Treatment method using mazdutide

Abstract

The present invention belongs to the field of medicine, and specifically relates to a treatment method using mazdutide. The present invention provides a method for preventing or treating obesity or overweight, and a method for improving body weight in a patient in need thereof, the method comprising administering to the patient in need thereof a prophylactically or therapeutically effective amount of a target compound in a dosing regimen consisting of at least three dosing cycles. The present invention also provides a target compound for preventing or treating obesity or overweight in a patient in need thereof, wherein in at least three dosing cycles, a prophylactically or therapeutically effective amount of the above target compound is administered to the patient in need thereof. The dosing regimen of mazdutide provided by the present invention has a very significant weight loss effect, and a significant weight loss effect can be achieved at a relatively low dose within a relatively short time, and at the same time, the blood pressure, blood lipids, and serum uric acid levels of the subject can be improved.

Description

Technical Field

[0001] Cross - reference to related applications This invention claims the priority of the invention patent application with the application number 202210622648.7 and the invention title "Therapeutic method using mazdutide", which was filed with the China National Intellectual Property Administration on June 1, 2022, and the entire content thereof is incorporated herein by reference.

[0002] Technical Field This invention belongs to the field of medicine, and specifically relates to a therapeutic method using mazdutide.

Background Art

[0003] The most preferred basic treatment measure for overweight or obese individuals is lifestyle intervention. However, there are still quite a number of patients who cannot lose weight or achieve the desired weight loss goal for various reasons. For such patients, it is conceivable to use drugs to assist in weight loss. According to Chinese guidelines, for patients with a BMI ≥ 28 kg / m 2 and still cannot achieve a 5% weight loss after 3 months of lifestyle intervention, or for patients with a BMI ≥ 24 kg / m 2 who have one of the obesity - related complications such as hyperglycemia, hypertension, dyslipidemia, non - alcoholic fatty liver disease (NAFLD), pain in weight - bearing joints, sleep apnea syndrome, etc., based on lifestyle and behavioral interventions, the use of drug - induced weight loss treatment is recommended.

[0004] Currently, long-term (≥12 weeks) obesity treatment drugs approved by the FDA mainly include phentermine and topiramate extended-release capsules, bupropion hydrochloride-naltrexone hydrochloride, liraglutide, and semaglutide injection solutions. And short-term weight loss drugs (<12 weeks) include diethylpropion, phendimetrazine, phentermine, benzphetamine, etc. Early marketed diet drugs have a certain weight loss effect, but side effects are also similarly notable, and their use is restricted. For example, diethylpropion may cause tachycardia and insomnia, phentermine may cause insomnia, dry mouth, and constipation, the combination preparation of phentermine and fenfluramine may cause primary pulmonary arterial hypertension and heart valve insufficiency (however, no obvious correlation is seen when using phentermine alone), and orlistat may cause fat-soluble vitamin deficiency, gastrointestinal fullness, urgency of defecation, steatorrhea, etc. Currently, multiple types of GLP-1 single receptor agonists, such as liraglutide, etc., are on the market. Taking semaglutide, which is currently the weight loss drug with the best therapeutic effect globally on the market, as an example, continuous administration for 12 weeks results in a weight loss of about 6%, and continuous administration for 1 year results in a weight loss of about 13% - 16%. However, for obese individuals with a relatively high BMI, such as those with a BMI > 30 kg / m 2 ², because their weight loss needs are higher, although GLP-1 single receptor agonists have shown a certain weight loss treatment effect, there are still huge unmet medical needs in the field of obesity treatment.

[0005] In recent years, multi-receptor agonists targeting multiple metabolic pathways have become the focus of drug development in the field of metabolic diseases. As is evident from the results of multiple preclinical and clinical studies, co-administration of GLP-1 receptor agonists and other incretins shows a promoting or synergistic effect. Compared with the single use or combination of single-target agonists, single-molecule multi-receptor agonists with balanced activity at multiple receptors are expected to further improve in terms of maximizing therapeutic effects, reducing side effects, and pharmacokinetics. Therefore, GLP-1-based single-molecule multi-receptor agonists have advantages such as synergistic effects, improved tolerance, and enhanced safety.

[0006] Mazdutide is a long-acting synthetic peptide similar to mammalian oxyntomodulin (OXM). OXM is a peptide hormone secreted by human intestinal L cells after nutrient intake and is a dual agonist of the glucagon-like peptide-1 receptor (GLP-1R) and the glucagon receptor (GCGR). Dual agonists of GLP-1R and GCGR combine the pyrogenic and lipolytic effects of glucagon with the delayed gastric emptying effect of GLP-1 to produce a significant weight loss effect, and buffer the blood glucose-raising effect of glucagon by the insulin secretion-promoting effect of GLP-1, thereby effectively controlling blood glucose. Injecting OXM in the body significantly reduces body weight and appetite and increases energy consumption. As an OXM analog, mazdutide functions by simultaneously activating GLP-1R and GCGR.

Summary of the Invention

Problems to be Solved by the Invention

[0007] The present invention aims to provide a mazdutide administration plan that fully exerts the therapeutic effect of mazdutide on obesity or overweight by utilizing appropriate dosages and appropriate times.

Means for Solving the Problems

[0008] [1] A method for preventing or treating obesity or overweight, comprising administering a prophylactically or therapeutically effective amount of a target compound to a patient in need thereof in a dosing schedule consisting of at least three dosing cycles, wherein said at least three dosing cycles include the following: (i) A first dosing cycle in which about one unit dose of said target compound is administered weekly for at least 3 weeks, (ii) A second dosing cycle in which about two unit doses of said target compound are administered weekly for at least 3 weeks, (iii) A third dosing cycle in which about three unit doses of said target compound are administered weekly for at least 3 weeks, and optionally, (iv) A fourth dosing cycle in which about four unit doses of said target compound are administered weekly for at least 3 weeks, wherein said unit dose is 2.2 mg to 3.5 mg, and said target compound is selected from mazdutide or a pharmaceutically acceptable salt thereof.

[0009] [2] By the method according to [1], wherein in said dosing schedule, the last dosing cycle is at least 3 weeks, preferably at least 4 weeks, and the duration of each of the remaining said dosing cycles is independently of each other 3 weeks to 5 weeks, preferably about 4 weeks, Optionally, the third dosing cycle is the last dosing cycle in said dosing schedule, and the duration of the third dosing cycle is at least 3 weeks, preferably at least 4 weeks, Or, the fourth dosing cycle is the last dosing cycle in said dosing schedule, and the duration of the fourth dosing cycle is at least 3 weeks, preferably at least 4 weeks.

[0010] [3] By the method according to [1] or [2], wherein said target compound is administered to said patient once or multiple times per week in each of said dosing cycles, Preferably, said target compound is administered to said patient once per week in each of said dosing cycles.

[0011] [4] By the method according to any one of [1] to [3], wherein the unit dose is 2.2 mg to 3 mg, 2.2 mg to 2.8 mg, 2.4 mg to 2.6 mg, 2.5 mg to 3.5 mg, 2.7 mg to 3.3 mg, 2.9 mg to 3.1 mg, Optionally, the unit dose is about 2.2 mg, about 2.3 mg, about 2.4 mg, about 2.5 mg, about 2.6 mg, about 2.7 mg, about 2.8 mg, about 2.9 mg, about 3.0 mg, about 3.1 mg, about 3.2 mg, about 3.3 mg, about 3.4 mg, or about 3.5 mg.

[0012] [5] By the method according to any one of [1] to [4], wherein the method includes the step of administering the target compound in the following dosing schedule I: In the first dosing cycle, administer 2.2 mg to 3 mg of the target compound to the patient weekly for 3 to 5 weeks, Next, in the second dosing cycle, administer 4.5 mg to 5.5 mg of the target compound to the patient weekly for 3 to 5 weeks, Next, in the third dosing cycle, administer 7 mg to 8 mg of the target compound to the patient weekly for 3 to 5 weeks, Next, in the fourth dosing cycle, administer 9.5 mg to 10.5 mg of the target compound to the patient weekly for at least 3 weeks, Optionally, in the first dosing cycle, administer 2.2 mg to 2.8 mg of the target compound to the patient weekly for about 4 weeks, preferably administer about 2.5 mg of the target compound to the patient weekly for about 4 weeks, more preferably administer about 2.5 mg of the target compound to the patient once a week for about 4 weeks, Optionally, in the second dosing cycle, administer 4.7 mg to 5.3 mg of the target compound to the patient weekly for about 4 weeks, preferably administer about 5 mg of the target compound to the patient weekly for about 4 weeks, more preferably administer about 5 mg of the target compound to the patient once a week for about 4 weeks, Optionally, in the third dosing cycle, the target compound is administered to the patient at a dose of 7.2 mg to 7.8 mg per week for about 4 weeks, preferably at a dose of about 7.5 mg of the target compound per week to the patient for about 4 weeks, more preferably once a week, the target compound is administered to the patient at about 7.5 mg for about 4 weeks, Optionally, in the fourth dosing cycle, the target compound is administered to the patient at a dose of 9.7 mg to 10.3 mg per week for at least about 4 weeks, preferably at a dose of about 10 mg of the target compound per week to the patient for at least about 4 weeks, more preferably once a week, the target compound is administered to the patient at about 10 mg for at least 4 weeks.

[0013] [6] A method according to any one of [1] to [4], wherein, the method comprises the step of administering the target compound in dosing schedule II shown below: In the first dosing cycle, the target compound is administered to the patient at a dose of 2.5 mg to 3.5 mg per week for 3 to 5 weeks, Next, in the second dosing cycle, the target compound is administered to the patient at a dose of 5.5 mg to 6.5 mg per week for 3 to 5 weeks, Next, in the third dosing cycle, the target compound is administered to the patient at a dose of 8.5 mg to 9.5 mg per week for at least 3 weeks, Optionally, in the first dosing cycle, the target compound is administered to the patient at a dose of 2.7 mg to 3.3 mg per week for about 4 weeks, preferably at a dose of about 3 mg of the target compound per week to the patient for about 4 weeks, more preferably once a week, the target compound is administered to the patient at about 3 mg for about 4 weeks, Optionally, in the second dosing cycle, the target compound is administered to the patient at a dose of 5.7 mg to 6.3 mg per week for about 4 weeks, preferably at a dose of about 6 mg of the target compound per week to the patient for about 4 weeks, more preferably once a week, the target compound is administered to the patient at about 6 mg for about 4 weeks, Optionally, in the third dosing cycle, the target compound is administered to the patient at 8.7 mg to 9.3 mg per week for at least about 4 weeks, preferably, the target compound is administered to the patient at about 9 mg per week for at least about 4 weeks, more preferably, the target compound is administered to the patient at about 9 mg once a week for at least 4 weeks. Optionally, in the third dosing cycle, the target compound is administered to the patient at 8.7 mg to 9.3 mg per week for at least 16 weeks, preferably, the target compound is administered to the patient at about 9 mg per week for at least 16 weeks, more preferably, the target compound is administered to the patient at about 9 mg once a week for at least 16 weeks. Optionally, in the third dosing cycle, the target compound is administered to the patient at 8.7 mg to 9.3 mg per week for at least 40 weeks, preferably, the target compound is administered to the patient at about 9 mg per week for at least 40 weeks, more preferably, the target compound is administered to the patient at about 9 mg once a week for at least 40 weeks.

