; and (iii) a dose of the pharmaceutical composition containing 1520 μg of GL0034, administered to the subject once a week for four weeks, as described in Embodiment 347. Embodiment 358: The change in AST levels from baseline is at least about -1.1 ± 6.7 U / L over a period of about 78 days after the following administrations, wherein the administrations are (i) a dose of the pharmaceutical composition containing 450 μg of GL0034, administered to the subject once a week for two weeks; (ii) a dose of the pharmaceutical composition containing 900 μg of GL0034, administered to the subject once a week for two weeks; and (iii) a dose of the pharmaceutical composition containing 1520 μg of GL0034, administered to the subject once a week for four weeks, according to Embodiment 347. Embodiment 359: The change in GGT levels from baseline is at least about -3.4 ± 3.5 U / L over a period of about 51 days after the following administrations, wherein the administrations are (i) a dose of the pharmaceutical composition containing 450 μg of GL0034, administered to the subject once a week for two weeks; (ii) a dose of the pharmaceutical composition containing 900 μg of GL0034, administered to the subject once a week for two weeks; and (iii) a dose of the pharmaceutical composition containing 1520 μg of GL0034, administered to the subject once a week for four weeks, as described in Embodiment 347. Embodiment 360: The change in GGT levels from baseline is at least about -1.0 ± 2.7 U / L over a period of about 78 days after the following administrations, wherein the administrations are (i) a dose of the pharmaceutical composition containing 450 μg of GL0034, administered to the subject once a week for two weeks; (ii) a dose of the pharmaceutical composition containing 900 μg of GL0034, administered to the subject once a week for two weeks; and (iii) a dose of the pharmaceutical composition containing 1520 μg of GL0034, administered to the subject once a week for four weeks, according to Embodiment 347. Embodiment 361: The change in body weight from baseline is at least about -3.4 ± 1.8 kg over a period of about 29 days after administration of a dose of the pharmaceutical composition containing 450 μg of GL0034, and the pharmaceutical composition is administered to the subject once a week for four weeks, as described in Embodiment 347. Embodiment 362: The change in body weight from baseline is at least about -4.1 ± 1.0 kg over a period of about 29 days after administration of a dose of the pharmaceutical composition containing 680 μg of GL0034, and the pharmaceutical composition is administered to the subject once a week for four weeks, as described in Embodiment 347. Embodiment 363: The change in body weight from baseline is at least about -7.7 ± 1.9 kg over a period of about 52 days after the following administrations, wherein the administrations are (i) a dose of the pharmaceutical composition containing 450 μg of GL0034, administered to the subject once a week for two weeks; (ii) a dose of the pharmaceutical composition containing 900 μg of GL0034, administered to the subject once a week for two weeks; and (iii) a dose of the pharmaceutical composition containing 1520 μg of GL0034, administered to the subject once a week for four weeks, as described in Embodiment 347. Embodiment 364: The change in body weight from baseline is at least about -6.4 ± 2.1 kg over a period of about 78 days after the following administrations, wherein the administrations are (i) a dose of the pharmaceutical composition containing 450 μg of GL0034, administered to the subject once a week for two weeks; (ii) a dose of the pharmaceutical composition containing 900 μg of GL0034, administered to the subject once a week for two weeks; and (iii) a dose of the pharmaceutical composition containing 1520 μg of GL0034, administered to the subject once a week for four weeks, as described in Embodiment 347. Embodiment 365: The change in %HbA1c from baseline is at least about -0.25 ± 0.2 over a period of about 78 days after the following administrations, wherein the administrations are (i) a dose of the pharmaceutical composition containing 450 μg of GL0034, administered to the subject once a week for two weeks; (ii) a dose of the pharmaceutical composition containing 900 μg of GL0034, administered to the subject once a week for two weeks; and (iii) a dose of the pharmaceutical composition containing 1520 μg of GL0034, administered to the subject once a week for four weeks, as described in Embodiment 347. Embodiment 366: The change in TG levels from baseline is at least about -21.0 ± 27.5 mg / dL over a period of about 51 days after the following administrations, wherein the administrations are (i) a dose of the pharmaceutical composition containing 450 μg of GL0034, administered to the subject once a week for two weeks; (ii) a dose of the pharmaceutical composition containing 900 μg of GL0034, administered to the subject once a week for two weeks; and (iii) a dose of the pharmaceutical composition containing 1520 μg of GL0034, administered to the subject once a week for four weeks, as described in Embodiment 347. Embodiment 367: The change in TG levels from baseline is at least about -11.0 ± 55.3 mg / dL over a period of about 78 days after the following administrations, wherein the administrations are (i) a dose of the pharmaceutical composition containing 450 μg of GL0034, administered to the subject once a week for two weeks; (ii) a dose of the pharmaceutical composition containing 900 μg of GL0034, administered to the subject once a week for two weeks; and (iii) a dose of the pharmaceutical composition containing 1520 μg of GL0034, administered to the subject once a week for four weeks, as described in Embodiment 347. Embodiment 368: The change in TC level from baseline is at least about -29.1 ± 23.3 mg / dL over a period of about 51 days after the following administrations, wherein the administrations are (i) a dose of the pharmaceutical composition containing 450 μg of GL0034, administered to the subject once a week for two weeks; (ii) a dose of the pharmaceutical composition containing 900 μg of GL0034, administered to the subject once a week for two weeks; and (iii) a dose of the pharmaceutical composition containing 1520 μg of GL0034, administered to the subject once a week for four weeks, according to Embodiment 347. Embodiment 369: The change in TC level from baseline is at least about -5.8 ± 12.6 mg / dL over a period of about 78 days after the following administrations, wherein the administrations are (i) a dose of the pharmaceutical composition containing 450 μg of GL0034, administered to the subject once a week for two weeks; (ii) a dose of the pharmaceutical composition containing 900 μg of GL0034, administered to the subject once a week for two weeks; and (iii) a dose of the pharmaceutical composition containing 1520 μg of GL0034, administered to the subject once a week for four weeks, according to Embodiment 347. Embodiment 370: The change in LDL level from baseline is at least about -24.0 ± 24.3 mg / dL over a period of about 51 days after administration, wherein the administration is (i) a dose of the pharmaceutical composition containing 450 μg of GL0034, administered to the subject once a week for two weeks; (ii) a dose of the pharmaceutical composition containing 900 μg of GL0034, administered to the subject once a week for two weeks; and (iii) a dose of the pharmaceutical composition containing 1520 μg of GL0034, administered to the subject once a week for four weeks, according to Embodiment 347. Embodiment 371: The change in LDL level from baseline is at least about -19.5 ± 35.8 mg / dL over a period of about 78 days after administration, wherein the administration is (i) a dose of the pharmaceutical composition containing 450 μg of GL0034, administered to the subject once a week for two weeks; (ii) a dose of the pharmaceutical composition containing 900 μg of GL0034, administered to the subject once a week for two weeks; and (iii) a dose of the pharmaceutical composition containing 1520 μg of GL0034, administered to the subject once a week for four weeks, according to Embodiment 347. Embodiment 372: The change in HDL levels from baseline is at least about 2.9 ± 3.1 mg / dL over a period of about 78 days after administration, wherein the administration is (i) a dose of the pharmaceutical composition containing 450 μg of GL0034, administered to the subject once a week for two weeks; (ii) a dose of the pharmaceutical composition containing 900 μg of GL0034, administered to the subject once a week for two weeks; and (iii) a dose of the pharmaceutical composition containing 1520 μg of GL0034, administered to the subject once a week for four weeks, according to Embodiment 347. Embodiment 373: The pharmaceutical composition according to Embodiment 347, wherein the change in body weight from baseline is at least about -2.4 ± 2.2 kg over a period of about 22 days following administration of a single dose of the pharmaceutical composition containing 1520 μg of GL0034. Embodiment 374: The pharmaceutical composition according to Embodiment 347, wherein the change in body weight from baseline is at least about -1.8 ± 2.4 kg over a period of about 22 days following administration of a single dose of the pharmaceutical composition containing 2000 μg of GL0034. Embodiment 375: The pharmaceutical composition according to Embodiment 347, wherein the change in body weight from baseline is at least about -3.1 ± 1.7 kg over a period of about 22 days following administration of a single dose of the pharmaceutical composition containing 2520 μg of GL0034. Embodiment 376: The pharmaceutical composition according to Embodiment 347, wherein the change in TG levels from baseline is at least about -0.4 ± 0.4 mmol / L over a period of about 8 days following administration of a single dose of the pharmaceutical composition containing 1520 μg of GL0034. Embodiment 377: The pharmaceutical composition according to Embodiment 347, wherein the change in TG levels from baseline is at least about -0.8 ± 0.5 mmol / L over a period of about 8 days following administration of a single dose of the pharmaceutical composition containing 2000 μg of GL0034. Embodiment 378: The pharmaceutical composition according to Embodiment 347, wherein the change in TG levels from baseline is at least about -0.5 ± 0.5 mmol / L over a period of about 22 days following administration of a single dose of the pharmaceutical composition containing 2520 μg of GL0034. Embodiment 379: The pharmaceutical composition according to Embodiment 347, wherein the change in leptin level from baseline is at least about -6.9 ± 5.1 ng / mL over a period of about 8 days following administration of a single dose of the pharmaceutical composition containing 1520 μg of GL0034. Embodiment 380: The pharmaceutical composition according to Embodiment 347, wherein the change in leptin level from baseline is at least about -10.9 ± 8.6 ng / mL over a period of about 8 days following administration of a single dose of the pharmaceutical composition containing 2000 μg of GL0034. Embodiment 381: The pharmaceutical composition according to Embodiment 347, wherein the change in leptin levels from baseline is at least about -11.6 ± 12.8 ng / mL over a period of about 8 days following administration of a single dose of the pharmaceutical composition containing 2520 μg of GL0034. Embodiment 382: A pharmaceutical composition according to either Embodiment 322 or Embodiment 323, wherein the initial dose of the pharmaceutical composition containing approximately 450 μg or approximately 680 μg of GL0034 is administered to the subject for at least approximately two weeks, the escalating dose of the pharmaceutical composition containing approximately 680 μg or approximately 900 μg of GL0034 is administered to the subject once a week for at least approximately two weeks, and the maintenance dose of the pharmaceutical composition containing approximately 1520 μg or approximately 2000 μg of GL0034 is administered to the subject once a week for at least approximately four weeks. Embodiment 383: A pharmaceutical composition according to either Embodiment 322 or Embodiment 323, wherein an initial dose of a pharmaceutical composition containing approximately 450 μg or approximately 680 μg of GL0034 is administered to the subject for at least approximately 4 weeks, and gradually increasing doses of a pharmaceutical composition containing approximately 680 μg or approximately 900 μg of GL0034 are administered to the subject once a week for at least approximately 2 weeks. Embodiment 384: A pharmaceutical composition according to either Embodiment 322 or Embodiment 323, wherein an initial dose of a pharmaceutical composition containing approximately 450 μg or approximately 680 μg of GL0034 is administered to the subject for at least approximately 4 weeks, an increasing dose of a pharmaceutical composition containing approximately 680 μg or approximately 900 μg of GL0034 is administered to the subject once a week for at least approximately 2 weeks, and a maintenance dose of a pharmaceutical composition containing approximately 1520 μg or approximately 2000 μg of GL0034 is administered to the subject once a week for at least approximately 2 weeks. Embodiment 385: Use of GL0034 for the manufacture of a drug for treating obesity in a subject, wherein the drug dose comprises 450 μg, 680 μg, 900 μg, 1520 μg, 2000 μg, or 2520 μg of GL0034. Embodiment 386: Use of GL0034 for the manufacture of a drug for treating metabolic disorders in a subject, wherein the drug dose comprises 450 μg, 680 μg, 900 μg, 1520 μg, 2000 μg, or 2520 μg of GL0034. Embodiment 387: The metabolic disorder is MASH, MASLD, diabetes mellitus, or hypertriglyceridemia, as described in Embodiment 386. Embodiment 388: The drug is administered subcutaneously to the subject, as described in either Embodiment 385 or Embodiment 386. Embodiment 389: The drug dose comprises 1520 μg, 2000 μg, or 2520 μg of GL0034, and the drug is administered as a single dose to the subject, as described in either Embodiment 385 or Embodiment 386. Embodiment 390: The average maximum concentration (C) of GL0034 was 226.9±57.3 ng / mL to 367.0±152.0 ng / mL when the drug was administered. max The use described in Embodiment 389 brings about the following: Embodiment 391: The area under the concentration-time curve (AUC) for drug administration over a 22-day period, where the concentration is between 47,151.5±16,838.6 ng*h / mL and 62,265.9±20,816.5 ng*h / mL. 0-t The use described in Embodiment 389 brings about the following: Embodiment 392: The administration of the drug is considered to have a plasma drug half-life (t) of 98.5 ± 13.0 hours to 113.5 ± 22.9 hours. 1 / 2 The use described in Embodiment 389 brings about the following: Embodiment 393: The time to reach peak plasma concentration (T) is 22.0 ± 6.9 hours to 31.0 ± 13.5 hours after drug administration.max The use described in Embodiment 389 brings about the following: Embodiment 394: The drug dose comprises GL0034 in amounts of 450 μg, 680 μg, 900 μg, 1520 μg, 2000 μg, or 2520 μg, and repeated administration of the drug is performed on the subject over a period of up to 8 weeks, as described in either Embodiment 385 or Embodiment 386. Embodiment 395: The use of GL0034 according to Embodiment 394, wherein GL0034 is administered to the subject once a week for four weeks at a dose of 450 μg. Embodiment 396: The average maximum concentration (C) of GL0034 administered was 100.5±22.0 ng / mL to 141.7±34.6 ng / mL. max The use described in Embodiment 395 brings about the following: Embodiment 397: The area under the concentration-time curve (AUC) for drug administration over a 22-day period, where the concentration is between 12814.2±2652.1 ng*h / mL and 18536.8±4608.2 ng*h / mL. 0-t The use described in Embodiment 395 brings about the following: Embodiment 398: The drug was administered on day 22, with a plasma drug half-life (t) of 102.3 ± 15.4 hours. 1 / 2 The use described in Embodiment 395 brings about the following: Embodiment 399: The time to reach peak plasma concentration (T) is 36.0 ± 12.0 hours to 47.0 ± 16.0 hours after drug administration. max The use described in Embodiment 395 brings about the following: Embodiment 400: The use according to Embodiment 394, wherein the drug dose contains 680 μg, and the drug is administered to the subject once a week for a period of four weeks. Embodiment 401: The average maximum concentration (C) of GL0034 administered was 169.0±49.5 ng / mL to 267.0±60.9 ng / mL. max The use described in Embodiment 400 brings about the following: Embodiment 402: The area under the concentration-time curve (AUC) for drug administration over a 22-day period, where the concentration is between 24575.9±3391.2 ng*h / mL and 34536.6±6445.0 ng*h / mL. 0-t The use described in Embodiment 400 brings about the following: Embodiment 403: The drug was administered on day 22, with a plasma drug half-life (t) of 122.9 ± 16.5 hours. 