Semaglutide in medical therapies, including weight management

Abstract

The problem that this invention aims to solve is to provide a method for weight management for individuals who require weight management. [Solution] The present invention relates to a pharmaceutical product used for weight management of subjects requiring weight management, comprising semaglutide, wherein the semaglutide is administered subcutaneously at an amount of approximately 7.2 mg per week.

Description

[Technical Field]

[0001] The present invention relates to a method of medical therapy, including weight management such as obesity, comprising the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide. [Background technology]

[0002] Obesity is one of the most serious public health challenges worldwide, reaching epidemic rates in most countries around the globe. Obesity is associated with an increased risk of various comorbidities, including cardiovascular disease and premature death. Furthermore, obesity negatively impacts physical and mental health and reduces health-related quality of life. Obesity is also associated with reduced cardiac and respiratory fitness, which also increases the risk of cardiovascular disease and all-cause mortality.

[0003] Semaglutide is approved in many countries for weight management, including obesity (Wegovy®), administered subcutaneously once a week, with an initial dose of 0.25 mg, followed by dose escalations of 0.5 mg every four weeks, then 1.0 mg, then 1.7 mg, and finally 2.4 mg, with a recommended maintenance dose of 2.4 mg. The glucose-dependent insulinotropic polypeptide (GIP) receptor and GLP-1 receptor agonist tilzepatide is approved in many countries for weight management, including obesity (Zepbound®), administered subcutaneously, with an initial dose of 2.5 mg, followed by dose escalations of 2.5 mg every four weeks up to 5 mg, adjusted as needed to 7.5 mg, then 10 mg, and as needed to 12.5 mg, then 15 mg, with a recommended maintenance dose of 5 mg, 10 mg, or 15 mg, to reduce the risk of gastrointestinal adverse reactions. [Overview of the project] [Means for solving the problem]

[0004] In some embodiments, the present invention relates to a method for weight management of a subject who needs weight management, the method comprising subcutaneously administering to the subject semaglutide in an amount of about 7.2 mg per week. In some embodiments, the present invention is directed to a method for treating or reducing one or more risks selected from the group consisting of (i) cardiovascular (CV) diseases such as reducing the risk of major adverse cardiovascular events such as CV death, non-fatal myocardial infarction, and non-fatal stroke, (ii) metabolic dysfunction-associated steatohepatitis, and (iii) chronic kidney disease, in a human subject who needs it, the method comprising subcutaneously administering about 7.2 mg of semaglutide per week.

Brief Description of Drawings

[0005] [Figure 1] Figure 1 shows the weight loss observed in subjects co-administered cagrilintide and semaglutide. The vertical reference lines represent the first and last administrations of cagrilintide and semaglutide.

Modes for Carrying Out the Invention

[0006] The present disclosure provides a pharmaceutical composition comprising semaglutide or a pharmaceutically acceptable salt thereof.

[0007] The inventors have surprisingly found that once-weekly subcutaneous administration of 7.2 mg of semaglutide provides an improved benefit-risk profile in human subjects. Compared to 2.4 mg, once-weekly subcutaneous administration of 7.2 mg of semaglutide resulted in greater weight loss without increasing gastrointestinal adverse events such as nausea and vomiting to the same extent. The percentage of subjects discontinuing treatment was similar for once-weekly subcutaneous administration of 7.2 mg of semaglutide and 2.4 mg of semaglutide, as shown in the examples of the present disclosure.

[0008] To our surprise, the inventors found that direct dose escalation from weekly subcutaneous administration of semaglutide 2.4 mg to 7.2 mg was well tolerated. The dose escalation of 2.4 mg to 7.2 mg (3 doses) was significantly higher than the dose escalation steps from a single maintenance dose to the next dose in the case of approved weight management agents, including GLP-1 receptor agonists. As used in this disclosure, the term “maintenance dose” may refer, for example, to the dose approved for treatment after the dose escalation period. For tilzepatide, the dose escalation increase to 10 mg was 1.3 times (10 / 7.5), and the dose escalation increase to 15 mg was 1.2 times (15 / 12.5).