[0014] [7] By the method according to any one of [1] to [6], wherein the administration is by injection, preferably by subcutaneous injection.

[0015] [8] A method for improving body weight in a patient in need thereof, the method comprising administering to the patient a prophylactically or therapeutically effective amount of a target compound in a dosing schedule consisting of at least three dosing cycles, wherein the at least three dosing cycles include: (i) A first dosing cycle in which about one unit dose of the target compound is administered weekly for at least 3 weeks. (ii) A second dosing cycle in which about two unit doses of the target compound are administered weekly for at least 3 weeks. (iii) A third dosing cycle in which about three unit doses of the target compound are administered weekly for at least 3 weeks, and optionally, (iv) A fourth dosing cycle in which about four unit doses of the target compound are administered weekly for at least 3 weeks. Here, the above unit dose is 2.2 mg to 3.5 mg, and the above target compound is selected from mazdutide or a pharmaceutically acceptable salt thereof. Preferably, the prophylactically or therapeutically effective amount of the above target compound is administered to the above patient using the method described in any one of [1] to [7].

[0016] [9] A target compound for preventing or treating obesity or overweight in a patient in need thereof, wherein, in a dosing regimen consisting of at least three dosing cycles, a prophylactically or therapeutically effective amount of the above target compound is administered to the patient in need thereof, and the at least three dosing cycles include the following: (i) A first dosing cycle in which about one unit dose of the above target compound is administered weekly for at least 3 weeks. (ii) A second dosing cycle in which about two unit doses of the above target compound are administered weekly for at least 3 weeks. (iii) A third dosing cycle in which about three unit doses of the above target compound are administered weekly for at least 3 weeks, and optionally, (iv) A fourth dosing cycle in which about four unit doses of the above target compound are administered weekly for at least 3 weeks. Here, the above unit dose is 2.2 mg to 3.5 mg, and the above target compound is selected from mazdutide or a pharmaceutically acceptable salt thereof. Preferably, the prophylactically or therapeutically effective amount of the above target compound is administered to the above patient using the method described in any one of [1] to [7]. [Advantages of the Invention]

[0017] In some embodiments, the method for preventing or treating obesity or overweight provided by the present invention can achieve an obvious weight loss effect by administering mazdutide or a pharmaceutically acceptable salt thereof according to a specific dosing regimen, and at the same time can improve the subject's blood pressure, blood lipids, and serum uric acid levels.

[0018] In some specific embodiments, the present invention administers mazdutide or a pharmaceutically acceptable salt thereof to a patient in need according to dosing schedule I or dosing schedule II having different dosages. The present invention can show a significant therapeutic effect on weight loss for both dosing schedule I or dosing schedule II with different dosages of mazdutide, and has good overall tolerance and safety during the administration process of the patient, and is found to have high safety in clinical administration.

[0019] In some preferred embodiments, the present invention administers mazdutide or a pharmaceutically acceptable salt thereof to a patient in need according to dosing schedule II. Compared with dosing schedule I, dosing schedule II has a better weight loss effect. At the same time, the present invention unexpectedly finds that, compared with dosing schedule I, the duration of mazdutide in dosing schedule II is shorter and the dosage is also lower, but the weight loss rate of its subjects is higher. Therefore, dosing schedule II provided by the present invention does not bring a better therapeutic effect on weight loss by increasing the dosage and time, but achieves an optimal therapeutic effect on weight loss with relatively low dosage and relatively short time through a specific dosing schedule, and has the prospect of important clinical use.

[0020] In addition, compared with the dosing schedule for administering other similar drugs, dosing schedule II provided by the present invention also has a more significant weight loss effect.

[0021] At the same time, the present invention can obtain a better therapeutic effect on weight loss by extending the administration time of the maintenance dose in dosing schedule II, and in the extended administration process, the overall tolerance and safety of the patient are still good, and it has high safety in clinical administration.

Brief Description of the Drawings

[0022]

Figure 1

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Figure 6

Mode for Carrying Out the Invention

[0023] Hereinafter, embodiments of the present invention will be described, but the present invention is not limited thereto.

[0024] In the present invention, the terms "a", "an", or "the" may refer to "one", or may also refer to "one or more", "at least one", and "one or more".

[0025] In the present invention, the terms "comprising", "having", "including", or "containing" may refer to being inclusive or open - ended, and do not exclude additional, unrecited components or method steps. At the same time, "comprising", "having", "including", or "containing" may also indicate being closed, excluding additional, unrecited components or method steps.

[0026] In the present invention, when the expression "may" is used, it includes the meanings of both performing a certain process and not performing a certain process.

[0027] In the present invention, "optionally" or "at will" means that the events or circumstances described below may or may not occur, and the description includes both the case where the event occurs and the case where the event does not occur.

[0028] In the present invention, the numerical range indicated by using "at least numerical value A", "at most numerical value A", "numerical value A to numerical value B" or "numerical value A - numerical value B" refers to a range including the end point numerical values A and B.

[0029] In the present invention, "about" is used to define approximate numerical values for all numerical ranges and parameters of the present invention, where specific relevant numerical values are indicated as accurately as possible. Unless otherwise specified, it should be understood that all ranges, amounts, numerical values and percentages used in the present invention are all modified by "about". Here, "about" generally means that the actual numerical value is within ±10%, ±5%, ±1% or ±0.5% of a specific numerical value or range.

[0030] In the present invention, the terms "polypeptide", "peptide" and "protein" are used interchangeably herein and are polymers of amino acids of any length. The polymer may be linear or branched, may contain modified amino acids, and may be interrupted by non-amino acids. The term further includes amino acid polymers that have already been modified (such as any other operations such as disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation or complexation with a labeling component).

[0031] In the present invention, "unit dose" refers to the initial drug dose administered to a patient in each dosing schedule, which is usually smaller than the maximum effective dose required by the patient.

[0032] In the present invention, "maintenance dose" refers to the highest drug dose administered to a patient in each dosing schedule, that is, the maximum drug dose required by the patient, and the maintenance dose can be continuously administered over a period of time exceeding 3 weeks.

[0033] In the present invention, "treatment" includes delaying or weakening the progression of a disease or disorder, and includes reducing, alleviating or decreasing one or more symptoms of the disorder or medical condition, and does not necessarily mean completely suppressing the symptoms of the disease. In some embodiments, "treating obesity or overweight" as described in the present invention includes delaying weight gain, reducing weight, improving blood pressure, improving blood lipids, improving serum uric acid levels, and the like. In some embodiments, the improvement of blood pressure described in the present invention includes, but is not limited to, lowering diastolic blood pressure and systolic blood pressure. In some embodiments, the improvement of blood lipids described in the present invention includes, but is not limited to, a decrease in the content of low-density lipoprotein cholesterol, a decrease in the content of triglycerides, and / or a decrease in the total cholesterol content. In some embodiments, the improvement of serum uric acid level described in the present invention includes, but is not limited to, a decrease in the serum uric acid content.

[0034] In the present invention, the term "prevention" refers to reducing the symptoms after suffering from a disease as compared with the case of not contacting (for example, administering) a compound of the present invention or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of the present invention to a subject before suffering from the disease, and does not necessarily mean completely suppressing the disease.

[0035] In the present invention, the term "improvement of body weight" refers to a decrease in the body weight of a subject.

[0036] In the present invention, "obesity" refers to BMI ≧ 28.0 kg / m 2 and indicates.

[0037] In the present invention, "overweight" refers to 24 kg / m 2 ≦ BMI < 28.0 kg / m 2refers to and is accompanied by at least one of the following expressions: i. having strong appetite, experiencing hunger that cannot be endured before meals, and having a relatively large food intake per meal; ii. having one or more of prediabetes (impaired fasting glucose and / or impaired glucose tolerance), hypertension, dyslipidemia, fatty liver (within 6 months before screening); iii. having pain in the joints that support body weight; iv. having dyspnea due to obesity or obstructive sleep apnea syndrome.

[0038] In the present invention, the term "preventive or therapeutic effective amount" refers to an amount that effectively achieves a desired preventive or therapeutic result at a required dosage over a required period.

[0039] The compounds of the present invention may also be provided in the form of salts. These salts may be formed using conventional methods.

[0040] In the present invention, the term "pharmaceutically acceptable salt" refers to salts prepared from acids or bases that are relatively non-toxic to the target compound. When the target compound contains a relatively acidic functional group (e.g., a carboxyl group or a sulfonic acid group), a base addition salt can be obtained by contacting the free form with a sufficient amount of base in a pure solution or a suitable inert solvent. Non-limiting examples of pharmaceutically acceptable base addition salts include, but are not limited to, sodium salts, potassium salts, ammonium salts, calcium salts, magnesium salts, organic amine salts, or similar salts. When the compounds of the present disclosure contain a relatively basic functional group (e.g., an amino group or a guanidino group), an acid addition salt can be obtained by contacting the free form with a sufficient amount of acid in a pure solution or a suitable inert solvent. Non-limiting examples of pharmaceutically acceptable acid addition salts include inorganic acid salts (e.g., hydrochloride, hydrobromide, hydroiodide, nitrate, carbonate, bicarbonate, phosphate, monohydrogen phosphate, dihydrogen phosphate, phosphite, sulfate, bisulfate, etc.), organic acid salts (e.g., acetate, propionate, isobutyrate, malonate, succinate, suberate, maleate, fumarate, citrate, tartrate, lactate, mandelate, benzoate, phthalate, mesylate, besylate, p-toluenesulfonate, glucuronic acid, etc.), and amino acid salts (e.g., arginine salt, etc.), but are not limited thereto. Specific forms of pharmaceutically acceptable salts may also be referred to Berge et al., "Pharmaceutical Salts", Journal of Pharmaceutical Science, 1977, 66: 1-19).