1 / 2 The use described in Embodiment 400 brings about the following: Embodiment 404: The time to reach peak plasma concentration (T) is 39.0 ± 21.0 hours to 54.0 ± 27.0 hours after drug administration. max The use described in Embodiment 400 brings about the following: Embodiment 405: The use according to Embodiment 394, wherein (i) the first dose of the drug contains 450 μg of GL0034, and the first dose of the drug is administered to the subject once a week for two weeks; (ii) the second dose of the drug contains 900 μg of GL0034, and the second dose of the drug is administered to the subject once a week for two weeks; and (iii) the third dose of the drug contains 1520 μg of GL0034, and the third dose of the drug is administered to the subject once a week for four weeks. Embodiment 406: The average maximum concentration (C) of GL0034 administered was 111.7±23.7 ng / mL to 707.6±251.7 ng / mL. max The use described in Embodiment 405 brings about the following: Embodiment 407: The area under the concentration-time curve (AUC) for drug administration over a 50-day period is 12942.2±1517.5 ng*h / mL to 76320.4±23334.6 ng*h / mL. 0-t The use described in Embodiment 405 brings about the following: Embodiment 408: The drug administration was performed on day 50, with a plasma drug half-life (t) of 106.8 ± 33.7 hours. 1 / 2 The use described in Embodiment 405 brings about the following: Embodiment 409: The time to reach peak plasma concentration (T) is 22.0 ± 16.0 hours to 41.0 ± 8.0 hours after drug administration. max The use described in Embodiment 327 brings about the following: Embodiment 410: The use according to either Embodiment 385 or Embodiment 386, wherein the administration of the drug results in one or more clinically significant changes from baseline in the subject, the clinically significant changes from baseline being: weight loss, decrease in glycated hemoglobin (%HbA1c), increase in high-density lipoprotein (HDL) levels, decrease in alanine transaminase (ALT) levels, decrease in aspartate aminotransferase (AST) levels, decrease in gamma-glutamyltransferase (GGT) levels, decrease in triglyceride (TG) levels, decrease in total cholesterol (TC) levels, decrease in low-density lipoprotein (LDL) levels, decrease in TG / HDL ratio, decrease in fasting insulin levels, decrease in fasting blood glucose levels, decrease in homeostasis model assessment of insulin resistance (HOMA-IR), and / or decrease in leptin levels. Embodiment 411: The change in fasting plasma blood glucose level from baseline is at least about -2.8 ± 3.7 mg / dL over a period of about 23 days after administration of a dose of the drug containing 450 μg of GL0034, and the drug is administered to the subject once a week for a period of 4 weeks, as described in Embodiment 410. Embodiment 412: The change in fasting plasma blood glucose level from baseline was at least about -4.6 ± 2.7 mg / dL over a period of about 23 days after administration of a dose of the drug containing 680 μg of GL0034, and the drug is administered to the subject once a week for a period of 4 weeks, as described in Embodiment 410. Embodiment 413: The change in fasting plasma blood glucose level from baseline is at least about -7.7 ± 9.9 mg / dL over a period of about 51 days after administration, wherein the administration is (i) a dose of the drug containing 450 μg of GL0034, administered once a week for two weeks; (ii) a dose of the drug containing 900 μg of GL0034, administered once a week for two weeks; and (iii) a dose of the drug containing 1520 μg, administered once a week for four weeks, as described in Embodiment 410. Embodiment 414: The change in fasting insulin levels from baseline is at least about -4.6 ± 23.0 pmol / L over a period of about 23 days after administration of a dose of the drug containing 680 μg of GL0034, as described in Embodiment 410, where the drug is administered to the subject once a week for a period of 4 weeks. Embodiment 415: The change in fasting insulin levels from baseline is at least about -11.3 ± 16.5 pmol / L over a period of about 51 days after the following administrations, wherein the administrations are (i) a dose of the drug containing 450 μg of GL0034 administered to the subject once a week for two weeks, (ii) a dose of the drug containing 900 μg of GL0034 administered to the subject once a week for two weeks, and (iii) a dose of the drug containing 1520 μg of GL0034 administered to the subject once a week for four weeks, as described in Embodiment 410. Embodiment 416: The change in ALT levels from baseline was at least about -8.8 ± 13.1 U / L over a period of about 23 days after administration of a dose of the drug containing 450 μg of GL0034, as described in Embodiment 410, where the drug is administered to the subject once a week for a period of 4 weeks. Embodiment 417: The change in ALT levels from baseline was at least about -3.1 ± 5.8 U / L over a period of about 23 days after administration of a dose of the drug containing 680 μg of GL0034, as described in Embodiment 410, where the drug is administered to the subject once a week for a period of 4 weeks. Embodiment 418: The change in ALT levels from baseline is at least about -7.4 ± 10.3 U / L over a period of about 51 days after the following administrations, wherein the administrations are (i) doses of the drug containing 450 μg of GL0034 administered to the subject once a week for two weeks, (ii) doses of the drug containing 900 μg of GL0034 administered to the subject once a week for two weeks, and (iii) doses of the drug containing 1520 μg of GL0034 administered to the subject once a week for four weeks, as described in Embodiment 410. Embodiment 419: The change in ALT levels from baseline is at least about -1.0 ± 9.4 U / L over a period of about 78 days after the following administrations, wherein the administrations are (i) a dose of the drug containing 450 μg of GL0034 administered to the subject once a week for two weeks, (ii) a dose of the drug containing 900 μg of GL0034 administered to the subject once a week for two weeks, and (iii) a dose of the drug containing 1520 μg of GL0034 administered to the subject once a week for four weeks, as described in Embodiment 410. Embodiment 420: The change in AST levels from baseline is at least about -4.0 ± 7.5 U / L over a period of about 51 days after administration, wherein the administration is (i) a dose of the drug containing 450 μg of GL0034 administered to the subject once a week for two weeks, (ii) a dose of the drug containing 900 μg of GL0034 administered to the subject once a week for two weeks, and (iii) a dose of the drug containing 1520 μg of GL0034 administered to the subject once a week for four weeks, as described in Embodiment 410. Embodiment 421: The change in AST levels from baseline is at least about -1.1 ± 6.7 U / L over a period of about 78 days after the following administrations, wherein the administrations are (i) doses of the drug containing 450 μg of GL0034 administered to the subject once a week for two weeks, (ii) doses of the drug containing 900 μg of GL0034 administered to the subject once a week for two weeks, and (iii) doses of the drug containing 1520 μg of GL0034 administered to the subject once a week for four weeks, as described in Embodiment 410. Embodiment 422: The change in GGT levels from baseline is at least about -3.4 ± 3.5 U / L over a period of about 51 days after the following administrations, wherein the administrations are (i) doses of the drug containing 450 μg of GL0034 administered to the subject once a week for two weeks, (ii) doses of the drug containing 900 μg of GL0034 administered to the subject once a week for two weeks, and (iii) doses of the drug containing 1520 μg of GL0034 administered to the subject once a week for four weeks, as described in Embodiment 410. Embodiment 423: The change in GGT levels from baseline is at least about -1.0 ± 2.7 U / L over a period of about 78 days following the administration, wherein the administration is (i) a dose of the drug containing 450 μg of GL0034, administered to the subject once a week for two weeks; (ii) a dose of the drug containing 900 μg of GL0034, administered to the subject once a week for two weeks; and (iii) a dose of the drug containing 1520 μg of GL0034, administered to the subject once a week for four weeks, as described in Embodiment 410. Embodiment 424: The change in body weight from baseline was at least about -3.4 ± 1.8 kg over a period of about 29 days after administration of a dose of the drug containing 450 μg of GL0034, as described in Embodiment 410, where the drug is administered to the subject once a week for a period of 4 weeks. Embodiment 425: The change in body weight from baseline was at least about -4.1 ± 1.0 kg over a period of about 29 days after administration of a dose of the drug containing 680 μg of GL0034, as described in Embodiment 410, where the drug is administered to the subject once a week for a period of 4 weeks. Embodiment 426: The change in body weight from baseline is at least about -7.7 ± 1.9 kg over a period of about 52 days after the following administrations, wherein the administrations are (i) a dose of the drug containing 450 μg of GL0034, administered to the subject once a week for two weeks; (ii) a dose of the drug containing 900 μg of GL0034, administered to the subject once a week for two weeks; and (iii) a dose of the drug containing 1520 μg of GL0034, administered to the subject once a week for four weeks, as described in Embodiment 410. Embodiment 427: The change in body weight from baseline is at least about -6.4 ± 2.1 kg over a period of about 78 days after the following administrations, wherein the administrations are (i) a dose of the drug containing 450 μg of GL0034, administered to the subject once a week for two weeks; (ii) a dose of the drug containing 900 μg of GL0034, administered to the subject once a week for two weeks; and (iii) a dose of the drug containing 1520 μg of GL0034, administered to the subject once a week for four weeks, as described in Embodiment 410. Embodiment 428: The change in %HbA1c from baseline is at least about -0.25 ± 0.2 over a period of about 78 days after the following administrations, wherein the administrations are (i) a dose of the drug containing 450 μg of GL0034 administered to the subject once a week for two weeks, (ii) a dose of the drug containing 900 μg of GL0034 administered to the subject once a week for two weeks, and (iii) a dose of the drug containing 1520 μg of GL0034 administered to the subject once a week for four weeks, as described in Embodiment 410. Embodiment 429: The change in TG levels from baseline is at least about -21.0 ± 27.5 mg / dL over a period of about 51 days after the following administrations, wherein the administrations are (i) a dose of the drug containing 450 μg of GL0034 administered to the subject once a week for two weeks, (ii) a dose of the drug containing 900 μg of GL0034 administered to the subject once a week for two weeks, and (iii) a dose of the drug containing 1520 μg of GL0034 administered to the subject once a week for four weeks, as described in Embodiment 410. Embodiment 430: The change in TG levels from baseline is at least about -11.0 ± 55.3 mg / dL over a period of about 78 days after the following administrations, wherein the administrations are (i) a dose of the drug containing 450 μg of GL0034 administered to the subject once a week for two weeks, (ii) a dose of the drug containing 900 μg of GL0034 administered to the subject once a week for two weeks, and (iii) a dose of the drug containing 1520 μg of GL0034 administered to the subject once a week for four weeks, as described in Embodiment 410. Embodiment 431: The change in TC level from baseline is at least about -29.1 ± 23.3 mg / dL over a period of about 51 days after the following administrations, wherein the administrations are (i) a dose of the drug containing 450 μg of GL0034 administered to the subject once a week for two weeks, (ii) a dose of the drug containing 900 μg of GL0034 administered to the subject once a week for two weeks, and (iii) a dose of the drug containing 1520 μg of GL0034 administered to the subject once a week for four weeks, as described in Embodiment 410. Embodiment 432: The change in TC level from baseline is at least about -5.8 ± 12.6 mg / dL over a period of about 78 days after the following administrations, wherein the administrations are (i) a dose of the drug containing 450 μg of GL0034 administered to the subject once a week for two weeks, (ii) a dose of the drug containing 900 μg of GL0034 administered to the subject once a week for two weeks, and (iii) a dose of the drug containing 1520 μg of GL0034 administered to the subject once a week for four weeks, as described in Embodiment 410. Embodiment 433: The change in LDL level from baseline is at least about -24.0 ± 24.3 mg / dL over a period of about 51 days after administration, wherein the administration is (i) a dose of the drug containing 450 μg of GL0034, administered to the subject once a week for two weeks; (ii) a dose of the drug containing 900 μg of GL0034, administered to the subject once a week for two weeks; and (iii) a dose of the drug containing 1520 μg of GL0034, administered to the subject once a week for four weeks, as described in Embodiment 410. Embodiment 434: The change in LDL level from baseline is at least about -19.5 ± 35.8 mg / dL over a period of about 78 days after administration, wherein the administration is (i) a dose of the drug containing 450 μg of GL0034, administered to the subject once a week for two weeks; (ii) a dose of the drug containing 900 μg of GL0034, administered to the subject once a week for two weeks; and (iii) a dose of the drug containing 1520 μg of GL0034, administered to the subject once a week for four weeks, as described in Embodiment 410. Embodiment 435: The change in HDL levels from baseline is at least about 2.9 ± 3.1 mg / dL over a period of about 78 days after administration, wherein the administration is (i) a dose of the drug containing 450 μg of GL0034, administered to the subject once a week for two weeks; (ii) a dose of the drug containing 900 μg of GL0034, administered to the subject once a week for two weeks; and (iii) a dose of the drug containing 1520 μg of GL0034, administered to the subject once a week for four weeks, as described in Embodiment 410. Embodiment 436: The change in body weight from baseline is at least about -2.4 ± 2.2 kg over a period of about 22 days following administration of a single dose of the drug containing 1520 μg of GL0034, as described in Embodiment 410. Embodiment 437: The change in body weight from baseline is at least about -1.8 ± 2.4 kg over a period of about 22 days following administration of a single dose of the drug containing 2000 μg of GL0034, as described in Embodiment 410. Embodiment 438: The change in body weight from baseline is at least about -3.1 ± 1.7 kg over a period of about 22 days following administration of a single dose of the drug containing 2520 μg of GL0034, as described in Embodiment 410. Embodiment 439: The agent according to Embodiment 410, wherein the change in TG levels from baseline is at least about -0.4 ± 0.4 mmol / L over a period of about 8 days following administration of a single dose of the agent containing 1520 μg of GL0034. Embodiment 440: The change in TG levels from baseline is at least about -0.8 ± 0.5 mmol / L over a period of about 8 days following administration of a single dose of the drug containing 2000 μg of GL0034, as described in Embodiment 410. Embodiment 441: The change in TG levels from baseline is at least about -0.5 ± 0.5 mmol / L over a period of about 22 days following administration of a single dose of the drug containing 2520 μg of GL0034, as described in Embodiment 410. Embodiment 442: The change in leptin levels from baseline is at least about -6.9 ± 5.1 ng / mL over a period of about 8 days following administration of a single dose of the drug containing 1520 μg of GL0034, as described in Embodiment 410. Embodiment 443: The change in leptin levels from baseline is at least about -10.9 ± 8.6 ng / mL over a period of about 8 days following administration of a single dose of the drug containing 2000 μg of GL0034, as described in Embodiment 410. Embodiment 444: The change in leptin levels from baseline is at least about -11.6 ± 12.8 ng / mL over a period of about 8 days following administration of a single dose of the drug containing 2520 μg of GL0034, as described in Embodiment 410. Embodiment 445: The use according to either Embodiment 385 or Embodiment 386, wherein an initial dose of a drug containing approximately 450 μg or approximately 680 μg of GL0034 is administered to the subject for at least approximately two weeks, an escalating dose of a drug containing approximately 680 μg or approximately 900 μg of GL0034 is administered to the subject once a week for at least approximately two weeks, and a maintenance dose of a drug containing approximately 1520 μg or approximately 2000 μg of GL0034 is administered to the subject once a week for at least approximately four weeks. Embodiment 446: The use according to either Embodiment 385 or Embodiment 386, wherein an initial dose of a drug containing approximately 450 μg or approximately 680 μg of GL0034 is administered to the subject for at least approximately 4 weeks, and escalating doses of a drug containing approximately 680 μg or approximately 900 μg of GL0034 are administered to the subject once a week for at least approximately 2 weeks. Embodiment 447: The use according to either Embodiment 385 or Embodiment 386, wherein an initial dose of a drug containing approximately 450 μg or approximately 680 μg of GL0034 is administered to the subject for at least approximately 4 weeks, an escalating dose of a drug containing approximately 680 μg or approximately 900 μg of GL0034 is administered to the subject once a week for at least approximately 2 weeks, and a maintenance dose of a drug containing approximately 1520 μg or approximately 2000 μg of GL0034 is administered to the subject once a week for at least approximately 2 weeks. [Examples]