[0009] Subcutaneous administration of 7.2 mg of semaglutide once weekly resulted in significantly greater weight loss compared to 2.4 mg, as shown in the examples of this disclosure. In particular, in a significantly higher proportion of subjects, subcutaneous administration of 7.2 mg of semaglutide once weekly resulted in weight loss of at least 15%, at least 20%, and at least 25% compared to 2.4 mg as shown in the examples of this disclosure. Furthermore, in a significantly higher proportion of subjects, subcutaneous administration of 7.2 mg of semaglutide once weekly resulted in weight loss of 27 kg / m² compared to 2.4 mg, as shown in the examples of this disclosure. 2A BMI of less than 10% was achieved, i.e., the subject was no longer overweight or obese according to the International BMI classification. In some embodiments, the effects referred to herein are for subjects who are (i) obese or (ii) overweight and have at least one comorbidity, such as type 2 diabetes. In some embodiments, the effects referred to herein are for subjects who are obese. In some embodiments, the effects referred to herein are for subjects who are not diabetic, such as those who are not type 1 diabetes and those who are not type 2 diabetes. In some embodiments, the effects referred to herein are for subjects who are obese and not diabetic. In some embodiments, once-weekly subcutaneous administration of semaglutide 7.2 mg resulted in significantly greater weight loss in obese and non-diabetic subjects compared to 2.4 mg. In some embodiments, a significantly higher proportion of subjects achieved weight loss of at least 15%, at least 20%, and at least 25% with once-weekly subcutaneous administration of semaglutide 7.2 mg compared to 2.4 mg in obese and non-diabetic subjects. In some embodiments, a significantly higher proportion of subjects with obesity and no diabetes received 7.2 mg of semaglutide once weekly subcutaneously compared to 2.4 mg in subjects weighing 27 kg / m². 2 A BMI of less than 100% has been achieved, i.e., the patient is no longer overweight or obese according to the International BMI classification. In some embodiments, the present invention surprisingly provides a safe and tolerable medical therapy for weight management, including overweight and obesity, which provides increased weight loss. In some embodiments, the present invention surprisingly provides a safe and tolerable medical therapy for obesity which provides increased weight loss.

[0010] For both systolic and diastolic blood pressure, the reduction in blood pressure was remarkably large with weekly subcutaneous administration of 7.2 mg of semaglutide compared to 2.4 mg of semaglutide or placebo, as shown in the examples of this disclosure. In some embodiments, the present invention surprisingly provides a safe and well-tolerated medical therapy for weight management, including overweight and obesity.

[0011] Even more surprisingly, as shown in the examples of this disclosure, semaglutide containing 7.2 mg of semaglutide was found to reduce lean body volume compared to fat volume to less than expected.

[0012] In some embodiments, the present invention relates to a method for weight management for subjects requiring weight management, wherein the subject receives subcutaneous administration of approximately 7.2 mg of semaglutide per week. In some embodiments, weight management includes subcutaneous administration of approximately 7.2 mg of semaglutide once a week. In some embodiments, the present invention relates to a treatment for obesity or overweight, comprising subcutaneous administration of approximately 7.2 mg of semaglutide once a week to subjects requiring it. In some embodiments, the present invention relates to a treatment for obesity, comprising subcutaneous administration of approximately 7.2 mg of semaglutide once a week to subjects requiring it. In some embodiments, the present invention relates to a treatment for overweight, comprising subcutaneous administration of approximately 7.2 mg of semaglutide once a week to subjects requiring it. In some embodiments, the treatment for overweight and the subject further have at least one weight-related comorbidity.