[0041] In the present invention, "administration" refers to administration by a nurse, healthcare provider, patient, or any other individual, including self-administration. The above administration includes not only delivery to the body but also prescription, dispensing, or assisted delivery in any manner.

[0042] In the present invention, "individual", "patient" or "subject" includes mammals. Mammals include, but are not limited to, domestic animals (such as cows, goats, cats, dogs and horses), primates (such as non-human primates such as humans and monkeys), rabbits, and rodents (such as mice and rats). In some embodiments, the patients described in the present invention include obese and / or overweight individuals.

[0043] Mazdutide or a pharmaceutically acceptable salt thereof Mazdutide described in the present invention is a dual agonist of glucagon-like peptide-1 (GLP-1) and glucagon receptor (GCGR), and can bind to and activate GLP-1R and GCGR. Mazdutide may refer to the content shown in Patent CN201680036771.3, and the entire content of the above patent is incorporated herein by reference.

[0044] Mazdutide has the sequence shown in SEQ ID NO: 1: His-Xaa-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Lys-Tyr-Leu-Asp-Glu-Lys-Lys-Ala-Lys-Glu-Phe-Val-Glu-Trp-Leu-Leu-Glu-Gly-Gly-Pro-Ser-Ser-Gly, wherein Xaa is Aib, and the Lys at position 20 is ([2-(2-amino-ethoxy)-ethoxy]-acetyl) 2 -(γGlu) 1 -CO-(CH 2 ) 18 -CO 2 chemically modified by complexing with the ε-amino group of the side chain using H, and the carboxyl group of the C-terminal Gly is amidated to a C-terminal primary amide.

[0045] The chemical formula of Mazdutide is as follows:

Chemical formula

[0046] Mazdutide of the present invention can react with any number of inorganic acids and organic acids, thereby forming pharmaceutically acceptable acid addition salts. Pharmaceutically acceptable salts and conventional methods for preparing them are known in the art. See, for example, P. Stahl et al., Handbook of Pharmaceutical Salts: Properties, Selection and Use, 2nd Revised Edition (Wiley-VCH, 2011). Pharmaceutically acceptable salts of mazdutide of the present invention include trifluoroacetate, hydrochloride, and acetate.

[0047] Medical use and dosing schedule Mazdutide or a pharmaceutically acceptable salt thereof described in the present invention can be used for preventing or treating obesity or overweight. Further, by administering mazdutide or a pharmaceutically acceptable salt thereof according to a specific dosing schedule, it is possible to effectively reduce body weight, improve blood pressure, improve blood lipids, improve serum uric acid levels, etc. in obese or overweight patients.

[0048] <First Aspect> The present invention provides a method for preventing or treating obesity or overweight, the method comprising administering a prophylactically or therapeutically effective amount of a target compound to a patient in need thereof in a dosing schedule consisting of at least three dosing cycles, wherein the at least three dosing cycles include the following: (i) A first dosing cycle in which about 1 unit dose of the target compound is administered weekly for at least 3 weeks. (ii) A second dosing cycle in which about 2 unit doses of the target compound are administered weekly for at least 3 weeks. (iii) A third dosing cycle in which about 3 unit doses of the target compound are administered weekly for at least 3 weeks, and optionally, (iv) A fourth dosing cycle in which about 4 unit doses of the target compound are administered weekly for at least 3 weeks. Here, the above unit dose is 2.2 mg to 3.5 mg, and the above target compound is selected from mazdutide or a pharmaceutically acceptable salt thereof.

[0049] In some embodiments, the method for preventing or treating obesity or overweight described in the present invention comprises administering a prophylactically or therapeutically effective amount of a target compound to a patient in need thereof in a dosing schedule consisting of three dosing cycles, wherein the three dosing cycles include the following: (i) A first dosing cycle in which about 1 unit dose of the above target compound is administered weekly for at least 3 weeks. (ii) A second dosing cycle in which about 2 unit doses of the above target compound are administered weekly for at least 3 weeks. (iii) A third dosing cycle in which about 3 unit doses of the above target compound are administered weekly for at least 3 weeks. Here, the above unit dose is 2.2 mg to 3.5 mg, and the above target compound is selected from mazdutide or a pharmaceutically acceptable salt thereof.

[0050] In some other embodiments, the method for preventing or treating obesity or overweight described in the present invention comprises administering a prophylactically or therapeutically effective amount of a target compound to a patient in need thereof in a dosing schedule consisting of four dosing cycles, wherein the four dosing cycles include the following: (i) A first dosing cycle in which about 1 unit dose of the above target compound is administered weekly for at least 3 weeks. (ii) A second dosing cycle in which about 2 unit doses of the above target compound are administered weekly for at least 3 weeks. (iii) A third dosing cycle in which about 3 unit doses of the above target compound are administered weekly for at least 3 weeks. (iv) A fourth dosing cycle in which about 4 unit doses of the above target compound are administered weekly for at least 3 weeks. Here, the above unit dose is 2.2 mg to 3.5 mg, and the above target compound is selected from mazdutide or a pharmaceutically acceptable salt thereof.

[0051] (Duration of dosing cycle) Each dosing cycle described in the present invention causes a difference in the duration of each dosing cycle due to the order of time and the difference in the maximum drug dose required by the patient.

[0052] In some embodiments, the duration of each dosing cycle described in the present invention is at least 3 weeks, independently of each other.

[0053] Furthermore, in some embodiments, in the dosing schedule described in the present invention, the last dosing cycle is at least 3 weeks, preferably at least 4 weeks, and the duration of each of the remaining dosing cycles is, independently of each other, 3 to 5 weeks, preferably 4 weeks.

[0054] In the present invention, when the third dosing cycle is the last dosing cycle of the dosing schedule, the duration of the third dosing cycle is at least 3 weeks, preferably at least 4 weeks. Exemplarily, the duration of the third dosing cycle is at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 9 weeks, at least 10 weeks, at least 11 weeks, at least 12 weeks, at least 13 weeks, at least 14 weeks, at least 15 weeks, at least 16 weeks, at least 20 weeks, at least 30 weeks, at least 40 weeks, etc. The present invention does not cover the duration of the third dosing cycle as the last dosing cycle, and the duration of the third dosing cycle can be maintained until the time when the required preventive or therapeutic result is achieved, or until the end of the treatment determined by a physician or other healthcare provider.

[0055] In the present invention, when the fourth dosing cycle is the last dosing cycle of the dosing schedule, the duration of the fourth dosing cycle is at least 3 weeks, preferably at least 4 weeks. Exemplarily, the duration of the fourth dosing cycle is at least 3 weeks, at least 4 weeks, at least 5 weeks, at least 6 weeks, at least 7 weeks, at least 8 weeks, at least 9 weeks, at least 10 weeks, at least 11 weeks, at least 12 weeks, at least 13 weeks, at least 14 weeks, at least 15 weeks, at least 20 weeks, at least 30 weeks, etc. The present invention does not cover the duration of the fourth dosing cycle as the last dosing cycle, and the duration of the fourth dosing cycle can be maintained until the time when the required preventive or therapeutic result is achieved, or until the end of the treatment determined by a physician or other healthcare provider.

[0056] In some preferred embodiments, the method for preventing or treating obesity or overweight described in the present invention comprises administering a prophylactically or therapeutically effective amount of a target compound to a patient in need thereof in a dosing schedule consisting of three dosing cycles, and the three dosing cycles include the following: (i) A first dosing cycle in which about 1 unit dose of the target compound is administered weekly for at least 3 to 5 weeks. (ii) A second dosing cycle in which about 2 unit doses of the target compound are administered weekly for at least 3 to 5 weeks. (iii) A third dosing cycle in which about 3 unit doses of the target compound are administered weekly for at least 3 weeks. Here, the unit dose is 2.2 mg to 3.5 mg, and the target compound is selected from mazdutide or a pharmaceutically acceptable salt thereof. At this time, in this embodiment, the dose in the third dosing cycle is a maintenance dose.

[0057] In some more preferred embodiments, the method for preventing or treating obesity or overweight described in the present invention comprises administering a prophylactically or therapeutically effective amount of a target compound to a patient in need thereof in a dosing schedule consisting of three dosing cycles, and the three dosing cycles include the following: (i) Administer the target compound at a dose of about 1 unit per week for a first dosing cycle that lasts for at least 4 weeks. (ii) Administer the target compound at a dose of about 2 units per week for a second dosing cycle that lasts for at least 4 weeks. (iii) Administer the target compound at a dose of about 3 units per week for a third dosing cycle that lasts for at least 4 weeks. Here, the unit dose is 2.2 mg to 3.5 mg, and the target compound is selected from mazdutide or a pharmaceutically acceptable salt thereof. At this time, in this embodiment, the dose in the third dosing cycle is a maintenance dose.

[0058] In some other more preferred embodiments, the method for preventing or treating obesity or overweight described in the present invention comprises administering a prophylactically or therapeutically effective amount of a target compound to a patient in need thereof in a dosing regimen consisting of three dosing cycles, and the three dosing cycles include the following: (i) A first dosing cycle in which the target compound at a dose of about 1 unit is administered weekly for at least 4 weeks. (ii) A second dosing cycle in which the target compound at a dose of about 2 units is administered weekly for at least 4 weeks. (iii) A third dosing cycle in which the target compound at a dose of about 3 units is administered weekly for at least 16 weeks. Here, the unit dose is 2.2 mg to 3.5 mg, and the target compound is selected from mazdutide or a pharmaceutically acceptable salt thereof. At this time, in this embodiment, the dose in the third dosing cycle is a maintenance dose.

[0059] In some other more preferred embodiments, the method for preventing or treating obesity or overweight described in the present invention comprises administering a prophylactically or therapeutically effective amount of a target compound to a patient in need thereof in a dosing regimen consisting of three dosing cycles, and the three dosing cycles include the following: (i) A first dosing cycle in which the target compound at a dose of about 1 unit is administered weekly for at least 4 weeks. (ii) Administer about 2 unit doses of the target compound weekly for a second dosing period that lasts at least 4 weeks. (iii) Administer about 3 unit doses of the target compound weekly for a third dosing period that lasts at least 40 weeks. Here, the unit dose is 2.2 mg to 3.5 mg, and the target compound is selected from mazdutide or a pharmaceutically acceptable salt thereof. At this time, in this embodiment, the dose in the third dosing period is a maintenance dose.