[0063] The following examples illustrate specific embodiments of the Disclosure and various uses thereof. They are provided for illustrative purposes only and should not be construed as limiting the scope of the Disclosure in any way.

[0064] GL0034 was administered subcutaneously to the abdominal wall. The qualitative and quantitative composition is as follows: [Table 1]

[0065] Example 1: Safety, tolerability, pharmacodynamics, and pharmacokinetics of GL0034 in normal weight subjects. A randomized, double-blind, placebo-controlled trial was conducted to evaluate the safety and tolerability of GL0034 after single and repeated escalating subcutaneous administration in healthy volunteers. Repeated escalating administration of GL0034 was performed on healthy young men (approximately 18-28 kg / m²). 2 It was administered by subcutaneous injection to subjects with a BMI of [specific BMI].

[0066] Nine healthy male subjects (aged 18-40) received GL0034 as a subcutaneous injection into the abdomen at various dose levels, while three subjects received a placebo. Eighteen subjects received four doses at one-week intervals, and nine subjects received eight doses at one-week intervals. In total, 27 healthy subjects received repeated doses of GL0034, while nine subjects received a placebo.

[0067] Participants were randomly assigned to receive one of three different treatments, as follows: Group 1: GL0034 (450 μg) or placebo, administered once weekly as a single subcutaneous injection into the abdominal wall for 4 weeks. Group 2: GL0034 (680 μg) or placebo as a single subcutaneous injection into the abdominal wall once a week for 4 weeks, or Group 3: Two doses of GL0034 (450 μg) or placebo administered as a single subcutaneous injection into the abdominal wall once a week for two weeks. This was followed by two doses of GL0034 (900 μg) or placebo administered as a single subcutaneous injection into the abdominal wall once a week for two weeks. This was followed by four doses of GL0034 (1520 μg) or placebo administered as a single subcutaneous injection into the abdominal wall once a week for four weeks, according to a two-stage escalation scheme (i.e., eight doses over eight weeks with one-week intervals).

[0068] The safety and tolerability of repeated dose escalations of GL0034 were determined in groups 1-3, further demonstrated according to the timeline described above and shown in Figure 1. Safety biomarkers, including fasting insulin and glucose, alanine transaminase, and body weight, as well as key exploratory pharmacodynamic effects, were evaluated.

[0069] result Adverse effects associated with GL0034 were gastrointestinal, including dose-dependent nausea, vomiting, and decreased appetite. Fasting insulin levels (Table 1) decreased in groups 2 and 3 at days 23 and 51, respectively, after treatment with GL0034, corresponding to a decrease in the homeostasis model assessment of insulin resistance (HOMA-IR) (Figures 4 and 5). At day 51, alanine transaminase levels decreased from baseline in group 3 compared to the increase in placebo (Figure 3, Table 1). Dose-dependent weight loss compared to baseline was measured in all groups and persisted until days 50 and 78 (Figure 2). These results support the well-tolerated and effective use of GL0034 in healthy individuals with normal body weight. The results are summarized in Table 1. [Table 2]

[0070] Example 2: Pharmacodynamic (PD) and safety results of MASLD / MASH in a Phase 1 repeated dose escalation study in healthy subjects. A randomized, double-blind, placebo-controlled trial was conducted to evaluate the safety and tolerability of GL0034 after single and repeated escalation subcutaneous administration in healthy volunteers. Repeated escalation of GL0034 was administered to healthy young men (approximately 18-28 kg / m²). 2 It was administered by subcutaneous injection to subjects with a BMI of [specific BMI].

[0071] Nine healthy male subjects (aged 18-40) received GL0034 as a subcutaneous injection into the abdomen at various dose levels, while three subjects received a placebo. Eighteen subjects received four doses at one-week intervals, and nine subjects received eight doses at one-week intervals. In total, 27 healthy subjects received repeated doses of GL0034, while nine subjects received a placebo.

[0072] Participants were randomly assigned to receive one of three different treatments, as follows: Group 1: GL0034 (450 μg) or placebo, administered once weekly as a single subcutaneous injection into the abdominal wall for 4 weeks. Group 2: GL0034 (680 μg) or placebo as a single subcutaneous injection into the abdominal wall once a week for 4 weeks, or Group 3: Two doses of GL0034 (450 μg) or placebo administered as a single subcutaneous injection into the abdominal wall once a week for two weeks. This was followed by two doses of GL0034 (900 μg) or placebo administered as a single subcutaneous injection into the abdominal wall once a week for two weeks. This was followed by four doses of GL0034 (1520 μg) or placebo administered as a single subcutaneous injection into the abdominal wall once a week for four weeks, according to a two-stage escalation scheme (i.e., eight doses over eight weeks with one-week intervals).

[0073] The safety and tolerability of repeated dose escalations of GL0034 were determined in groups 1-3 / cohorts 1-3, further demonstrated according to the timeline described above and shown in Figure 1. Safety biomarkers evaluated included body weight, glycated hemoglobin A1c (HbA1c), liver enzymes (alanine transaminase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT)), and lipid profiles (triglycerides, total cholesterol, high-density lipoprotein (HDL), and low-density lipoprotein (LDL)).