[0013] In some embodiments, the present invention relates to a method for weight management in a human subject requiring it, comprising subcutaneous administration of about 7.2 mg of semaglutide per week, wherein semaglutide provides a weight loss of at least about 15%, for example, at least 18% or at least 20%. In some embodiments, the present invention relates to a method for the treatment of obesity or overweight, wherein, for the treatment of overweight, the subject may have at least one weight-related comorbidity. In some embodiments, the present invention relates to a method for the treatment of obesity or overweight, wherein the subcutaneous administration further comprises one or more dose-escalation steps of administration of up to about 2.4 mg of semaglutide per week prior to administration of about 7.2 mg of semaglutide per week, wherein, for the treatment of overweight, the subject may have at least one weight-related comorbidity. In some embodiments, the present invention relates to a method for treating obesity or overweight, wherein semaglutide is administered in the form of a pharmaceutical composition comprising semaglutide, the composition having a pH in the range of about 5.6 to about 9.0, and for the treatment of overweight, the subject may have at least one weight-related comorbidity. In some embodiments, the present invention relates to a method for treating obesity or overweight, the method does not involve the administration of cyclodextrin, and for the treatment of overweight, the subject may have at least one weight-related comorbidity.

[0014] In some embodiments, the present invention relates to a method for weight management in a human subject requiring it, comprising a subcutaneous administration of approximately 7.2 mg of semaglutide once weekly, wherein semaglutide provides a weight loss of at least about 15%, such as at least 18% or at least 20%. In some embodiments, the present invention relates to a method for the treatment of obesity or overweight, wherein, for the treatment of overweight, the subject may have at least one weight-related comorbidity. In some embodiments, the present invention relates to a method for the treatment of obesity or overweight, wherein the subcutaneous administration further comprises a weekly administration of up to approximately 2.4 mg of semaglutide, a weekly administration of approximately 7.2 mg of semaglutide, and one or more dose-escalation steps for the treatment of overweight, wherein the subject may have at least one weight-related comorbidity. In some embodiments, the present invention relates to a method for treating obesity or overweight, wherein semaglutide is administered in the form of a pharmaceutical composition comprising semaglutide, the composition having a pH in the range of about 5.6 to about 9.0, and for the treatment of overweight, the subject may have at least one weight-related comorbidity. In some embodiments, the present invention relates to a method for treating obesity or overweight, the method does not involve the administration of cyclodextrin, and for the treatment of overweight, the subject may have at least one weight-related comorbidity.

[0015] In some embodiments, the present invention relates to a method for treating or reducing cardiovascular disease in human subjects requiring the use of a subcutaneous dose of approximately 7.2 mg of semaglutide per week. In some embodiments, the present invention relates to a method for reducing the risk of major adverse cardiovascular events such as cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke in human subjects requiring the use of a subcutaneous dose of approximately 7.2 mg of semaglutide per week. In some embodiments, the present invention relates to a method for treating heart failure, such as heart failure with preserved ejection fraction, in human subjects requiring the treatment or reduction of the risk of heart failure. In some embodiments, heart failure is heart failure with preserved ejection fraction. In some embodiments, the present invention relates to a method for treating peripheral artery disease in human subjects requiring the use of a subcutaneous dose of approximately 7.2 mg of semaglutide per week.

[0016] In some embodiments, the present invention relates to a method for treating metabolic dysfunction-associated steatohepatitis (MASH) in human subjects requiring subcutaneous administration of approximately 7.2 mg of semaglutide per week. Metabolic dysfunction-associated steatohepatitis (MASH) is also known as non-alcoholic steatohepatitis (NASH).

[0017] In some embodiments, the present invention relates to a method for treating type 2 diabetes in subjects requiring weight management, wherein the subject is subcutaneously administered approximately 7.2 mg of semaglutide per week.

[0018] In some embodiments, the present invention relates to a method for treating Alzheimer's disease in a human subject requiring such treatment, comprising subcutaneous administration of approximately 7.2 mg of semaglutide per week. In some embodiments, Alzheimer's disease is early Alzheimer's disease.

[0019] In some embodiments, the present invention relates to a method for treating chronic kidney disease in human subjects requiring it, comprising subcutaneous administration of approximately 7.2 mg of semaglutide per week.