[0060] In some other preferred embodiments, the method for preventing or treating obesity or overweight described in the present invention comprises administering a prophylactically or therapeutically effective amount of the target compound to a patient in need thereof in a dosing schedule consisting of four dosing periods, and the four dosing periods include the following: (i) A first dosing period in which about 1 unit dose of the target compound is administered weekly for at least 3 to 5 weeks. (ii) A second dosing period in which about 2 unit doses of the target compound are administered weekly for at least 3 to 5 weeks. (iii) A third dosing period in which about 3 unit doses of the target compound are administered weekly for at least 3 to 5 weeks. (iv) A fourth dosing period in which about 4 unit doses of the target compound are administered weekly for at least 3 weeks. Here, the unit dose is 2.2 mg to 3.5 mg, and the target compound is selected from mazdutide or a pharmaceutically acceptable salt thereof. At this time, in this embodiment, the dose in the fourth dosing period is a maintenance dose.

[0061] In some other more preferred embodiments, the method for preventing or treating obesity or overweight described in the present invention comprises administering a prophylactically or therapeutically effective amount of the target compound to a patient in need thereof in a dosing schedule consisting of four dosing periods, and the four dosing periods include the following: (i) A first dosing period in which about 1 unit dose of the target compound is administered weekly for at least 4 weeks. (ii) Administer the target compound at a dosage of about 2 units per week for a second dosing cycle that lasts for at least 4 weeks. (iii) Administer the target compound at a dosage of about 3 units per week for a third dosing cycle that lasts for about 4 weeks. (iv) Administer the target compound at a dosage of about 4 units per week for a fourth dosing cycle that lasts for at least 4 weeks. Here, the unit dosage is 2.2 mg to 3.5 mg, and the target compound is selected from mazdutide or a pharmaceutically acceptable salt thereof. At this time, in this embodiment, the dosage in the fourth dosing cycle is a maintenance dosage.

[0062] (Number of administrations) The present invention is not particularly limited with respect to the number of administrations in each dosing cycle, as long as a drug dosage sufficient for the required amount in each dosing cycle is administered. In some embodiments, in each dosing cycle, the target compound is administered to the patient once or multiple times per week. In some embodiments, in each dosing cycle, the target compound is administered to the patient once per week.

[0063] In some preferred embodiments, the method for preventing or treating obesity or overweight described in the present invention comprises administering a prophylactically or therapeutically effective amount of a target compound to a patient in need in a dosing regimen consisting of three dosing cycles, where the dosing regimen includes the following: (i) A first dosing cycle in which about 1 unit dosage of the target compound is administered once per week for at least 3 weeks. (ii) A second dosing cycle in which about 2 unit dosages of the target compound are administered once per week for at least 3 weeks. (iii) A third dosing cycle in which about 3 unit dosages of the target compound are administered once per week for at least 3 weeks, and optionally, (iv) A fourth dosing cycle in which about 4 unit dosages of the target compound are administered once per week for at least 3 weeks. Here, the unit dosage is 2.2 mg to 3.5 mg, and the target compound is selected from mazdutide or a pharmaceutically acceptable salt thereof.

[0064] (Dosage) In the method for preventing or treating obesity or overweight according to the present invention, the dosage approximately doubles as the administration cycle progresses. In each dosing schedule, an initial drug dosage, i.e., a unit dosage, is administered to the patient, and the dosage continuously increases until the patient is administered the maximum effective dosage, i.e., the maintenance dosage, required by the patient as the administration cycle progresses, and thereafter, the dosage does not increase any further.

[0065] In some embodiments, the unit dosage according to the present invention is 2.2 mg to 3.5 mg.

[0066] In some specific embodiments, the unit dosage according to the present invention is 2.2 mg to 3 mg, 2.2 mg to 2.8 mg, 2.4 mg to 2.6 mg, 2.5 mg to 3.5 mg, 2.7 mg to 3.3 mg, 2.9 mg to 3.1 mg, etc.

[0067] In some more specific embodiments, the unit dosage according to the present invention is about 2.2 mg, about 2.3 mg, about 2.4 mg, about 2.5 mg, about 2.6 mg, about 2.7 mg, about 2.8 mg, about 2.9 mg, about 3.0 mg, about 3.1 mg, about 3.2 mg, about 3.3 mg, about 3.4 mg, or about 3.5 mg, etc.

[0068] (Dosing schedule) In the method for preventing or treating obesity or overweight according to the present invention, various different dosing schedules of the target compound are possible, and any of them can achieve effects such as weight loss, blood pressure improvement, blood lipid improvement, serum uric acid level improvement, etc. in the subject.

[0069] In some embodiments, the method for preventing or treating obesity or overweight according to the present invention includes the step of administering the target compound according to the following dosing schedule: In the first administration cycle, about 1 unit dosage of the target compound is administered to the patient every week for at least 3 weeks, Next, in the second dosing cycle, the patient is administered about 2 unit doses of the target compound per week for at least 3 weeks, Next, in the third dosing cycle, the patient is administered about 3 unit doses of the target compound per week for at least 3 weeks. Alternatively, In the first dosing cycle, the patient is administered about 1 unit dose of the target compound per week for at least 3 weeks, Next, in the second dosing cycle, the patient is administered about 2 unit doses of the target compound per week for at least 3 weeks, Next, in the third dosing cycle, the patient is administered about 3 unit doses of the target compound per week for at least 3 weeks, Next, in the fourth dosing cycle, the patient is administered about 4 unit doses of the target compound per week for at least 3 weeks.

[0070] Dosing Schedule I In some specific embodiments, the method for preventing or treating obesity or overweight described in the present invention includes the step of administering a target compound in Dosing Schedule I shown below: In the first dosing cycle, the patient is administered 2.2 mg to 3 mg of the target compound per week for 3 to 5 weeks, Next, in the second dosing cycle, the patient is administered 4.5 mg to 5.5 mg of the target compound per week for 3 to 5 weeks, Next, in the third dosing cycle, the patient is administered 7 mg to 8 mg of the target compound per week for 3 to 5 weeks, Next, in the fourth dosing cycle, the patient is administered 9.5 mg to 10.5 mg of the target compound per week for at least 3 weeks.

[0071] Furthermore, in some specific embodiments, the method for preventing or treating obesity or overweight described in the present invention includes the step of administering a target compound in Dosing Schedule I shown below: In the first dosing cycle, the patient is administered 2.2 mg to 2.8 mg of the target compound per week for about 4 weeks, Next, in the second dosing cycle, the target compound is administered to the patient at 4.7 mg to 5.3 mg per week for about 4 weeks, Next, in the third dosing cycle, the target compound is administered to the patient at 7.2 mg to 7.8 mg per week for about 4 weeks, Next, in the fourth dosing cycle, the target compound is administered to the patient at 9.7 mg to 10.3 mg per week for at least 4 weeks.

[0072] Furthermore, in some specific embodiments, the method for preventing or treating obesity or overweight described in the present invention includes the step of administering the target compound in dosing schedule I shown below: In the first dosing cycle, the target compound is administered to the patient at 2.5 mg per week for about 4 weeks, Next, in the second dosing cycle, the target compound is administered to the patient at 5 mg per week for about 4 weeks Next, in the third dosing cycle, the target compound is administered to the patient at 7.5 mg per week for about 4 weeks, Next, in the fourth dosing cycle, the target compound is administered to the patient at 10 mg per week for at least 4 weeks.

[0073] Still further, in some specific embodiments, the method for preventing or treating obesity or overweight described in the present invention includes the step of administering the target compound in dosing schedule I shown below: In the first dosing cycle, the target compound is administered to the patient once a week at 2.5 mg for about 4 weeks, Next, in the second dosing cycle, the target compound is administered to the patient once a week at 5 mg for about 4 weeks, Next, in the third dosing cycle, the target compound is administered to the patient once a week at 7.5 mg for about 4 weeks, Next, in the fourth dosing cycle, the target compound is administered to the patient once a week at 10 mg for at least 4 weeks.

[0074] Dosing Schedule II In some specific embodiments, the method for preventing or treating obesity or overweight described in the present invention includes the step of administering a target compound according to Administration Plan II shown below: In the first administration cycle, the target compound is administered to the patient at 2.5 mg to 3.5 mg per week for 3 to 5 weeks, Next, in the second administration cycle, the target compound is administered to the patient at 5.5 mg to 6.5 mg per week for 3 to 5 weeks, Next, in the third administration cycle, the target compound is administered to the patient at 8.5 mg to 9.5 mg per week for at least 3 weeks.

[0075] Furthermore, in some specific embodiments, the method for preventing or treating obesity or overweight described in the present invention includes the step of administering a target compound according to Administration Plan II shown below: In the first administration cycle, the target compound is administered to the patient at 2.7 mg to 3.3 mg per week for about 4 weeks, Next, in the second administration cycle, the target compound is administered to the patient at 5.7 mg to 6.3 mg per week for about 4 weeks, Next, in the third administration cycle, the target compound is administered to the patient at 8.7 mg to 9.3 mg per week for at least 4 weeks.

[0076] Even further, in some specific embodiments, the method for preventing or treating obesity or overweight described in the present invention includes the step of administering a target compound according to Administration Plan II shown below: In the first administration cycle, the target compound is administered to the patient at 3 mg per week for about 4 weeks, Next, in the second administration cycle, the target compound is administered to the patient at 6 mg per week for about 4 weeks, Next, in the third administration cycle, the target compound is administered to the patient at 9 mg per week for at least 4 weeks.

[0077] Furthermore, in some specific embodiments, the method for preventing or treating obesity or overweight described in the present invention includes the step of administering a target compound according to the following dosing schedule II: In the first dosing cycle, the target compound is administered to the patient at a dose of 3 mg once a week for about 4 weeks, Next, in the second dosing cycle, the target compound is administered to the patient at a dose of 6 mg once a week for about 4 weeks, Next, in the third dosing cycle, the target compound is administered to the patient at a dose of 9 mg once a week for at least 4 weeks.