[0074] result GL0034 was generally well-tolerated, and associated adverse effects were mainly gastrointestinal, including dose-dependent nausea, vomiting, and decreased appetite. Despite the escalating dose of GL0034, adverse events became less frequent over time. Clinically significant changes were observed in body weight, HbA1c, and lipid profile compared to baseline (Table 2). Compared to placebo, GL0034 resulted in increased HDL (Table 2) and lower ALT, AST, and GGT levels (Table 2). [Table 3]

[0075] conclusion GL0034, a potent, long-acting GLP-1 receptor agonist, was safe and well-tolerated, improving liver function in healthy individuals. The observed PD effect reflects the therapeutic benefit in MASLD / MASH patients.

[0076] Tables 3-7 show that healthy young men (approximately 18-28 kg / m²) 2 This report presents various data from repeated dose escalation of GL0034 in individuals with a BMI of [BMI value].

[0077] Target data - Repeated dose escalation of GL0034 in healthy young men. [Table 4] [Table 5] [Table 6] [Table 7] [Table 8]

[0078] Example 3: Safety and tolerability of single dose escalation of GL0034 in obese subjects without diabetes. A four-part, randomized, double-blind, placebo-controlled trial was conducted in overweight and / or obese subjects. The safety, tolerability, pharmacodynamics, and pharmacokinetics of GL0034 were evaluated in healthy overweight and / or obese volunteers after single and repeated escalating subcutaneous doses (Figures 6 and 7).

[0079] A single dose of GL0034 is administered in overweight and / or obese (28 kg / m²) healthy young men. 2 The study involved subjects with the above BMI (Body Mass Index) and administered GL0034 by subcutaneous injection. Six healthy male subjects aged 18-40 years received intraperitoneal subcutaneous injections of GL0034 at various dose levels (1520 μg, 2000 μg, and 2520 μg per subject). Two subjects received placebo at each dose level. A total of 18 healthy overweight / obese male subjects received GL0034 as a single dose, and six subjects received placebo. The pharmacokinetics and key exploratory pharmacodynamic parameters (triglycerides, leptin levels, and body weight) of GL0034 were evaluated (Table 8).

[0080] result The most common adverse events associated with GL0034 were gastrointestinal tract symptoms, including dose-dependent nausea, decreased appetite, and vomiting. No injection site reactions or other adverse events were observed. The peak concentrations of GL0034 ranged from 227±57 to 367±152 ng / mL, and the mean half-life ranged from 99 to 118 hours. Triglyceride levels decreased from baseline on day 8 after treatment with GL0034 at doses of 2000 and 2520 μg (Figure 9). The decrease in leptin levels was dose-dependent (Figure 9). Weight loss compared to baseline reached a maximum of 3.3 kg on day 8 with the 2520 μg dose, and this effect persisted until day 22 with all GL0034 doses (Figure 8, Table 8).

[0081] In the combined data (n=18), 28% of participants achieved a weight loss of over 3% after a single dose of GL0034 on both days 8 and 22, compared to 0% change in participants who received placebo. Increases over time were observed, with 11% of participants experiencing a weight loss of over 5% on day 22. Significant decreases in triglycerides were also observed in all three cohorts. On day 8, decreases were 17.5%, 40.7%, and 28.0% in cohorts 1, 2, and 3, respectively, and on day 22, decreases were 21.2%, 25.4%, and 12.5%. In contrast to the three cohorts, participants who received placebo experienced increases in triglycerides of 9.9% and 7.6% on days 8 and 22, respectively. TG levels (mg / dL) above 150 mg / dL at baseline (n=9) also showed a robust decrease. In subjects with a baseline glucose level of 194.7±29.1 mg / dL, a 38.9% reduction (p<0.05 compared to placebo) was observed on day 8, while in subjects with a baseline value of 212±100.8 mg / dL (n=4), a 4.1% reduction was observed compared to placebo. The reduction in area under the glucose curve during the OGTT on day 8 was 16.7% (p<0.05), 21.5% (p<0.01), and 26.4% (p<0.05) in the three cohorts, respectively, compared to only a 7.4% reduction in the placebo group. [Table 9]

[0082] conclusion In conclusion, once-weekly administration of GL0034 was well-tolerated and demonstrated clinically relevant reductions in body weight, triglycerides, and area under the glucose curve during oral glucose tolerance tests (OGTT) in obese individuals.

[0083] Example 4: Safety and tolerability of single dose escalation of GL0034 in obese subjects. A four-part, randomized, double-blind, placebo-controlled trial was conducted in overweight and / or obese subjects. The safety, tolerability, pharmacodynamics, and pharmacokinetics of GL0034 were evaluated in healthy overweight and / or obese volunteers after single and repeated dose-escalating subcutaneous administration.

[0084] A single dose of GL0034 is administered in overweight and / or obese (30 kg / m²) healthy young men. 2 The drug was administered by subcutaneous injection to subjects with the above BMI. Six healthy male subjects aged 18-40 years received intraperitoneal subcutaneous injections of GL0034 at each dose level (1520 μg, 2000 μg, and 2520 μg per subject). Two subjects received placebo at each dose level. A total of 18 healthy overweight / obese male subjects received a single dose of GL0034, and 6 subjects received placebo. The pharmacokinetics and key exploratory pharmacodynamic parameters (triglycerides, leptin levels, and body weight) of GL0034 were evaluated (Table 9).

[0085] result No safety concerns were identified with GL0034, and tolerability was limited to dose-dependent gastrointestinal events, including nausea, decreased appetite, and vomiting, and the effects of the GLP-1 receptor agonist class. Weight loss from baseline (BL) was observed on day 8 [res) 2.4±1.3 (p<0.01), 2.2±1.1 (p<0.05), 3.3±1.9 (p<0.01), compared to PB -0.3±0.5kg] and on day 15 [res] 1.7±1.6 (p<0.05), 2.4±2.0 (p<0.05), 2.7±1.9 (p<0.05), compared to PB -0.1±2.0kg (BL BMI was (res) 34.5±3.0, 34.4±4.0, 38.9±7.3, and 31.8±3.1 kg / m², respectively). 2 )] was observed.

[0086] Lipid changes were observed on day 8, with triglycerides [(res) -42.2±48.3, -44.7±43.7, -18.7±46.9 respectively, compared to PB at 24.5±71.0 mg / dL] and total cholesterol [(res) -23.7±11.2, -28.5±19.1 (p<0.01), -27.8±31.5 respectively, compared to PB at -3.7±10.2 mg]. On day 15, the levels of TG / HDL [(res) -19.0±10.6, -23.8±21.5 (p<0.05), -28.0±25.3, respectively, compared to PB at -6.3±2.6 mg / dL], and HDL [(res) -6.0±2.3 (p<0.01), -3.7±5.9, -1.8±3.3, compared to PB at -0.2±3.4 mg / dL] were measured. On day 15, the TG / HDL ratio of the treated patients improved, changing from the BL ratios (res) 3.6±1.6, 4.1±1.7, 4.5±2.3, compared to PB at 4.5±2.9, to (res) 3.1±1.4, 3.1±1.0, 4.3±3.2, compared to PB at 5.3±4.3. [Table 10]

[0087] conclusion GL0034 administered once a week is safe and well-tolerated in obese adults. At all maintenance doses, GL0034 reduced body weight in obese individuals, showed beneficial effects on lipid profiles, and improved the TG / HDL ratio. The TG / HDL ratio is a predictor of many potential clinical conditions. Clinically, an improvement in the TG / HDL ratio may lead to a reduced risk of heart attack and stroke, an improved atherosclerotic lipid profile, and therefore a reduced risk of developing coronary artery disease such as coronary atherosclerosis, as well as a reduced risk of cerebrospinal fluid disorders such as silent stroke.

[0088] Tables 10-13 below provide summaries of various datasets. [Table 11] [Table 12] [Table 13] [Table 14]

[0089] Example 5: Safety and tolerability of repeated dose escalation of GL0034 in obese subjects. A double-blind, placebo-controlled trial was conducted in obese subjects. Tolerability and metabolic effects were evaluated in obese subjects after repeated dose escalations of GL0034.

[0090] Repeated dose escalation of GL0034 is used in healthy young obese men (BMI ≥ 28 kg / m²). 2The drug was administered to the subjects by subcutaneous injection. Two cohorts of nine subjects each received GL0034 treatment, while three subjects in each cohort received placebo. Cohort 1 received a single dose of 680 μg once a week for four weeks, while Cohort 2 received gradually increasing doses of 680 μg, 900 μg, 1520 μg, and 2000 μg over four weeks. Safety, tolerability, and metabolic effects after GL0034 treatment were evaluated.

[0091] result The most common adverse events (AEs) were dose-dependent gastrointestinal (GI) reactions including nausea, decreased appetite, and vomiting. One individual with a severe GI-related AE recovered rapidly with intravenous fluid therapy. On day 23, a decrease from baseline (BL) was observed in all parameters. Significant decreases included area under the glucose curve (177.5 ± 12.1 mg*h / dL) and HbA1c percentage in both groups. Cohort 1 experienced a decrease of 5.3 ± 0.4%, and Cohort 2 experienced a decrease of 4.9 ± 0.1%. In Cohorts 1 and 2, the decrease from BL on day 29 was 2.9 kg and 4.6 kg, respectively (Table 14). The complete findings of this study are shown in Table 14 below. [Table 15]

[0092] conclusion GL0034 administered once a week was found to be safe and well-tolerated in obese adults. GL0034 reduced body weight, decreased glucose AUC in the OGTT, and lowered HbA1c levels in individuals treated with GL0034. These results lead to controlled diabetes and lower blood glucose levels, which are indicators of weight loss, and are important metrics in reducing chronic inflammatory conditions exacerbated by obesity.

[0093] Example 6: Phase 1 repeated dose escalation (MAD) study of GL0034 in obese individuals Subjects: A randomized, double-blind, placebo-controlled trial was conducted to evaluate the safety, tolerability, and pharmacodynamics of the repeated dose escalation study. BMI ≥ 28 kg / m² 2 Individuals with (n=12) were randomized to receive subcutaneous escalating doses of GL once weekly for 4 weeks (680, 900, 1520, or 2000 μg) or placebo (9:3). Biomarker measurements included body weight, lipid profiles (triglycerides (TG), total cholesterol (TC), and low-density lipoprotein (LDL)), liver enzymes (alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT)), free fatty acids (FFA), homeostasis model assessment of insulin resistance (HOMA-IR), and leptin.

[0094] result The most common adverse events (AEs) were dose-dependent gastrointestinal (GI) reactions including nausea, decreased appetite, and vomiting. One individual with a severe GI-related AE recovered rapidly with intravenous fluid therapy. The mean baseline BMI (kg / m2) was 32.4 ± 4.6 kg / m2 in the GL0034 treatment group. 2 In the placebo group, the average weight was 27.9 ± 1.3 kg / m². 2The subjects lost 4.6±1.5 kg (p<0.001) on day 29 compared to the placebo group (0.0±0.9 kg). Consistently, the GL0034-treated subjects also showed a significant decrease in triglycerides. On day 23, the subjects showed a decrease of 47.1±54.2 mg / dL from baseline (p<0.05) compared to a decrease of 16.7±28.7 mg / dL in the placebo group. Furthermore, total cholesterol decreased by 20.0±26.8 mg / dL compared to 8.7±26.9 mg / dL in the placebo group, and LDL levels similarly decreased by 5.7±23.9 mg / dL, while the placebo group experienced an increase of 11.3±19.6 mg / dL from baseline. Decreases in ALT, AST, and GGT were also achieved with GL0034 treatment. ALT levels decreased by 9.1 U / L (±13.9 U / L) in the GL0034 group compared to the placebo group, which experienced an increase of 6.3 U / L (±43 U / L). AST levels decreased by 2.7 U / L (±4.2 U / L), in contrast to an increase of 1.7 U / L (±18.7 U / L) in the placebo group. On day 23, the decrease in GGT from baseline was 4.2 U / L (±2.4 U / L, p<0.001), compared to an increase of 4.3 U / L (±15.3 U / L) in the placebo group, which was statistically significant compared to the placebo group. There were no changes in free fatty acid levels in either the GL0034 or placebo group. HOMA-IR improved from baseline 2.3 (±1.2) to 1.7 (±1.0) and 1.7 (±0.4) on days 23 and 50, respectively. Baseline leptin levels in the placebo group were 3.2 (±0.5) to 2.1 (±0.1) and 2.6 (±0.9) on days 23 and 50, respectively. Finally, a decrease in leptin was observed on days 23 and 50. The treated subjects showed decreases of 5.7 (±5.9) and 4.5 (±10.2) on days 23 and 50, compared to a decrease of 3.7 (±5.3) and an increase of 5.1 (±16.4) in the placebo group.