[0020] In some embodiments, as used in this disclosure, the term "treatment" refers to a medical therapy involving the administration of a specific active ingredient, such as semaglutide, in amounts and frequencies that produce a therapeutic effect that is preventive, palliative, symptomatic, and / or curative. In some embodiments, the treatment is symptomatic and / or curative. In some embodiments, the treatment is preventive, including preventing the worsening of a condition such as obesity.

[0021] The subjects are human beings, and may be obese or overweight. In some embodiments, the subjects are obese. In some embodiments, the subjects are overweight. In some embodiments, the subjects are overweight and have at least one weight-related comorbidity. In some embodiments, the weight-related comorbidity is selected from the group consisting of diabetes mellitus, cardiovascular disease, metabolic dysfunction-related steatohepatitis, alcoholic liver disease, and obstructive sleep apnea.

[0022] BMI (Body Mass Index) is calculated by dividing the subject's weight in kilograms (kg) and their height in square meters (m). 2 It is calculated by dividing by (). Unless otherwise stated, references to BMI in this disclosure are based on the International Classification used, for example, in the United States and Europe. In some embodiments, the subjects are those with a BMI of at least 30.

[0023] The term "obesity" refers to a minimum of 30 kg / m². 2 In this disclosure, a subject having a BMI of may be defined as such. In some embodiments, based on the Chinese classification, obesity is defined as having a BMI of at least 28 kg / m². 2 In this disclosure, a subject having a BMI of is defined as such. In some embodiments, based on the Japanese classification, obesity is defined as having a BMI of at least 25 kg / m². 2is defined in the present disclosure as a subject having a BMI of. In some embodiments, based on the Taiwan classification, obesity is at least 27 kg / m 2 is defined in the present disclosure as a subject having a BMI of.

[0024] The term "overweight" can be defined in the present disclosure as a subject having a BMI of at least 27 kg / m 2 . In some embodiments, based on the Chinese classification, overweight is at least 24 kg / m2 to less than 28 kg / m 2 such as at least 24 kg / m 2 is defined in the present disclosure as a subject having a BMI of. In some embodiments, based on the Taiwan classification, overweight is at least 24 kg / m2 to less than 27 kg / m 2 such as at least 24 kg / m 2 is defined in the present disclosure as a subject having a BMI of.

[0025] In some embodiments, the subject has a BMI of at least 30 kg / m 2 . The subject may have a BMI of at least 35 kg / m​​​​​​​​​​​​​​​​​​​​​​​The subjects may have a BMI of at least 30 kg / m² and a body weight of at least approximately 120 kg. 2 They may have a BMI of at least approximately 140 kg.

[0027] The subjects may be adults or children. The subjects may be adults. The subjects may be children. In some embodiments, the subjects are children (e.g., 5 to under 18 years old), such as adolescents (e.g., 12 to under 18 years old). For children, obesity is defined as at least 30 kg / m² for adults, as defined in Table 4 of Cole et al., BMJ. 2000 May 6;320(7244):1240 (doi:10.1136 / bmj.320.7244.1240). 2 It may be defined as a subject having a BMI corresponding to [a certain value]. The subject may be a child aged 12 years or older. The subject may be a child, and in the case of an adult, at least 30 kg / m². 2 It may also have a corresponding BMI.

[0028] The term “lean body” as used in this disclosure may also be defined as the total body volume minus total fat in the body portion being analyzed. For example, lean body volume may be the total body volume minus total fat volume. The term “total fat” as used in this disclosure may be defined as the sum of all fat in the body portion being analyzed, for example, from spine T9 to the knee. The term “visceral fat” as used in this disclosure may also be defined as fat located within the abdominal cavity, and therefore visceral fat includes periabdominal organs such as the liver, pancreas, and kidneys.

[0029] In some embodiments, the subject has diabetes, such as type 2 diabetes. In some embodiments, the subject has type 2 diabetes. In some embodiments, the subject has at least one weight-related comorbidity (such as dyslipidemia or hypertension). The subject may be overweight and have at least one weight-related comorbidity, such as dyslipidemia or hypertension. The subject has a weight of at least 27 kg / m². 2 The subjects may have a BMI and at least one weight-related comorbidity, such as dyslipidemia or hypertension. In some embodiments, the subjects are not classified as New York Heart Association (NYHA) Class IV.