[0078] In some other specific embodiments, the method for preventing or treating obesity or overweight described in the present invention includes the step of administering a target compound according to the following dosing schedule II: In the first dosing cycle, the target compound is administered to the patient at a dose of 2.5 mg to 3.5 mg per week for 3 to 5 weeks, Next, in the second dosing cycle, the target compound is administered to the patient at a dose of 5.5 mg to 6.5 mg per week for 3 to 5 weeks, Next, in the third dosing cycle, the target compound is administered to the patient at a dose of 8.5 mg to 9.5 mg per week for at least 16 weeks.

[0079] Furthermore, in some specific embodiments, the method for preventing or treating obesity or overweight described in the present invention includes the step of administering a target compound according to the following dosing schedule II: In the first dosing cycle, the target compound is administered to the patient at a dose of 2.7 mg to 3.3 mg per week for about 4 weeks, Next, in the second dosing cycle, the target compound is administered to the patient at a dose of 5.7 mg to 6.3 mg per week for about 4 weeks, Next, in the third dosing cycle, the target compound is administered to the patient at a dose of 8.7 mg to 9.3 mg per week for at least 16 weeks.

[0080] Furthermore, in some other specific embodiments, the method for preventing or treating obesity or overweight described in the present invention includes the step of administering a target compound according to Administration Schedule II shown below: In the first administration cycle, 3 mg of the target compound is administered to the patient once a week for about 4 weeks, Next, in the second administration cycle, 6 mg of the target compound is administered to the patient once a week for about 4 weeks, Next, in the third administration cycle, 9 mg of the target compound is administered to the patient once a week for at least 16 weeks.

[0081] Furthermore, in some other specific embodiments, the method for preventing or treating obesity or overweight described in the present invention includes the step of administering a target compound according to Administration Schedule II shown below: In the first administration cycle, 3 mg of the target compound is administered to the patient once a week for about 4 weeks, Next, in the second administration cycle, 6 mg of the target compound is administered to the patient once a week for about 4 weeks, Next, in the third administration cycle, 9 mg of the target compound is administered to the patient once a week for at least 16 weeks.

[0082] In some other specific embodiments, the method for preventing or treating obesity or overweight described in the present invention includes the step of administering a target compound according to Administration Schedule II shown below: In the first administration cycle, 2.5 mg to 3.5 mg of the target compound is administered to the patient once a week for 3 to 5 weeks, Next, in the second administration cycle, 5.5 mg to 6.5 mg of the target compound is administered to the patient once a week for 3 to 5 weeks, Next, in the third administration cycle, 8.5 mg to 9.5 mg of the target compound is administered to the patient once a week for at least 40 weeks.

[0083] Furthermore, in some other specific embodiments, the method for preventing or treating obesity or overweight described in the present invention includes the step of administering a target compound according to the following dosing schedule II: In the first dosing cycle, the target compound is administered to the patient at 2.7 mg to 3.3 mg per week for about 4 weeks, Next, in the second dosing cycle, the target compound is administered to the patient at 5.7 mg to 6.3 mg per week for about 4 weeks, Next, in the third dosing cycle, the target compound is administered to the patient at 8.7 mg to 9.3 mg per week for at least 40 weeks.

[0084] Even further, in some other specific embodiments, the method for preventing or treating obesity or overweight described in the present invention includes the step of administering a target compound according to the following dosing schedule II: In the first dosing cycle, the target compound is administered to the patient at 3 mg per week for about 4 weeks, Next, in the second dosing cycle, the target compound is administered to the patient at 6 mg per week for about 4 weeks, Next, in the third dosing cycle, the target compound is administered to the patient at 9 mg per week for at least 40 weeks.

[0085] Still further, in some other specific embodiments, the method for preventing or treating obesity or overweight described in the present invention includes the step of administering a target compound according to the following dosing schedule II: In the first dosing cycle, the target compound is administered to the patient once a week at 3 mg for about 4 weeks, Next, in the second dosing cycle, the target compound is administered to the patient once a week at 6 mg for about 4 weeks, Next, in the third dosing cycle, the target compound is administered to the patient once a week at 9 mg for at least 40 weeks.

[0086] (Route of administration) The present invention is not particularly limited with respect to the specific manner of administering the target compound to the subject. In some embodiments, the administration method described in the present invention is administration by injection. In some preferred embodiments, the administration described in the present invention is administration by subcutaneous injection.

[0087] <Second Aspect> The present invention provides a method for improving body weight in a patient in need thereof, the method comprising administering a prophylactically or therapeutically effective amount of a target compound to the patient in an administration schedule consisting of at least three administration cycles, wherein the at least three administration cycles include: (i) A first administration cycle in which about one unit dose of the target compound is administered weekly for at least three weeks. (ii) A second administration cycle in which about two unit doses of the target compound are administered weekly for at least three weeks. (iii) A third administration cycle in which about three unit doses of the target compound are administered weekly for at least three weeks, and optionally, (iv) A fourth administration cycle in which about four unit doses of the target compound are administered weekly for at least three weeks. Here, the unit dose is 2.2 mg to 3.5 mg, and the target compound is selected from mazdutide or a pharmaceutically acceptable salt thereof.

[0088] Here, the limitations on the duration of the administration cycle, the number of administrations, the dosage, the administration schedule, and the administration method are as described in the <First Aspect> of the present invention.

[0089] <Third Aspect> The present invention provides a target compound for preventing or treating obesity or overweight in a patient in need thereof, wherein in an administration schedule consisting of at least three administration cycles, a prophylactically or therapeutically effective amount of the target compound is administered to the patient in need thereof, and the at least three administration cycles include: (i) A first administration cycle in which about one unit dose of the target compound is administered weekly for at least three weeks. (ii) The second dosing cycle, in which about two unit doses of the target compound are administered weekly for at least three weeks, (iii) The third dosing cycle, in which about three unit doses of the target compound are administered weekly for at least three weeks, and optionally, (iv) The fourth dosing cycle, in which about four unit doses of the target compound are administered weekly for at least three weeks, wherein the unit dose is 2.2 mg to 3.5 mg, and the target compound is selected from mazdutide or a pharmaceutically acceptable salt thereof.

[0090] Here, the limitations on the duration, frequency, dose, dosing schedule, and dosing method of the dosing cycle are as described in the <first aspect> of the present invention.

Examples

[0091] The present invention is further illustrated by the following examples, but any example or combination thereof should not be construed as limiting the scope or embodiments of the present invention. The scope of the present invention is defined by the appended claims, and those skilled in the art, in combination with the present specification and general common knowledge in this field, can clearly understand the scope defined by the claims. Without departing from the spirit and scope of the present invention, those skilled in the art can make any modifications or changes to the technical solutions of the present invention, and these modifications or changes are also included within the scope of the present invention.

[0092] For those not specifying specific conditions in the examples, they are carried out according to normal conditions or the conditions recommended by the manufacturer. All reagents or equipment are not specified by the manufacturer, and all are ordinary commercially available products. To better illustrate the present invention, a number of specific details are provided in the following specific embodiments. Those skilled in the art should understand that the present invention can be implemented without specific specific details. In some other embodiments, to emphasize the gist of the present invention, methods, means, devices, and steps well known to those skilled in the art are not described in detail.

[0093] Unless otherwise defined, all technical and scientific terms used in this specification have the same meaning as commonly understood by one of ordinary skill in the art. Unless otherwise specified, the units used in this specification are all international standard units, and it should be understood that the numerical values and numerical ranges appearing in the present invention include inevitable systematic errors.

[0094] Example 1. Clinical Trial of Mazdutide Administration Schedule 1. Test Drug The Mazdutide formulation is injectable mazdutide, which consists of 2 mg of mazdutide, tris(hydroxymethyl)aminomethane without active ingredient, mannitol and sucrose. The contents of the vial were redissolved with sterile water for injection to obtain a clear solution of mazdutide.

[0095] The placebo is a mazdutide mimic, which consists of tris(hydroxymethyl)aminomethane, mannitol and sucrose, which are inert ingredients. The contents of the vial were redissolved with sterile water for injection to obtain a clear solution of inert ingredients.

[0096] In this study, the formulation standard is 2 mg / vial, and the placebo standard is consistent with the formulation.

[0097] 2. Registration Criteria / Exclusion Criteria for Subjects A) Main Selection Criteria: 1. The age is 18 to 75 years old (including both endpoint values), male or female.

[0098] 2. Obese subjects with BMI ≥ 28.0 kg / m 2 or subjects with 24 ≤ BMI < 28.0 kg / m 2is overweight and accompanied by at least one of the following: i. having strong appetite, experiencing unbearable hunger before meals, and having a relatively large food intake per meal; ii. having one or more of prediabetes (impaired fasting glucose and / or impaired glucose tolerance), hypertension, dyslipidemia, fatty liver (within 6 months before screening); iii. having pain in the joints supporting the weight; iv. having dyspnea due to obesity or obstructive sleep apnea syndrome.

[0099] 3. During screening, if it is controlled by simple diet and exercise for at least 12 weeks, the change in body weight is less than 5%.

[0100] B) Main exclusion criteria: 1. Using any one of the following drugs or treatments before screening: 1) Having used a GLP-1 receptor (GLP-1R) agonist or a GLP-1R / GCGR agonist in the past. 2) Using drugs that affect body weight, including systemic steroid hormone therapy drugs (intravenous, oral or intra-articular administration), metformin, SGLT2 inhibitors, thiazolidinediones (TZD), tricyclic antidepressants, drugs for treating mental disorders or sedatives (such as imipramine, amitriptyline, mirtazapine, paroxetine, phenelzine, chlorpromazine, thioridazine, clozapine, olanzapine, valproic acid, valproic acid derivatives, lithium salts, etc.) within 3 months before screening. 3) Using traditional Chinese medicines or health foods that affect body weight within 3 months before screening. 4) Having used or currently using weight loss drugs such as sibutramine hydrochloride, orlistat, ionamin, phenylpropanolamine, mazindol, phentermine, amfepramone, lorcaserin, phentermine / topiramate mixture, naltrexone / bupropion hydrochloride mixture, etc. within 3 months before screening. 5) Having participated in other clinical trials (having received treatment with investigational drugs) within 3 months before screening.