[0095] conclusion GL0034, a potent and long-acting GLP-1RA, was safe and well-tolerated. Treatment with GL0034 resulted in significant weight loss and improvement in lipid, liver damage, and metabolic biomarkers in obese individuals. The observed PD effects suggest potential therapeutic benefits in MASLD patients.

[0096] Example 7: A study to evaluate the efficacy of GLP-1 analog after repeated subcutaneous injections in db / db mice. material and method Male / female db / db (C57BL / KsJ-db / db) mice (8-10 weeks old, 45-65g body weight), procured from the Laboratory Animal Resources Department of Sun Pharma Advanced Research Company Ltd., were housed in individual ventilated cages with free access to food and water, and maintained on a 12-hour / 12-hour light-dark cycle. The mice were acclimatized for 3 days. On day 0, each animal was weighed using a digital balance, and 10 μL of blood was collected by posterior orbital venous plexus puncture under mild isoflurane anesthesia. Blood glucose levels were measured using a handheld blood glucose meter (One Touch Ultra®; LIFESCAN, Johnson & Johnson, Malburn, Pennsylvania), and %HbA1c was measured using the A1CNow+® kit (PTS Diagnostics, Indianapolis, Indiana). Mice were divided into treatment groups (n=8 per group, 4 males and 4 females) matched for baseline HbA1c levels. The mice were subcutaneously injected into the neck region every three days for four weeks using a vehicle, GL0034 (21 nmol / kg), semaglutide (21 nmol / kg), or tilzepatide (21 nmol / kg).

[0097] Body weight and food intake were continuously monitored. Blood samples were taken on days 14 and 28 of the study, 24 hours after the final dose, to measure HbA1c and insulin levels.

[0098] On day 28, mice were sacrificed (n=5) after blood collection for measurement of HbA1c, insulin, C-peptide and glucagon, triglycerides, total cholesterol, low-density cholesterol (LDL), and amylase. The liver was removed for measurement of fibroblast growth factor-21 (FGF-21), while white adipose tissue and brown adipose tissue (WAT, BAT) were removed for estimation of uncoupling protein-1 levels (UCP-1).

[0099] Statistical comparisons were performed using one-way ANOVA, or two-way ANOVA as needed. Bonferroni post-hoc tests were used. A P value of <0.05 was assigned to statistical significance. Data are expressed as mean ± standard deviation (SD).

[0100] result Compared to the major glucagon-like peptide-1 receptor agonists, semaglutide and tirzepatide, GL0034 showed a strong trend towards a decrease in HbA1c percentage and an increase in the rate of change in body weight on days 14 and 28. These changes were statistically significant compared to semaglutide treatment. Similar trends were observed for decreases in glucagon, triglycerides, total cholesterol, and LDL on day 28. The insulin secretion response was better with GL0034 compared to semaglutide and tirzepatide on days 14 and 28. Increases in FGF-21 protein and UCP-1 in the liver in BAT and WAT were significantly higher than those observed with semaglutide. The increase in UCP-1 in BAT was significantly higher compared to both semaglutide and tirzepatide. The complete results of this study are shown in Table 15 below. [Table 16]

[0101] conclusion GL0034 showed a potent antidiabetic effect in db / db mice compared to semaglutide and tilzepatide, indicating that GL0034 may act as a GLP-1 RA in obese type 2 diabetic patients, as evidenced by a significant increase in UCP-1 levels in brown adipose tissue.

[0102] Example 8: Reduced blood pressure, lipids, and weight in postmenopausal women with utreglutide (GL0034) administered once weekly at a dose of 4 × 450 μg. In a randomized, double-blind, placebo-controlled trial, 12 postmenopausal women aged 18–65 years with an overweight / obese body mass index (BMI) ≥ 26 kg / m² were randomized to receive either a fixed dose of subcutaneous utreglutide (4 × 450 μg) once weekly for four weeks or placebo (9:3). Safety, tolerability, and key cardiac metabolic parameters were evaluated.

[0103] Biomarker measurements included area under the curve (AUC) for insulin and glucose in oral glucose tolerance tests (OGTT), systolic and diastolic blood glucose levels, lipid profiles (triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL), and non-high-density lipoprotein (non-HDL)), creatinine, potassium, blood glucose (BW), and leptin.

[0104] result Utreglutide was well-tolerated, and associated adverse effects were primarily gastrointestinal, including dose-dependent nausea, vomiting, and decreased appetite. Decrease in the AUC of the OGTT for insulin (p<0.05) and glucose (p<0.01) was recorded on day 23 after 4 weeks of utreglutide treatment. This was accompanied by a decrease in mean systolic and diastolic blood pressure (p<0.001) from baseline (BL) at day 23. Significant decreases in TC (p<0.01), LDL (p<0.05), and non-HDL (p<0.05) were observed on day 23. The decrease in BW (body weight) from BL (baseline) (p<0.001) was 2.0 kg and 1.8 kg at day 29 and end of study (EoS), respectively. Leptin levels were significantly reduced from BL on day 23 (p<0.01) and EoS (p<0.001). No significant changes were observed in TG, creatinine, or potassium (see Table 16). [Table 17]

[0105] conclusion In overweight and obese postmenopausal women, utreglutide administered once weekly at a dose of 450 μg over a four-week period demonstrated clinically relevant reductions in systolic and diastolic blood pressure. This was associated with improved performance in insulin and glucose OGTT AUC, lipids, body weight (BW), and leptin, demonstrating benefits to cardiac metabolism with high tolerability.

[0106] While the subject matter of this disclosure has been described in detail, it will be apparent by referring to the specific embodiments thereof that modifications and variations are possible without departing from the scope of the subject matter described in the claims.

Claims

1. A pharmaceutical composition comprising GL0034 for the treatment of obesity in a subject.

2. The pharmaceutical composition according to claim 1, wherein the subject is not diabetes.

3. The aforementioned subjects have a body mass index (BMI) of at least 28 kg / m². ２ It is either ≥ 27 kg / m ２ A pharmaceutical composition according to claim 1 or claim 2, wherein the patient has at least one weight-related comorbidity.

4. A pharmaceutical composition comprising GL0034 for the treatment of metabolic disorders in a subject.

5. The pharmaceutical composition according to claim 4, wherein the metabolic disorder is metabolic dysfunction-related fatty liver disease (MASLD).

6. The pharmaceutical composition according to claim 5, wherein the MASLD is metabolic dysfunction-associated steatohepatitis (MASH).

7. The pharmaceutical composition according to claim 4, wherein the metabolic disorder is diabetes mellitus or hypertriglyceridemia.

8. The pharmaceutical composition according to claim 7, wherein the metabolic disorder is type 2 diabetes.

9. The subject is a person having high blood pressure, and the pharmaceutical composition is according to any one of claims 1 to 8.

10. The pharmaceutical composition according to any one of claims 1 to 9, which is administered subcutaneously to the subject.

11. The pharmaceutical composition according to claim 10, wherein the pharmaceutical composition is administered to the subject by subcutaneous injection.

12. The pharmaceutical composition according to claim 11, wherein the pharmaceutical composition is administered to the subject using an auto-injector or a pre-filled syringe.

13. The pharmaceutical composition according to any one of claims 1 to 12, wherein the dosage of the pharmaceutical composition contains 200 μg to 8000 μg of GL0034.

14. The pharmaceutical composition according to claim 13, wherein the dose of the pharmaceutical composition comprises 300 μg to 6000 μg of GL0034.

15. The pharmaceutical composition according to claim 14, wherein the dose of the pharmaceutical composition comprises 400 μg to 4000 μg of GL0034.

16. The pharmaceutical composition according to claim 15, wherein the dose of the pharmaceutical composition comprises 1,000 μg to 3,000 μg of GL0034.

17. The pharmaceutical composition according to any one of claims 1 to 16, wherein the dose of the pharmaceutical composition is administered to the subject once a week or once every two weeks.

18. The administration of the pharmaceutical composition to the subject is to the average maximum concentration (C) of GL0034, which is between 75 ng / mL and 1200 ng / mL. ｍａｘ A pharmaceutical composition according to any one of claims 1 to 16, which brings about ).

19. The area under the concentration-time curve (AUC) of GL0034 when the administration of the pharmaceutical composition to the subject is 6200 ng*h / mL to 406300 ng*h / mL over a period of 22 days. ０－ｔ A pharmaceutical composition according to any one of claims 1 to 16, which brings about ).

20. The pharmaceutical composition according to claim 16, wherein the dose of the pharmaceutical composition comprises 1520 μg, 2000 μg, or 2520 μg of GL0034.

21. The administration of the pharmaceutical composition to the subject results in an average maximum concentration (C) of GL0034 ranging from 227 ng / mL to 367 ng / mL. ｍａｘ The pharmaceutical composition according to claim 20, which brings about ).

22. The area under the concentration-time curve (AUC) of GL0034 is such that the administration of the pharmaceutical composition to the subject is 30313 ng*h / mL to 83082 ng*h / mL over a period of 22 days. ０－ｔ The pharmaceutical composition according to claim 20, which brings about ).

23. The administration of the pharmaceutical composition to the subject is 90 to 120 hours, and the plasma drug half-life (t) of GL0034 is 90 to 120 hours. １／２ A pharmaceutical composition according to any one of claims 1 to 21, which brings about ).

24. The administration of the pharmaceutical composition to the subject is 98 to 113 hours, and the plasma drug half-life (t) of GL0034 is 98 to 113 hours. １／２ The pharmaceutical composition according to claim 21, which brings about ).

25. The pharmaceutical composition according to any one of claims 1 to 12, wherein the pharmaceutical composition is administered to the subject once a week or once every two weeks.

26. The pharmaceutical composition according to any one of claims 1 to 12 or 25, wherein the dosage of the pharmaceutical composition includes 450 μg, 680 μg, 900 μg, 1520 μg, 2000 μg, or 2520 μg of GL0034.

27. The pharmaceutical composition according to claim 26, wherein the dose of the pharmaceutical composition is administered once a week or once every two weeks.

28. The dosage of the pharmaceutical composition includes 450 μg of GL0034, and administration of the pharmaceutical composition to the subject once a week for at least 4 weeks results in an average peak concentration (C ｍａｘ ) of GL0034 that is 101 ng / mL to 142 ng / mL. The pharmaceutical composition according to claim 26.

29. The area under the concentration-time curve (AUC) of GL0334 when the administration of the pharmaceutical composition to the subject is 12814 ng*h / mL to 18537 ng*h / mL over a period of 22 days. ０－ｔ The pharmaceutical composition according to claim 28, which brings about ).

30. The administration of the pharmaceutical composition to the subject results in a plasma drug half-life (t) of GL0034 of 102 hours by the 22nd day. １／２ The pharmaceutical composition according to claim 28, which brings about ).

31. The dose of the pharmaceutical composition comprises 680 μg of GL0034, and the administration of the pharmaceutical composition to the subject once a week for at least four weeks results in an average maximum concentration (C) of GL0034 between 169 ng / mL and 267 ng / mL. ｍａｘ The pharmaceutical composition according to claim 26, which brings about ).

32. The area under the concentration-time curve (AUC) of GL0034 when the administration of the pharmaceutical composition to the subject is 24576 ng*h / mL to 34537 ng*h / mL over a period of 22 days. ０－ｔ The pharmaceutical composition according to claim 31, which brings about ).

33. Administration of the pharmaceutical composition to the subject results in a plasma drug half-life (t) of GL0034 of 122.9 ± 16.5 hours by day 22. １／２ The pharmaceutical composition according to claim 31, which brings about ).