[0101] 2. Prior to screening, there is a history or evidence of any one of the following diseases: 1) Diagnosed as a diabetes subject according to the WHO 1999 criteria. 2) At the time of screening, the fasting venous blood glucose level is ≥ 7.0 mmol / L, or at 2 hours after glucose load in a 75 g oral glucose tolerance test (OGTT), the venous blood glucose level is ≥ 11.1 mmol / L (for subjects with a fasting blood glucose level of 6.1 mmol / L - 7.0 mmol / L at the time of screening, it is necessary to collect the venous blood glucose level at 2 hours after OGTT glucose load for confirmation). 3) A subject with retinopathy in the past or at the time of screening. 4) Secondary or drug-induced obesity, including elevated cortisol hormone (e.g., Cushing's syndrome), obesity due to pituitary and hypothalamic damage, obesity due to weight loss drug reduction / discontinuation, etc. 5) Has undergone surgery for weight loss in the past or has received acupuncture treatment for weight loss within 1 year before screening. 6) Has a history of depression in the past or has a history of severe mental illnesses such as schizophrenia and bipolar disorder in the past. 7) Hypertension that still cannot be stably controlled at the time of screening after at least 4 weeks of treatment with antihypertensive drugs, defined as systolic blood pressure > 140 mmHg and / or diastolic blood pressure > 100 mmHg. 8) At the time of screening, the systolic blood pressure is < 90 mmHg and / or the diastolic blood pressure is < 50 mmHg. 9) At the time of screening, there is a history of malignant tumors (excluding already cured basal cell carcinoma of the skin and cervical intraepithelial neoplasia). 10) At the time of screening, there are heart-related diseases (such as angina pectoris, myocardial infarction, cardiomyopathy, acute or chronic heart failure, etc.). 11) Suffered a hemorrhagic stroke, ischemic stroke, or transient cerebral ischemia attack within 6 months before screening. 12) At the time of screening, there is a history of thyroid C cell carcinoma, a history of MEN (multiple endocrine neoplasia) type 2A or 2B syndrome, or a related family history. 13) At the time of screening, there is a history of acute or chronic pancreatitis, a history of cholecystitis, or a history of pancreatic injury. 14) At the time of screening, is there a chronic gastrointestinal disease or systemic disease that may affect gastrointestinal motility, or has a drug that may change gastrointestinal motility, appetite, or absorption been used within 3 months before screening? 15) There are limb deformities or amputations, and it is impossible to accurately determine indicators such as height and weight. 16) There has been a large or medium-scale surgery, severe trauma, or severe infectious disease within 1 month before screening, and the researcher has determined that it is not appropriate for the subject to participate in this study. 17) There has been a past suicide tendency or suicide behavior. 18) There is a planned surgery during the test period, but outpatient surgeries that the researcher has determined will not affect the safety of the subject and the test results are excluded. 19) At the time of screening, the subject is positive for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or syphilis antibody. 20) There is a history of alcohol abuse within 1 month before screening. The weekly average alcohol intake exceeds 21 units for men and 14 units for women, or there is no intention to stop drinking (1 unit = 360 mL of beer, or 150 mL of red wine, or 45 mL of distilled liquor / white liquor) 24 hours before the administration date and throughout the study period. 21) At the time of screening, the urine screening test for drug and narcotic abuse is positive.

[0102] 3. Any one of the laboratory test indicators meets the following criteria (if there is a clear reason for reconfirmation at the time of screening, reconfirmation can be performed within 1 week, and the researcher needs to record the reason for reconfirmation): 1) At the time of screening, serum calcitonin ≥ 15 ng / L. 2) At the time of screening, alanine aminotransferase ≥ 2.0 × ULN and / or aspartate aminotransferase ≥ 2.0 × ULN and / or total bilirubin ≥ 1.0 × ULN and / or alkaline phosphatase ≥ 2.0 × ULN. 3) At the time of screening, estimated using the CKD-EPI formula, glomerular filtration rate eGFR < 60 mL / min / 1.73m 2 is present. 4) At the time of screening, thyroid function (FT3, FT4 or TSH) is abnormal. 5) At the time of screening, fasting triglyceride ≥ 5.64 mmol / L (500 mg / dL), and if the subject is receiving lipid-regulating therapy, it is necessary to stabilize the drug dose before screening for 30 days. 6) At the time of screening, blood amylase or lipase > 2.0 × ULN. 7) At the time of screening, the international normalized ratio (INR) of prothrombin time exceeded the upper limit of the normal value range.

[0103] 4. At the time of screening, a heart rate < 50 beats / min or > 90 beats / min was shown on a 12-lead electrocardiogram.

[0104] 5. At the time of screening, the following clinically significant 12-lead electrocardiogram (ECGs) abnormalities: in the case of not using a pacemaker, the appearance of second-degree or third-degree atrioventricular block, QT prolongation syndrome or QTcF > 450 ms (see Appendix 3 for the calculation formula), PR interval < 120 ms or PR interval > 220 ms, QRS > 120 ms, left bundle branch block or right bundle branch block, pre-excitation syndrome or severe arrhythmia requiring treatment appeared.

[0105] 6. Women who are pregnant or breastfeeding, men or women who may be pregnant are not desired to use contraception throughout the study period.

[0106] 7. Within 3 months before screening, the blood donation volume and / or blood loss volume ≥ 400 mL, or bone marrow was donated, or there is abnormal hemoglobinopathy, hemolytic anemia, sickle cell anemia, or hemoglobin < 110 g / L (male) or < 100 g / L (female).

[0107] 8. The researcher believes that the subject has any other factors that may affect the treatment effect or safety evaluation of this study and is considered inappropriate for participation in this study.

[0108] 3. Administration method and process There are a total of 5 cohorts in this study, and the subjects in each cohort were randomly divided into the mazdutide treatment group (n = 8) and the placebo group (n = 4) at a ratio of 2:1. In Cohort 1, Cohort 2, Cohort 3, Cohort 4, and Cohort 5, the administration plans for subcutaneous injection of mazdutide or placebo are as follows: Drug specification: The placebo specification conforms to the formulation. Administration method: Subcutaneous injection, once a week. Administration plan: Cohort 1 (referred to as the 3 mg cohort): Administered 1.0 mg continuously for 4 weeks + 2.0 mg continuously for 4 weeks + 3.0 mg continuously for 4 weeks. Cohort 2 (referred to as the 4.5 mg cohort): Administered 1.5 mg continuously for 4 weeks + 3.0 mg continuously for 4 weeks + 4.5 mg continuously for 4 weeks. Cohort 3 (referred to as the 6 mg cohort): Administered 2.0 mg continuously for 4 weeks + 4.0 mg continuously for 4 weeks + 6.0 mg continuously for 4 weeks. Cohort 4 (referred to as the 10 mg cohort): Administered 2.5 mg continuously for 4 weeks + 5.0 mg continuously for 4 weeks + 7.5 mg continuously for 4 weeks + 10.0 mg continuously for 4 weeks. Cohort 5 (referred to as the 9 mg cohort): Administered 3.0 mg continuously for 4 weeks + 6.0 mg continuously for 4 weeks + 9.0 mg continuously for 4 weeks.

[0109] 4. Experimental results This study included a total of five cohorts, and all different doses of mazdutide showed significant treatment effects on weight loss. After administration for 12 weeks, in Cohort 1 (1 mg - 2 mg - 3 mg), Cohort 2 (1.5 mg - 3 mg - 4.5 mg), Cohort 3 (2 mg - 4 mg - 6 mg), and Cohort 5 (3 mg - 6 mg - 9 mg), the least-squares mean values of the percentage change in the weight of the subjects in the mazdutide group from the baseline were -4.81%, -6.40%, -6.05%, and -11.7% respectively. After administration for 16 weeks, in Cohort 4 (2.5 mg - 5 mg - 7.5 mg - 10 mg), the least-squares mean value of the percentage change in the weight of the subjects in the mazdutide group from the baseline was -9.5%. The above results are shown in Figure 1. In Cohort 4 and Cohort 5, the results of the average change in the BMI of the subjects from the baseline are shown in Figure 2.

[0110] Thus, each dose group showed good treatment effects on weight loss in the subjects, and after 12 weeks or 16 weeks of continuous administration, the weight loss effect still did not reach the plateau stage. The administration plan of Cohort 5 of the present invention has a particularly significant weight loss effect in patients.

[0111] In addition, past studies have shown that the treatment effect of GLP-1 drugs on weight loss is dose-dependent. By comparing the administration plans of Cohort 4 and Cohort 5 of the present invention, it can be found that the dose in the administration plan of Cohort 5 is lower and the treatment period is shorter compared to the administration plan of Cohort 4. It is proved that Cohort 5 of the present invention achieves the optimal weight loss effect with relatively low doses and a relatively short time through a specific administration plan, rather than bringing a better weight loss treatment effect due to an increase in dose and time, breaking the understanding of the administration plan of GLP-1 drugs in the prior art and having important prospects for clinical use.

[0112] Meanwhile, based on the therapeutic effect of weight loss, different doses of mazdutide among the five cohorts of the present invention also show relatively good beneficial effects in improving indicators such as blood pressure, blood lipid, and serum uric acid levels. Here, the statistical results of the average changes from the baselines of the blood pressure, blood lipid, and serum uric acid levels of the subjects in Cohort 4 and Cohort 5 of the present invention are shown in Figures 3 to 5.

[0113] In addition, by comparing the weight loss rates of patients after administering other similar drugs according to different dosing regimens for 12 weeks. For example, the 2.4 mg dosing regimen of Semaglutide (subcutaneously inject 2.4 mg of Semaglutide once a week, specifically refer to Khoo TK, Lin J. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 Jul 1, 385(1):e4.) and the 10 mg or 15 mg dosing regimens of Tirzepatide (respectively: subcutaneously inject Tirzepatide starting from a dose of 2.5 mg once a week, and increase the dose by 2.5 mg every 4 weeks until reaching 10 mg or 15 mg, specifically refer to Frias JP, Davies MJ, Rosenstock J, Perez Manghi FC, Fernandez Lando L, Bergman BK, Liu B, Cui X, Brown K, SURPASS-2 Investigators. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N Engl J Med. 2021 Aug 5, 385(6):503-515.), the mazdutide dosing regimen of Cohort 5 of the present invention is still found to show a particularly significant weight loss effect in the subjects, and the above results are shown in Figure 6.