34. (i) a dose of the pharmaceutical composition containing 50 μg to 200 μg of GL0034 is administered to the subject once a week for at least two weeks; (ii) a dose of the pharmaceutical composition containing 200 μg to 400 μg of GL0034 is administered to the subject once a week for at least two weeks; (iii) a dose of the pharmaceutical composition containing 500 μg to 700 μg of GL0034 is administered to the subject once a week for at least two weeks; (iv) a dose of the pharmaceutical composition containing 1200 μg to 1500 μg of GL0034 is administered to the subject once a week for at least two weeks; and (v) a dose of the pharmaceutical composition containing 2000 μg to 3000 μg of GL0034 is administered to the subject once a week for at least four weeks, according to any one of claims 1 to 12.

35. (i) a dose of the pharmaceutical composition containing 450 μg of GL0034 is administered to the subject once a week for at least two weeks; (ii) a dose of the pharmaceutical composition containing 900 μg of GL0034 is administered to the subject once a week for at least two weeks; and (iii) a dose of the pharmaceutical composition containing 1520 μg of GL0034 is administered to the subject once a week for at least four weeks, according to any one of claims 1 to 12.

36. The administration of the pharmaceutical composition to the subject results in an average maximum concentration (C) of GL0034 ranging from 112 ng / mL to 708 ng / mL. ｍａｘ The pharmaceutical composition according to claim 35, which brings about ).

37. The area under the concentration-time curve (AUC) of GL0034 when the administration of the pharmaceutical composition to the subject is 12942 ng*h / mL to 76320 ng*h / mL over a period of 50 days. ０－ｔ The pharmaceutical composition according to claim 35, which brings about ).

38. Administration of the pharmaceutical composition to the subject results in a plasma drug half-life (t) of GL0034 of 106.8 ± 33.7 hours by day 50. １／２ The pharmaceutical composition according to claim 35, which brings about ).

39. (i) an initial dose of the pharmaceutical composition containing 200 μg to 680 μg of GL0034 is administered to the subject for at least four weeks; (ii) an increasing dose of the pharmaceutical composition containing 680 μg to 900 μg of GL0034 is administered to the subject once a week for at least two weeks; and (iii) a maintenance dose of the pharmaceutical composition containing 1500 μg to 2000 μg of GL0034 is administered to the subject once a week for at least two weeks, according to any one of claims 1 to 12.

40. (i) an initial dose of the pharmaceutical composition comprising 450 μg to 680 μg of GL0034 is administered to the subject for at least four weeks, and (ii) an increasing dose of the pharmaceutical composition comprising 680 μg to 900 μg of GL0034 is administered to the subject once a week for at least two weeks, according to any one of claims 1 to 12.

41. (i) an initial dose of the pharmaceutical composition containing 450 μg to 680 μg of GL0034 is administered to the subject for at least four weeks; (ii) an increasing dose of the pharmaceutical composition containing 680 μg to 900 μg of GL0034 is administered to the subject once a week for at least two weeks; and (iii) a maintenance dose of the pharmaceutical composition containing 1520 μg to 2000 μg of GL0034 is administered to the subject once a week for at least two weeks, according to any one of claims 1 to 12.

42. Administration of the pharmaceutical composition to the subject results in one or more clinically significant changes from baseline in the subject, and these clinically significant changes from baseline include a decrease in alanine transaminase (ALT) levels, a decrease in aspartate aminotransferase (AST) levels, a decrease in gamma-glutamyltransferase (GGT) levels, a decrease in fasting insulin levels, a decrease in fasting blood glucose levels, a decrease in glycated hemoglobin (%HbA1c), and an assessment of insulin resistance homeostasis (HOMA-I). The pharmaceutical composition according to any one of claims 1 to 41, wherein the reduction is R), weight loss, leptin level loss, triglyceride (TG) level loss, total cholesterol (TC) level loss, low-density lipoprotein (LDL) level loss, high-density lipoprotein (HDL) level loss, TG / HDL ratio loss, FGF-21 increase in the liver, uncoupling protein-1 (UCP-1) level in brown adipose tissue (BAT) and / or white adipose tissue (WAT), and / or blood pressure loss.

43. The pharmaceutical composition according to claim 42, wherein the reduction in ALT value from baseline persists for at least 23 days, at least 52 days, or at least 78 days after administration of the pharmaceutical composition to the subject.

44. (a) The change in ALT value from baseline is at least -9 U / L over a period of about 23 days after administration of a dose of the pharmaceutical composition containing 450 μg of GL0034 to the subject, or at least -3 U / L over a period of about 23 days after administration of a dose of the pharmaceutical composition containing 680 μg of GL0034 to the subject, (b) The change in ALT value is at least -7 U / L for a period of about 51 days after the following administration to the subject, or at least -1 U / L for a period of about 78 days, wherein the administration is (i) a dose of the pharmaceutical composition containing 450 μg of GL0034 once a week for at least two weeks, (ii) a dose of the pharmaceutical composition containing 900 μg of GL0034 once a week for at least two weeks, and (iii) a dose of the pharmaceutical composition containing 1520 μg of GL0034 once a week for at least four weeks, according to claim 42.

45. The pharmaceutical composition according to claim 42, wherein the reduction in AST value from baseline persists for at least 23 days, at least 51 days, or at least 78 days after administration of the pharmaceutical composition to the subject.

46. The pharmaceutical composition according to claim 42, wherein the change in AST value from baseline is at least -4 U / L over a period of about 51 days after the following administration to the subject, or at least -1 U / L over a period of about 78 days, the administration being (i) a dose of the pharmaceutical composition containing 450 μg of GL0034 once a week for at least two weeks, (ii) a dose of the pharmaceutical composition containing 900 μg of GL0034 once a week for at least two weeks, and (iii) a dose of the pharmaceutical composition containing 1520 μg of GL0034 once a week for at least four weeks.

47. The pharmaceutical composition according to claim 42, wherein the reduction in GGT value from baseline is sustained for at least 23 days, at least 51 days, or at least 78 days after administration of the pharmaceutical composition to the subject.

48. The pharmaceutical composition according to claim 42, wherein the change in the GGT value from baseline is at least -3 U / L over a period of about 51 days after the following administration to the subject, or at least -1 U / L over a period of about 78 days, the administration being (i) a dose of the pharmaceutical composition containing 450 μg of GL0034 once a week for at least two weeks, (ii) a dose of the pharmaceutical composition containing 900 μg of GL0034 once a week for at least two weeks, and (iii) a dose of the pharmaceutical composition containing 1520 μg of GL0034 once a week for at least four weeks.

49. The pharmaceutical composition according to claim 42, wherein the reduction in fasting insulin levels from baseline persists for at least 23 days, or at least 51 days, after administration of the pharmaceutical composition to the subject.

50. The pharmaceutical composition according to claim 42, wherein the change in fasting insulin levels from baseline is at least -5 pmol / L for a period of about 23 days after administration of 680 μg of GL0034 to the subject once weekly for at least 4 weeks, or at least -11 pmol / L for a period of about 51 days after the following administrations to the subject, the administrations being (i) a dose of the pharmaceutical composition containing 450 μg of GL0034 once weekly for at least 2 weeks, (ii) a dose of the pharmaceutical composition containing 900 μg of GL0034 once weekly for at least 2 weeks, and (iii) a dose of the pharmaceutical composition containing 1520 μg of GL0034 once weekly for at least 4 weeks.

51. The pharmaceutical composition according to claim 42, wherein the reduction in fasting glucose persists for at least 23 days or at least 51 days after administration of the pharmaceutical composition to the subject.

52. The aforementioned decrease in fasting glucose is at least -3 mg / dL for a period of approximately 23 days after administration to the subject of a dose of the pharmaceutical composition containing 450 μg of GL0034 once a week for at least 4 weeks, or at least -5 mg / dL for a period of approximately 23 days after administration to the subject of a dose of the pharmaceutical composition containing 680 μg of GL0034 once a week for at least 4 weeks, or the following administration to the subject The pharmaceutical composition according to claim 42, wherein the dose is at least -8 mg / dL over a period of approximately 51 days thereafter, and the dose is (i) a dose of the pharmaceutical composition containing 450 μg of GL0034 once a week for at least two weeks, (ii) a dose of the pharmaceutical composition containing 900 μg of GL0034 once a week for at least two weeks, and (iii) a dose of the pharmaceutical composition containing 1520 μg of GL0034 once a week for at least four weeks.

53. The pharmaceutical composition according to claim 42, wherein the weight loss is sustained for at least 8 days, at least 15 days, at least 22 days, at least 29 days, at least 50 days, at least 52 days, or at least 78 days after administration of the pharmaceutical composition to the subject.

54. (a) The weight loss is at least -2 kg over a period of about 22 days after administration of a dose of the pharmaceutical composition containing 2000 μg of GL0034 to the subject, or at least -2 kg over a period of about 22 days after administration of a dose of the pharmaceutical composition containing 1520 μg of GL0034 to the subject, or at least -3 kg over a period of about 22 days after administration of a dose of the pharmaceutical composition containing 2520 μg of GL0034 to the subject, or at least -3 kg over a period of about 29 days after administration of a dose of the pharmaceutical composition containing 450 μg of GL0034 to the subject once a week for at least 4 weeks, or at least -4 kg over a period of about 29 days after administration of a dose of the pharmaceutical composition containing 680 μg of GL0034 to the subject once a week for at least 4 weeks, or (b) The weight loss is at least -8 kg over a period of about 52 days following the administration of the following to the subject, or at least -6 kg over a period of about 78 days, wherein the administration is (i) a dose of the pharmaceutical composition containing 450 μg of GL0034 once a week for at least two weeks, (ii) a dose of the pharmaceutical composition containing 900 μg of GL0034 once a week for at least two weeks, and (iii) a dose of the pharmaceutical composition containing 1520 μg of GL0034 once a week for at least four weeks, according to claim 42.

55. The pharmaceutical composition according to claim 42, wherein the reduction in leptin levels from baseline is dose-dependent.

56. The pharmaceutical composition according to claim 42, wherein the change in leptin level from baseline is at least -7 ng / mL over a period of about 8 days after administration of a dose of the pharmaceutical composition containing 1520 μg of GL0034 to the subject, or at least -11 ng / mL over a period of about 8 days after administration of a dose of the pharmaceutical composition containing 2000 μg of GL0034 to the subject, or at least -12 ng / mL over a period of about 8 days after administration of a dose of the pharmaceutical composition containing 2520 μg of GL0034 to the subject.

57. The pharmaceutical composition according to claim 42, wherein the reduction in TG levels from baseline is observed on day 8 and persists for at least 51 days or at least 78 days after administration of the pharmaceutical composition to the subject.

58. (a) The change in TG level from baseline is at least -1 mmol / L over a period of about 8 days after administration of a dose of the pharmaceutical composition containing 2000 μg of GL0034 to the subject, or at least -1 mmol / L over a period of about 22 days after administration of a dose of the pharmaceutical composition containing 2520 μg of GL0034 to the subject, or (b) The change in TG level is at least -21 mg / dL for a period of about 51 days after the following administration to the subject, or at least -11 mg / dL for a period of about 78 days, wherein the administration is (i) a dose of the pharmaceutical composition containing 450 μg of GL0034 once a week for at least two weeks, (ii) a dose of the pharmaceutical composition containing 900 μg of GL0034 once a week for at least two weeks, and (iii) a dose of the pharmaceutical composition containing 1520 μg of GL0034 once a week for at least four weeks, according to claim 42.

59. The pharmaceutical composition according to claim 42, wherein the reduction in TC level from baseline is at least -29 mg / dL over a period of about 51 days following the administration to the subject, or at least -6 mg / dL over a period of about 78 days, the administration being (i) a dose of the pharmaceutical composition containing 450 μg of GL0034 once a week for at least two weeks, (ii) a dose of the pharmaceutical composition containing 900 μg of GL0034 once a week for at least two weeks, and (iii) a dose of the pharmaceutical composition containing 1520 μg of GL0034 once a week for at least four weeks.