[0114] Safety results: In all five cohorts, there were no dose adjustments of the investigational drug during the study process. Most treatment-emergent adverse events (TEAEs) were mild, no severe TEAEs were reported, there were no TEAEs leading to permanent drug discontinuation, no treatment-emergent serious adverse events (TESAEs) occurred during the treatment period, and no severe hypoglycemic events occurred. The overall tolerance and safety of patients during the administration process were good, and it was proven that the dosing regimen provided by the present invention has high safety in clinical administration.

[0115] Example 2, Further Clinical Trials of the Mazdutide Dosing Regimen 1. Investigational Drug Same as in Example 1.

[0116] 2. Inclusion / Exclusion Criteria for Subjects A) Main Inclusion Criteria: 1. Subjects are male or female, aged 18 to 75 years (including both endpoint values).

[0117] 2. Obese subjects with a BMI ≥ 30.0 kg / m 2 2.

[0118] 3. The weight change of the subject before and after the lead-in period is less than 5.0%. The calculation formula is: percentage change in weight = |(weight before randomization - weight on the lead-in day) / weight before randomization| * 100%.

[0119] 4. Understand the research procedures and methods, have the willingness to complete the trial strictly in accordance with the clinical trial protocol, and be able to voluntarily sign the informed consent.

[0120] B) Main Exclusion Criteria: 1. The investigator suspects that the subject may be allergic to the investigational drug or its components or similar drugs.

[0121] 2. Before screening, if the subject is controlled by a simple diet and exercise for at least 12 weeks, the weight change is > 5.0% (main complaint).

[0122] 3. Before screening, use any one of the following drugs or treatments: 1) Use a GLP-1 receptor (GLP-1R) agonist or GLP-1R / GCGR agonist or GIPR / GLP-1R agonist or GIPR / GLP-1R / GCGR agonist within 3 months before screening. 2) Use drugs that affect body weight, including systemic steroid hormone therapeutic agents (intravenous, oral or intra-articular administration), tricyclic antidepressants, therapeutic agents for mental diseases or sedatives (imipramine, amitriptyline, mirtazapine, paroxetine, phenelzine, chlorpromazine, thioridazine, clozapine, olanzapine, valproic acid, valproic acid derivatives, lithium salts, etc.) within 3 months before screening. 3) Use Chinese herbal medicines, health foods, replacement diet foods, etc. that affect body weight within 3 months before screening. 4) Use or currently use weight loss drugs such as sibutramine hydrochloride, orlistat, ionamin, phenylpropanolamine, mazindol, phentermine, amfepramone, lorcaserin, phentermine / topiramate mixture, naltrexone / bupropion hydrochloride mixture, etc. within 3 months before screening. 5) Use hypoglycemic drugs such as metformin, SGLT2 inhibitors, thiazolidinedione (TZD), etc. within 3 months before screening. 6) Participate in other clinical trials (already received treatment with the investigational drug) within 3 months before screening.

[0123] 4. Have a history or evidence of any one of the following diseases: 1) At the time of screening, the patient has HbA1c ≧ 6.5% or has been diagnosed with type I or type II diabetes in the past. 2) At the time of screening, the fasting venous blood glucose level is ≥ 7.0 mmol / L, or at 2 hours after glucose load in the 75 g oral glucose tolerance test (OGTT), the venous blood glucose level is ≥ 11.1 mmol / L (for subjects with a fasting blood glucose level of 6.1 mmol / L - 6.9 mmol / L at the time of screening, it is necessary to collect the venous blood glucose level 2 hours after OGTT glucose load for confirmation). 3) A patient who has had retinopathy in the past or at the time of screening. 4) Severe hypoglycemia or recurrent symptomatic hypoglycemia (≥ 2 times within half a year) has occurred in the past. 5) Secondary disease or drug-induced obesity, including elevated cortisol hormone (e.g., Cushing's syndrome), obesity due to damage to the pituitary and hypothalamus, and obesity due to weight loss drug reduction / discontinuation. 6) Has had surgery for weight loss in the past (excluding acupuncture treatment, liposuction, and abdominal liposuction for weight loss 1 year before screening). 7) There are plans for surgery for weight loss or acupuncture treatment for weight loss, liposuction, and abdominal liposuction during the study period. 8) Has a history of moderate to severe depression in the past, or has a history of severe mental illnesses such as schizophrenia or bipolar disorder in the past. 9) Has had suicidal tendencies or suicidal behavior in the past. 10) At the time of screening or randomization, the PHQ (depression screening tool) questionnaire score is ≥ 15 points. 11) At the time of screening or randomization, the C-SSRS (Columbia Suicide Severity Rating Scale) questionnaire is in category 4 or 5. 12) Uncontrolled hypertension exists within 1 month before screening, defined as systolic blood pressure ≥ 160 mmHg and / or diastolic blood pressure ≥ 100 mmHg (when using antihypertensive drugs, it is necessary to stabilize for 1 month). 13) Has a history of malignant tumors (excluding already cured basal cell carcinoma of the skin and cervical intraepithelial neoplasia) in the past or at the time of screening. 14) Having a history of previous myocardial infarction, angina pectoris, acute or chronic heart failure, cardiomyopathy, or having undergone cardiac surgery such as percutaneous coronary intervention therapy, coronary artery bypass grafting, etc., or having significantly abnormal cardiac function on echocardiogram, and after evaluation by the researcher, presenting that participation in this study is not appropriate. 15) Having had a hemorrhagic stroke, ischemic stroke, or transient cerebral ischemia attack within 6 months before screening. 16) Having a past history of thyroid C cell cancer, a past history of MEN (multiple endocrine neoplasia) 2A or 2B, or a related family history. 17) Having a past history of acute or chronic pancreatitis, a past history of cholecystitis, or a past history of pancreatic injury. 18) Having limb deformities or amputations, and being unable to accurately determine indicators such as height and weight. 19) Having had major or medium-scale surgery, severe trauma, or severe infectious diseases within 1 month before screening, and the researcher determining that participation in this study is not appropriate. 20) Having a scheduled surgery during the test period, but excluding outpatient surgeries where the researcher determines that it will not affect the safety of the subject and the test results. 21) Subjects who are positive for human immunodeficiency virus (HIV) antibodies, hepatitis C virus (HCV) antibodies, or syphilis antibodies at the time of screening. 22) Being positive for hepatitis B surface antigen (HBsAg) at the time of screening and having hepatitis B virus DNA ≥ 1000 IU / mL (not eligible for registration if using anti-hepatitis B virus drugs at the time of screening). 23) Having a history of alcohol and drug abuse at the time of screening. The weekly average alcohol intake exceeding 21 units for men and 14 units for women, or having no intention to abstain from drinking (1 unit = 360 mL of beer, or 150 mL of red wine, or 45 mL of distilled liquor / white liquor) 24 hours before the dosing day and throughout the study period.

[0124] 5. At the time of screening, any one of the laboratory test indicators meets the following criteria (if there is a clear reason for reconfirmation, reconfirmation can be carried out within one week, and the researcher needs to record the reason for reconfirmation): 1) Serum calcitonin ≥ 20 ng / L (pg / mL). 2) Alanine aminotransferase ≥ 3.0 × upper limit of normal value (Upper Limit of Normal Value, ULN) and / or aspartate aminotransferase ≥ 3.0 × ULN and / or total bilirubin ≥ 1.5 × ULN. 3) Estimated using the CKD-EPI formula, and the glomerular filtration rate eGFR < 60 mL / min / 1.73m 2 is the case. 4) There is thyroid function abnormality (TSH > 6 mIU / L or < 0.4 mIU / L). 5) Fasting triglyceride ≥ 5.64 mmol / L (500 mg / dL). 6) Blood amylase or lipase > 2.0 × ULN. 7) The international normalized ratio (INR) of prothrombin time exceeds the upper limit of the normal value range. 8) Hemoglobin < 110 g / L (male) or < 100 g / L (female).

[0125] 6. At the time of screening, a 12-lead electrocardiogram shows a heart rate < 50 beats / min or > 100 beats / min.

[0126] 7. At the time of screening, the following clinically significant 12-lead electrocardiogram (ECGs) abnormalities: second-degree or third-degree atrioventricular block, long QT syndrome or QTcF > 500 ms (for the calculation formula, refer to Appendix 4), left bundle branch block or right bundle branch block, pre-excitation syndrome or other significant arrhythmias (excluding sinus arrhythmia).

[0127] 8. Women who are pregnant or breastfeeding, men or women who may be pregnant do not wish to avoid pregnancy throughout the study period.

[0128] 9. Within 3 months before screening, the blood donation volume and / or blood loss volume ≥ 400 mL, or bone marrow donation has been performed, or there is abnormal hemoglobinopathy, hemolytic anemia, or sickle cell anemia.

[0129] 10. The researcher believes that the subject has any other factors that may affect the treatment effect or safety evaluation of this study and is not considered suitable for participating in this study.

[0130] 3. Administration method and process In this study, about 80 subjects are planned to be enrolled. Subjects who pass the screening will introduce placebo for 2 weeks, and after successful introduction, they will follow mazdutide: placebo = 3:1 ratio, be randomly enrolled, and administered under the dosing plan. After the administration to the subjects is completed, follow-up regarding drug withdrawal for 12 weeks can be carried out. Drug specification: The placebo specification conforms to the formulation. Administration method: Subcutaneous injection, once a week. Dosing plan: Administered continuously at 3.0 mg for 4 weeks + 6.0 mg for 4 weeks + 9.0 mg for 16 weeks or 40 weeks continuously.

[0131] 4. Experimental results In this study stage, 80 subjects are enrolled. Subjects who pass the screening will introduce placebo for 2 weeks, and after successful introduction, they will be randomly divided into the mazdutide group or the placebo group. The administration method is as follows: Administered at 3.0 mg QW for 4 weeks + 6.0 mg QW for 4 weeks + 9.0 mg QW for 16 weeks. After reaching the primary endpoint at 24 weeks, the subject can choose to undergo 24-week extended treatment.

[0132] The current study has already reached the primary endpoint, and the results show that the percentage changes from the baseline weight in the mazdutide group and the placebo group after 24 weeks of continuous administration are -13.25% and 2.11% respectively. Compared with the placebo group, the difference in the percentage change from the baseline weight after 24 weeks of continuous administration in the mazdutide group is -15.36% (the p-value is less than 0.0001). The change values from the baseline weight in the mazdutide group and the placebo group are -12.55 kg and 2.12 kg respectively. Compared with the placebo group, the difference in the percentage change from the baseline weight after 24 weeks of continuous administration in the mazdutide group is -14.67 kg (the p-value is less than 0.0001). After 24 weeks of continuous administration, the weight of the subjects in the mazdutide group decreased by at least 5%, 10%, 15% and 20% from the baseline weight of the subjects, which were 81.7%, 65.0%, 31.7% and 21.7% respectively, while in the placebo group, there were no subjects whose weight loss rate reached 5% or more.