60. The pharmaceutical composition according to claim 42, wherein the change in LDL level from baseline is at least -24 mg / dL over a period of about 51 days after the following administration to the subject, or at least -20 mg / dL over a period of about 78 days, the administration being (i) a dose of the pharmaceutical composition containing 450 μg of GL0034 once a week for at least two weeks, (ii) a dose of the pharmaceutical composition containing 900 μg of GL0034 once a week for at least two weeks, and (iii) a dose of the pharmaceutical composition containing 1520 μg of GL0034 once a week for at least four weeks.

61. The pharmaceutical composition according to claim 42, wherein the increase in HDL levels from baseline is at least 3 mg / dL over a period of about 78 days following the administration to the subject, the administration being (i) a dose of the pharmaceutical composition containing 450 μg of GL0034 once a week for at least two weeks, (ii) a dose of the pharmaceutical composition containing 900 μg of GL0034 once a week for at least two weeks, and (iii) a dose of the pharmaceutical composition containing 1520 μg of GL0034 once a week for at least four weeks.

62. The pharmaceutical composition according to claim 42, wherein the clinically significant change from baseline in the subject is a decrease in blood pressure.

63. The pharmaceutical composition according to claim 62, wherein the reduction in blood pressure is a reduction in systolic blood pressure.

64. The pharmaceutical composition according to claim 62, wherein the reduction in blood pressure is a reduction in diastolic blood pressure.

65. The pharmaceutical composition according to claim 63, wherein the reduction in systolic blood pressure from baseline is at least about 18 mmHg or at least about 14% over a period of about 23 days after administration to the subject of a dose of the pharmaceutical composition containing 450 μg of GL0034 once a week for at least four weeks.

66. The pharmaceutical composition according to claim 64, wherein the reduction in diastolic blood pressure from baseline is at least about 12 mmHg or at least about 14% over a period of about 23 days after administration to the subject of a dose of the pharmaceutical composition containing at least 450 μg of GL0034 once a week for at least 4 weeks.

67. The pharmaceutical composition according to claim 62, wherein the reduction in blood pressure in the subject is greater than the reduction in blood pressure after administration of (a) 1.7 to 2.4 mg of semaglutide once a week, or (b) 5 to 15 mg of tilzepatide once a week.

68. The pharmaceutical composition according to any one of claims 1 to 67, wherein administration of the pharmaceutical composition to the subject results in a time-dependent decrease in the frequency of adverse events (AEs) in the subject.

69. The pharmaceutical composition according to claim 68, wherein the AE is one or more of nausea, vomiting, and / or loss of appetite.

70. The pharmaceutical composition according to claim 68, wherein the reduction in the frequency of AE is dose-dependent.

71. The pharmaceutical composition according to any one of claims 1 to 12, wherein administration of a higher dose of the pharmaceutical composition to the subject does not result in an increase in severe adverse events (TEAEs) that occur under severe treatment.

72. A pharmaceutical composition comprising GL0034 for the treatment of hypertension in a subject, wherein a therapeutically effective dose of the pharmaceutical composition is administered to the subject.

73. The pharmaceutical composition according to claim 72, wherein the subject is obese.

74. The pharmaceutical composition according to claim 73, wherein the subject is not diabetes.

75. The subject is the pharmaceutical composition according to claim 72, which has metabolic disorders.

76. The pharmaceutical composition according to claim 75, wherein the metabolic disorder is metabolic dysfunction-related fatty liver disease (MASLD).

77. The pharmaceutical composition according to claim 76, wherein the MASLD is metabolic dysfunction-associated steatohepatitis (MASH).

78. The pharmaceutical composition according to claim 75, wherein the metabolic disorder is diabetes mellitus or hypertriglyceridemia.

79. The pharmaceutical composition according to claim 78, wherein the metabolic disorder is type 2 diabetes.

80. The pharmaceutical composition according to any one of claims 72 to 79, which is administered subcutaneously to the subject.

81. The pharmaceutical composition according to claim 80, wherein the pharmaceutical composition is administered to the subject by subcutaneous injection.

82. The pharmaceutical composition according to claim 81, wherein the pharmaceutical composition is administered to the subject using an auto-injector or a pre-filled syringe.

83. The pharmaceutical composition according to any one of claims 72 to 82, wherein a dose of the pharmaceutical composition containing 450 μg of GL0034 is administered to the subject.

84. The pharmaceutical composition according to claim 83, wherein administration of the pharmaceutical composition results in a reduction of systolic blood pressure from baseline in the subject by at least about 18 mmHg or at least about 14% over a period of about 23 days after administration of the pharmaceutical composition.

85. The pharmaceutical composition according to claim 83, wherein administration of the pharmaceutical composition results in a reduction of diastolic blood pressure from baseline in the subject by at least about 12 mmHg or at least about 14% over a period of about 23 days after administration of the pharmaceutical composition.

86. The pharmaceutical composition according to any one of claims 72 to 85, wherein the reduction in blood pressure in the subject is greater than the reduction in blood pressure after administration of (a) 1.7 to 2.4 mg of semaglutide or (b) 5 to 15 mg of tilzepatide once a week.

87. A method for treating obesity in a subject, comprising administering a therapeutically effective amount of GL0034 to the subject.

88. The method according to claim 87, wherein the subject is not diabetes.

89. The aforementioned subjects have a body mass index (BMI) of at least 28 kg / m². ２ It is either ≥ 27 kg / m ２ The method according to either claim 87 or claim 88, wherein the patient has at least one weight-related comorbidity.

90. A method for treating a metabolic disorder in a subject, comprising administering a therapeutically effective amount of GL0034 to the subject.

91. The method according to claim 90, wherein the metabolic disorder is metabolic dysfunction-related fatty liver disease (MASLD).

92. The method according to claim 91, wherein the MASLD is metabolic dysfunction-associated steatohepatitis (MASH).

93. The method according to claim 90, wherein the metabolic disorder is diabetes mellitus or hypertriglyceridemia.

94. The method according to claim 93, wherein the metabolic disorder is type 2 diabetes.

95. The method according to any one of claims 87 to 94, wherein the subject has hypertension.

96. GL0034 is administered subcutaneously to the subject according to any one of claims 87 to 95.

97. The method according to claim 96, wherein GL0034 is administered to the subject by subcutaneous injection.

98. The method according to claim 97, wherein GL0034 is administered to the subject using an auto-injector or a pre-filled syringe.

99. The method according to any one of claims 87 to 98, wherein a dose containing 200 μg to 8000 μg of GL0034 is administered to the subject.

100. The method according to claim 99, wherein the dose comprises 300 μg to 6000 μg of GL0034.

101. The method according to claim 100, wherein the dose comprises 400 μg to 4000 μg of GL0034.

102. The method according to claim 101, wherein the dose comprises 1,000 μg to 3,000 μg of GL0034.

103. The method according to any one of claims 87 to 102, wherein the dose of GL0034 is administered to the subject once a week or once every two weeks.

104. The administration of GL0034 to the subject results in an average maximum concentration (C) of GL0034 ranging from 75 ng / mL to 1200 ng / mL. ｍａｘ The method according to any one of claims 87 to 102, which brings about ).

105. The area under the concentration-time curve (AUC) of GL0034 administered to the subject over a 22-day period, where the concentration ranges from 6200 ng*h / mL to 406300 ng*h / mL. ０－ｔ The method according to any one of claims 87 to 102, which brings about ).

106. The method according to claim 102, wherein the dose comprises 1520 μg, 2000 μg, or 2520 μg of GL0034.

107. The administration of GL0034 to the subject results in an average maximum concentration (C) of GL0034 ranging from 227 ng / mL to 367 ng / mL. ｍａｘ The method according to claim 106, which brings about ).

108. The area under the concentration-time curve (AUC) of GL0034 administered to the subject over a 22-day period at concentrations ranging from 30313 ng*h / mL to 83082 ng*h / mL. ０－ｔ The method according to claim 106, which brings about ).

109. The administration of GL0034 to the subject is such that the plasma drug half-life of GL0034 is 90 to 120 hours (t １／２ The method according to any one of claims 87 to 107, which brings about ).

110. The administration of GL0034 to the subject is within 98 to 113 hours, which is the plasma drug half-life (t １／２ The method according to claim 107, which brings about ).

111. The method according to any one of claims 87 to 98, wherein GL0034 is administered to the subject once a week or once every two weeks.

112. The method according to any one of claims 87 to 98 or 111, wherein a dose containing 450 μg, 680 μg, 900 μg, 1520 μg, 2000 μg, or 2520 μg of GL0034 is administered to the subject.

113. The method according to claim 112, wherein the dose of GL0034 is administered to the subject once a week or once every two weeks.

114. GL0034 was administered to the subject at a dose of 450 μg once a week for at least four weeks, and the average peak concentration (C) of GL0034 was measured. ｍａｘ The method according to claim 112, wherein the amount is 101 ng / mL to 142 ng / mL.

115. The area under the concentration-time curve (AUC) of GL0034 administered to the subject was 12814 ng*h / mL to 18537 ng*h / mL over a period of 22 days. ０－ｔ The method according to claim 114, which brings about ).

116. The administration of GL0034 to the subject resulted in a plasma drug half-life (t) of GL0034 of 102 hours by day 22. １／２ The method according to claim 114, which brings about ).

117. GL0034 was administered to the subjects at a dose of 680 μg once a week for at least four weeks, and the average peak concentration (C) of GL0034 was measured. ｍａｘ The method according to claim 112, wherein the amount is 169 ng / mL to 267 ng / mL.

118. The area under the concentration-time curve (AUC) of GL0034 administered to the subject was 24576 ng*h / mL to 34537 ng*h / mL over a period of 22 days. ０－ｔ The method according to claim 117, which brings about ).

119. Administration of GL0034 to the subject resulted in a plasma drug half-life (t) of GL0034 of 122.9 ± 16.5 hours by day 22. １／２ The method according to claim 117, which brings about ).

120. The method according to any one of claims 87 to 98, wherein (i) GL0034 is administered to the subject once a week for at least two weeks at a dose of 50 μg to 200 μg, (ii) GL0034 is administered to the subject once a week for at least two weeks at a dose of 200 μg to 400 μg, (iii) GL0034 is administered to the subject once a week for at least two weeks at a dose of 500 μg to 700 μg, (iv) GL0034 is administered to the subject once a week for at least two weeks at a dose of 1200 μg to 1500 μg, and (v) GL0034 is administered to the subject once a week for at least four weeks at a dose of 2000 μg to 3000 μg.

121. (i) GL0034 is administered to the subject at a dose of 450 μg once a week for at least two weeks; (ii) GL0034 is administered to the subject at a dose of 900 μg once a week for at least two weeks; and (iii) GL0034 is administered to the subject at a dose of 1520 μg once a week for at least four weeks, according to any one of claims 87 to 98.

122. The administration of GL0034 to the subject resulted in an average maximum concentration (C) of GL0034 ranging from 112 ng / mL to 708 ng / mL. ｍａｘ The method according to claim 121, which brings about ).

123. The area under the concentration-time curve (AUC) of GL0034 administered to the subject over a 50-day period, where the concentration ranges from 12942 ng*h / mL to 76320 ng*h / mL. ０－ｔ The method according to claim 121, which brings about ).

124. Administration of GL0034 to the aforementioned subjects resulted in a plasma drug half-life (t) of GL0034 of 106.8 ± 33.7 hours by day 50. １／２ The method according to claim 121, which brings about ).

125. The method according to any one of claims 87 to 98, comprising: (i) administering an initial dose containing 200 μg to 680 μg of GL0034 to the subject for at least four weeks; (ii) administering an increasing dose containing 680 μg to 900 μg of GL0034 to the subject once a week for at least two weeks; and (iii) administering a maintenance dose containing 1500 μg to 2000 μg of GL0034 to the subject once a week for at least two weeks.

126. The method according to any one of claims 87 to 98, comprising: (i) administering an initial dose containing 450 μg to 680 μg of GL0034 to the subject for at least four weeks; and (ii) administering an increasing dose containing 680 μg to 900 μg of GL0034 to the subject once a week for at least two weeks.