[0133] As can be seen, by increasing the administration time of the maintenance dose (for example, continuously administering a maintenance dose of 9.0 mg for 16 weeks or 40 weeks, etc.) compared with the administration plan of cohort 5 in Example 1 (continuously administering for 12 weeks), the therapeutic effect of weight loss in obese subjects can be further improved.

[0134] Regarding safety, so far, the mazdutide treatment group has generally shown good tolerance and safety. The dropout rate of the treatment group is generally lower than that of the placebo group. In the treatment group, there were no subjects who terminated treatment early due to adverse events, and no serious adverse events occurred. Except for COVID-19 infection, the most frequently occurring adverse events during the treatment period were gastrointestinal-related adverse events, and most of them were mild or moderate, all of which were transient. This demonstrates that the administration plan provided by the present invention has high safety in clinical administration.

Claims

1. A pharmaceutical composition for preventing or treating obesity or overweight, comprising a preventive or therapeutically effective amount of mazdutide or a pharmaceutically acceptable salt thereof, wherein the pharmaceutical composition is administered to a patient in need in a dosing regimen comprising a first dosing cycle, a second dosing cycle, and a third dosing cycle, wherein the dosing cycle comprises: (i) During the first administration cycle, administer approximately one unit dose of mazdutide or a pharmaceutically acceptable salt thereof weekly for at least three weeks. (ii) In the second administration cycle, administer approximately 2 units of mazdutide or a pharmaceutically acceptable salt thereof weekly for at least 3 weeks. (iii) In the third administration cycle, administer approximately 3 units of mazdutide or a pharmaceutically acceptable salt thereof weekly for at least 3 weeks. Here, the unit dose is 2.2 mg to 3.5 mg. Pharmaceutical composition.

2. The unit dose is approximately 3 mg, 2.2 mg to 3 mg, 2.2 mg to 2.8 mg, 2.4 mg to 2.6 mg, 2.5 mg to 3.5 mg, 2.7 mg to 3.3 mg, or 2.9 mg to 3.1 mg. Selectively, the unit dose is approximately 2.2 mg, approximately 2.3 mg, approximately 2.4 mg, approximately 2.5 mg, approximately 2.6 mg, approximately 2.7 mg, approximately 2.8 mg, approximately 2.9 mg, approximately 3.1 mg, approximately 3.2 mg, approximately 3.3 mg, approximately 3.4 mg, or approximately 3.5 mg. The pharmaceutical composition according to claim 1.

3. The duration of the final administration cycle in the aforementioned administration plan is at least 3 weeks, preferably at least 4 weeks, and the duration of each of the remaining administration cycles is independently 3 to 5 weeks, preferably about 4 weeks. Selectively, The third administration cycle is administered as the final administration cycle in the administration plan, and the duration of the third administration cycle is at least three weeks, preferably at least four weeks. or, The fourth administration cycle is administered as the final administration cycle in the administration plan, and the duration of the fourth administration cycle is at least three weeks, preferably at least four weeks. The pharmaceutical composition according to claim 1.

4. In each administration cycle, mazdutide or a pharmaceutically acceptable salt thereof is administered to the patient once or more times per week. Preferably, in each administration cycle, mazdutide or a pharmaceutically acceptable salt thereof is administered to the patient once a week. The pharmaceutical composition according to claim 1.

5. The pharmaceutical composition according to claim 1, comprising mazdutide or a pharmaceutically acceptable salt thereof, administered in the following dosage schedule: In the first administration cycle, the patient is administered approximately 2.5 mg to 3.5 mg of mazdutide or a pharmaceutically acceptable salt thereof weekly for approximately 3 to 5 weeks. Next, in the second administration cycle, the patient is administered approximately 5.5 mg to 6.5 mg of mazdutide or a pharmaceutically acceptable salt thereof weekly for approximately 3 to 5 weeks. Next, in the third administration cycle, the patient is administered approximately 8.5 mg to 9.5 mg of mazdutide or a pharmaceutically acceptable salt thereof weekly for at least approximately three weeks. Selectively, in the first administration cycle, the patient is administered approximately 2.7 mg to 3.3 mg of mazdutide or a pharmaceutically acceptable salt thereof weekly for approximately 4 weeks, preferably approximately 3 mg of mazdutide or a pharmaceutically acceptable salt thereof weekly for approximately 4 weeks, and more preferably approximately 3 mg of mazdutide or a pharmaceutically acceptable salt thereof once a week for approximately 4 weeks. Selectively, in the second administration cycle, the patient is administered 5.7 mg to 6.3 mg of mazdutide or a pharmaceutically acceptable salt thereof weekly for about four weeks, preferably about 6 mg of mazdutide or a pharmaceutically acceptable salt thereof weekly for about four weeks, and more preferably about 6 mg of mazdutide or a pharmaceutically acceptable salt thereof once a week for about four weeks. Selectively, in the third administration cycle, the patient is administered 8.7 mg to 9.3 mg of mazdutide or a pharmaceutically acceptable salt thereof weekly for at least four weeks, preferably about 9 mg of mazdutide or a pharmaceutically acceptable salt thereof weekly for at least four weeks, and more preferably about 9 mg of mazdutide or a pharmaceutically acceptable salt thereof once a week for at least four weeks. Selectively, in the third administration cycle, the patient is administered 8.7 mg to 9.3 mg of mazdutide or a pharmaceutically acceptable salt thereof weekly for at least 16 weeks, preferably about 9 mg of mazdutide or a pharmaceutically acceptable salt thereof weekly for at least 16 weeks, and more preferably about 9 mg of mazdutide or a pharmaceutically acceptable salt thereof once a week for at least 16 weeks. Selectively, in the third administration cycle, the patient is administered 8.7 mg to 9.3 mg of mazdutide or a pharmaceutically acceptable salt thereof weekly for at least 40 weeks, preferably about 9 mg of mazdutide or a pharmaceutically acceptable salt thereof weekly for at least 40 weeks, and more preferably about 9 mg of mazdutide or a pharmaceutically acceptable salt thereof once a week for at least 40 weeks.

6. The pharmaceutical composition according to claim 1, wherein the administration is by injection, preferably by subcutaneous injection.

7. A pharmaceutical composition according to claim 1, comprising mazdutide or a pharmaceutically acceptable salt thereof, administered in a dosing schedule comprising a first dosing cycle, a second dosing cycle, and a third dosing cycle, wherein the dosing schedule comprises: (i) In the first administration cycle, approximately 3 mg of mazdutide or a pharmaceutically acceptable salt thereof is administered to the patient weekly for approximately 4 weeks. (ii) In the second administration cycle, approximately 6 mg of mazdutide or a pharmaceutically acceptable salt thereof is administered to the patient weekly for approximately 4 weeks, and (iii) In the third administration cycle, approximately 9 mg of mazdutide or a pharmaceutically acceptable salt thereof is administered to the patient weekly for 4 weeks or at least approximately 4 weeks.

8. The pharmaceutical composition according to claim 7, wherein approximately 9 mg of mazdutide or a pharmaceutically acceptable salt thereof is administered weekly for approximately 16 weeks or at least approximately 16 weeks.

9. The pharmaceutical composition according to claim 7, wherein approximately 9 mg of mazdutide or a pharmaceutically acceptable salt thereof is administered weekly for approximately 40 weeks or at least approximately 40 weeks.

10. The patient, (a) Obese and / or BMI ≥ 28.0 kg / m², (b) Obese and / or BMI ≥ 30.0 kg / m², (c) Overweight and / or 24 kg / m² ≤ BMI < 28.0 kg / m², The pharmaceutical composition according to claim 1.

11. The pharmaceutical composition according to claim 1, wherein the patient is overweight and / or the patient has at least one of the following: i) Increased appetite, unbearable hunger before meals, and increased food intake, ii) Complications of prediabetes, wherein the complications of prediabetes are selected from the group consisting of fasting blood glucose abnormalities and / or impaired glucose tolerance, hypertension, dyslipidemia, and fatty liver. iii) Complications with weight-bearing joint pain, and iv) Obesity-related dyspnea or obstructive sleep apnea syndrome.

12. The pharmaceutical composition according to claim 1, wherein the patient does not have type 1 or type 2 diabetes prior to treatment, and / or the patient does not have HbA1c ≥ 6.5% prior to treatment.

13. A pharmaceutical composition for preventing or treating obesity or overweight in human subjects, wherein mazdutide or a pharmaceutically acceptable salt thereof is administered in a dose of about 6 mg or about 9 mg.

14. The pharmaceutical composition according to claim 13, wherein about 6 mg or about 9 mg of mazdutide or a pharmaceutically acceptable salt thereof is administered weekly for about 4 weeks or at least about 4 weeks.

15. The pharmaceutical composition according to claim 13, wherein about 9 mg of mazdutide or a pharmaceutically acceptable salt thereof is administered weekly for at least 16 weeks or at least 40 weeks.

16. The patient: (a) Obese and / or BMI ≥ 28.0 kg / m², (b) Obese and / or BMI ≥ 30.0 kg / m², (c) Overweight and / or 24 kg / m² ≤ BMI < 28.0 kg / m², The pharmaceutical composition according to claim 13.

17. The pharmaceutical composition according to claim 13, wherein the patient is overweight and / or the patient has at least one of the following: i) Increased appetite, unbearable hunger before meals, and increased food intake, ii) Complications of prediabetes, wherein the complications of prediabetes are selected from the group consisting of fasting blood glucose abnormalities and / or impaired glucose tolerance, hypertension, dyslipidemia, and fatty liver. iii) Complications with weight-bearing joint pain, and iv) Obesity-related dyspnea or obstructive sleep apnea syndrome.

18. The pharmaceutical composition according to claim 13, wherein the patient does not have type 1 or type 2 diabetes prior to treatment, and / or the patient does not have HbA1c ≥ 6.5% prior to treatment.

19. Use of a target compound for producing the pharmaceutical composition according to any one of claims 1 to 18.

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