127. The method according to any one of claims 87 to 98, comprising: (i) administering an initial dose containing 450 μg to 680 μg of GL0034 to the subject for at least four weeks; (ii) administering an increasing dose containing 680 μg to 900 μg of GL0034 to the subject once a week for at least two weeks; and (iii) administering a maintenance dose containing 1520 μg to 2000 μg of GL0034 to the subject once a week for at least two weeks.

128. Administration of GL0034 to the subjects resulted in one or more clinically significant changes from baseline, the clinically significant changes from baseline being a decrease in alanine transaminase (ALT) levels, a decrease in aspartate aminotransferase (AST) levels, a decrease in gamma-glutamyltransferase (GGT) levels, a decrease in fasting insulin levels, a decrease in fasting blood glucose levels, a decrease in glycated hemoglobin (%HbA1c), and an evaluation of the insulin resistance homeostasis model (HOMA-I). The method according to any one of claims 87 to 127, wherein the reduction is R), weight loss, leptin level decrease, triglyceride (TG) level decrease, total cholesterol (TC) level decrease, low-density lipoprotein (LDL) level decrease, high-density lipoprotein (HDL) level increase, TG / HDL ratio decrease, FGF-21 increase in liver, uncoupling protein-1 (UCP-1) level in brown adipose tissue (BAT) and / or white adipose tissue (WAT), and / or blood pressure decrease.

129. The method according to claim 128, wherein the reduction in ALT value from baseline persists for at least 23 days, at least 52 days, or at least 78 days after administration of GL0034 to the subject.

130. (a) The change in ALT value from baseline is at least -9 U / L over a period of approximately 23 days after administration of a dose containing 450 μg of GL0034 to the subject, or at least -3 U / L over a period of approximately 23 days after administration of a dose containing 680 μg of GL0034 to the subject, (b) The change in ALT value is at least -7 U / L for a period of about 51 days after the administration to the subject, or at least -1 U / L for a period of about 78 days, wherein the administration is (i) a dose containing 450 μg of GL0034 once a week for at least two weeks, (ii) a dose containing 900 μg of GL0034 once a week for at least two weeks, and (iii) a dose containing 1520 μg of GL0034 once a week for at least four weeks, according to claim 128.

131. The method according to claim 128, wherein the reduction in AST value from baseline persists for at least 23 days, at least 51 days, or at least 78 days after administration of GL0034 to the subject.

132. The method according to claim 128, wherein the change in AST value from baseline is at least -4 U / L over a period of about 51 days after the following administration to the subject, or at least -1 U / L over a period of about 78 days, the administration being (i) a dose containing 450 μg of GL0034 once a week for at least two weeks, (ii) a dose containing 900 μg of GL0034 once a week for at least two weeks, and (iii) a dose containing 1520 μg of GL0034 once a week for at least four weeks.

133. The method according to claim 128, wherein the reduction in GGT levels from baseline is sustained for at least 23 days, at least 51 days, or at least 78 days after administration of GL0034 to the subject.

134. The method according to claim 128, wherein the change in the GGT value from baseline is at least -3 U / L over a period of about 51 days after the following administration to the subject, or at least -1 U / L over a period of about 78 days, the administration being (i) a dose containing 450 μg of GL0034 once a week for at least two weeks, (ii) a dose containing 900 μg of GL0034 once a week for at least two weeks, and (iii) a dose containing 1520 μg of GL0034 once a week for at least four weeks.

135. The method according to claim 128, wherein the reduction in fasting insulin levels from baseline persists for at least 23 days or at least 51 days after administration of GL0034 to the subject.

136. The method according to claim 128, wherein the change in fasting insulin levels from baseline is at least -5 pmol / L for a period of about 23 days after administration to the subject of a dose containing 680 μg of GL0034 once weekly for at least 4 weeks, or at least -11 pmol / L for a period of about 51 days after the following administrations to the subject, the administrations being (i) a dose containing 450 μg of GL0034 once weekly for at least 2 weeks, (ii) a dose containing 900 μg of GL0034 once weekly for at least 2 weeks, and (iii) a dose containing 1520 μg of GL0034 once weekly for at least 4 weeks.

137. The method according to claim 128, wherein the reduction in fasting glucose persists for at least 23 days or at least 51 days after administration of GL0034 to the subject.

138. The method according to claim 128, wherein the fasting glucose reduction is at least -3 mg / dL for a period of about 23 days after administration to the subject of a dose containing 450 μg of GL0034 once a week for at least 4 weeks, or at least -5 mg / dL for a period of about 23 days after administration to the subject of a dose containing 680 μg of GL0034 once a week for at least 4 weeks, or at least -8 mg / dL for a period of about 51 days after the following administrations to the subject, wherein the administrations are (i) a dose containing 450 μg of GL0034 once a week for at least 2 weeks, (ii) a dose containing 900 μg of GL0034 once a week for at least 2 weeks, and (iii) a dose containing 1520 μg of GL0034 once a week for at least 4 weeks.

139. The method according to claim 128, wherein the weight loss is sustained for at least 8 days, at least 15 days, at least 22 days, at least 29 days, at least 50 days, at least 52 days, or at least 78 days after administration of GL0034 to the subject.

140. (a) The weight loss is at least -2 kg over a period of about 22 days after administration of a dose containing 2000 μg of GL0034 to the subject, or at least -2 kg over a period of about 22 days after administration of a dose containing 1520 μg of GL0034 to the subject, or at least -3 kg over a period of about 22 days after administration of a dose containing 2520 μg of GL0034 to the subject, or at least -3 kg over a period of about 29 days after administration of a dose containing 450 μg of GL0034 to the subject once a week for at least 4 weeks, or at least -4 kg over a period of about 29 days after administration of a dose containing 680 μg of GL0034 to the subject once a week for at least 4 weeks, or (b) The method according to claim 128, wherein the weight loss is at least -8 kg over a period of about 52 days following the administration of the following to the subject, or at least -6 kg over a period of about 78 days, the administration being (i) a dose containing 450 μg of GL0034 once a week for at least two weeks, (ii) a dose containing 900 μg of GL0034 once a week for at least two weeks, and (iii) a dose containing 1520 μg of GL0034 once a week for at least four weeks.

141. The method according to claim 128, wherein the reduction in leptin levels from baseline is dose-dependent.

142. The method according to claim 128, wherein the change in leptin level from baseline is at least -7 ng / mL over a period of about 8 days after administration of a dose containing 1520 μg of GL0034 to the subject, or at least -11 ng / mL over a period of about 8 days after administration of a dose containing 2000 μg of GL0034 to the subject, or at least -12 ng / mL over a period of about 8 days after administration of a dose containing 2520 μg of GL0034 to the subject.

143. The method according to claim 128, wherein the decrease in TG levels from baseline is observed on day 8 and persists for at least 51 days or at least 78 days after administration of GL0034 to the subject.

144. (a) The change in TG level from baseline is at least -1 mmol / L over a period of about 8 days after administration of a dose containing 2000 μg of GL0034 to the subject, or at least -1 mmol / L over a period of about 22 days after administration of a dose containing 2520 μg of GL0034, or (b) The change in TG level is at least -21 mg / dL for a period of about 51 days after the following administration to the subject, or at least -11 mg / dL for a period of about 78 days, wherein the administration is (i) a dose containing 450 μg of GL0034 once a week for at least two weeks, (ii) a dose containing 900 μg of GL0034 once a week for at least two weeks, and (iii) a dose containing 1520 μg of GL0034 once a week for at least four weeks, according to claim 128.

145. The method according to claim 128, wherein the reduction in TC level from baseline is at least -29 mg / dL over a period of about 51 days following the administration to the subject, or at least -6 mg / dL over a period of about 78 days, wherein the administration is (i) a dose containing 450 μg of GL0034 once a week for at least two weeks, (ii) a dose containing 900 μg of GL0034 once a week for at least two weeks, and (iii) a dose containing 1520 μg of GL0034 once a week for at least four weeks.

146. The method according to claim 128, wherein the change in LDL level from baseline is at least -24 mg / dL over a period of about 51 days after the following administration to the subject, or at least -20 mg / dL over a period of about 78 days, wherein the administration is (i) a dose containing 450 μg of GL0034 once a week for at least two weeks, (ii) a dose containing 900 μg of GL0034 once a week for at least two weeks, and (iii) a dose containing 1520 μg of GL0034 once a week for at least four weeks.

147. The method according to claim 128, wherein the increase in HDL levels from baseline is at least 3 mg / dL over a period of about 78 days following the administration to the subject, the administration being (i) a dose containing 450 μg of GL0034 once a week for at least two weeks, (ii) a dose containing 900 μg of GL0034 once a week for at least two weeks, and (iii) a dose containing 1520 μg of GL0034 once a week for at least four weeks.

148. The method according to claim 128, wherein the clinically significant change from baseline in the subject is a decrease in blood pressure.

149. The method according to claim 148, wherein the reduction in blood pressure is a reduction in systolic blood pressure.

150. The method according to claim 148, wherein the reduction in blood pressure is a reduction in diastolic blood pressure.

151. The method according to claim 149, wherein the reduction in systolic blood pressure from baseline is at least about 18 mmHg or at least about 14% over a period of about 23 days after administration to the subject of a dose containing 450 μg of GL0034 once a week for at least 4 weeks.

152. The method according to claim 150, wherein the reduction in diastolic blood pressure from baseline is at least about 12 mmHg or at least about 14% over a period of about 23 days after administration to the subject of a dose containing at least 450 μg of GL0034 once a week for at least 4 weeks.

153. The method according to claim 148, wherein the reduction in blood pressure in the subject is greater than the reduction in blood pressure after administration of (a) 1.7 to 2.4 mg of semaglutide once a week, or (b) 5 to 15 mg of tilzepatide once a week.

154. The method according to any one of claims 87 to 153, wherein administration of GL0034 to the subject results in a time-dependent decrease in the frequency of adverse events (AEs) in the subject.

155. The method according to claim 154, wherein the AE is one or more of nausea, vomiting, and / or loss of appetite.

156. The method according to claim 154, wherein the reduction in the frequency of AE is dose-dependent.

157. The method according to any one of claims 87 to 98, wherein administration of a higher dose of GL0034 to the subject does not result in an increase in severe adverse events (TEAEs) occurring under treatment.

158. A method for treating hypertension in a subject, comprising administering a therapeutically effective amount of GL0034 to the subject.

159. The method according to claim 158, wherein the subject is obese.

160. The method according to claim 159, wherein the subject is not diabetic.

161. The method according to claim 158, wherein the subject has a metabolic disorder.

162. The method according to claim 161, wherein the metabolic disorder is metabolic dysfunction-related fatty liver disease (MASLD).

163. The method according to claim 162, wherein the MASLD is metabolic dysfunction-associated steatohepatitis (MASH).

164. The method according to claim 161, wherein the metabolic disorder is diabetes mellitus or hypertriglyceridemia.

165. The method according to claim 164, wherein the metabolic disorder is type 2 diabetes.

166. GL0034 is administered subcutaneously to the subject according to any one of claims 158 to 165.

167. The method according to claim 166, wherein GL0034 is administered to the subject by subcutaneous injection.

168. The method according to claim 167, wherein GL0034 is administered to the subject using an auto-injector or a pre-filled syringe.

169. The method according to any one of claims 158 to 168, wherein a dose containing 450 μg of GL0034 is administered to the subject.

170. The method according to claim 169, wherein administration of GL0034 results in a reduction of systolic blood pressure from baseline in the subject, which is at least about 18 mmHg or at least about 14% over a period of about 23 days following administration of GL0034.

171. The method according to claim 169, wherein administration of GL0034 results in a reduction of diastolic blood pressure from baseline in the subject, which is at least about 12 mmHg or at least about 14% over a period of about 23 days following administration of GL0034.

172. The method according to any one of claims 158 to 171, wherein the reduction in blood pressure in the subject is greater than the reduction in blood pressure after administration of (a) 1.7 to 2.4 mg of semaglutide or (b) 5 to 15 mg of tilzepatide once a week.

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