[0030] In some embodiments, weight management is the treatment of overweight or obesity in human subjects who require it, and the subjects may have at least one weight-related comorbidity. The term “weight-related comorbidity” includes hyperglycemia, type 2 diabetes, hypertension, dyslipidemia, obstructive sleep apnea, metabolic dysfunction-related steatohepatitis, and / or cardiovascular disease. In some embodiments, weight management is the treatment of overweight in human subjects who require it, and the subjects may have at least one weight-related comorbidity. In some embodiments, weight management is the treatment of obesity in human subjects who require treatment for obesity, and the subjects may have at least one weight-related comorbidity. In some embodiments, weight management is supplemented by a calorie-reducing diet and increased physical activity. In some embodiments, weight management in subjects requiring weight management is supplemented by a calorie-reducing diet and increased physical activity, and the subjects are obese. In some embodiments, weight management in subjects requiring weight management is supplemented by a calorie-reducing diet and increased physical activity, and the subjects are overweight and have at least one weight-related comorbidity. In some embodiments, weight management in subjects requiring weight management is supplementary to a calorie-reducing diet and increased physical activity, and the subjects weigh at least 28 kg / m². 2 or at least 25 kg / m 2 For example, at least 30 kg / m 2The subject has a BMI of at least 24 kg / m². In some embodiments, weight management in subjects requiring weight management is supplemented by a reduced calorie diet and increased physical activity, and the subject has a BMI of at least 24 kg / m². 2 such as at least 27 kg / m³ 2 The patient has a BMI of [value missing] and at least one weight-related comorbidity.

[0031] In some embodiments, the method of the present invention provides weight loss for the subject.

[0032] In some embodiments, the weight loss is at least about 15%, such as at least about 18% or at least 20%. In some embodiments, semaglutide provides a weight loss of at least about 15%, such as at least 18% or at least 20%. In some embodiments, the weight loss is at least about 15%. In some embodiments, the weight loss is at least 18%. In some embodiments, the weight loss is at least 20%. In some embodiments, the weight loss is at least 25%.

[0033] In some embodiments, semaglutide provides a weight loss of at least about 15%, such as at least 18% or at least 20%. In some embodiments, about 7.2 mg of semaglutide per week provides a weight loss of at least about 15%, such as at least 18% or at least 20%. In some embodiments, about 7.2 mg of semaglutide administered for at least 52 weeks, such as at least 72 weeks including dose escalation, results in a weight loss of at least about 15%, such as at least 18% or at least 20%. In some embodiments, about 7.2 mg of semaglutide per week administered for at least 52 weeks provides a weight loss of at least about 15%, such as at least 18% or at least 20%. In some embodiments, about 7.2 mg of semaglutide per week administered for at least 72 weeks including dose escalation provides a weight loss of at least about 15%, such as at least 18% or at least 20%. In some embodiments, approximately 7.2 mg of semaglutide per week, administered for at least 52 weeks, provides a weight loss of at least approximately 15%. In some embodiments, approximately 7.2 mg of semaglutide per week, administered for at least 52 weeks, provides a weight loss of at least approximately 20%. In some embodiments, approximately 7.2 mg of semaglutide per week, administered for at least 52 weeks, provides a weight loss of at least approximately 25%. In some embodiments, the weight loss is at least approximately 15% after at least approximately 52 weeks of administration of approximately 7.2 mg of semaglutide. In some embodiments, the weight loss is at least 15% after at least approximately 52 weeks of administration of approximately 7.2 mg of semaglutide. In some embodiments, the weight loss is at least 18% after at least 52 weeks of administration of 7.2 mg of semaglutide. In some embodiments, weight loss is at least 20% after administration of about 7.2 mg of semaglutide for at least about 52 weeks. In some embodiments, weight loss is at least 25% after administration of about 7.2 mg of semaglutide for at least about 52 weeks. In some embodiments, weight loss is up to 75%.In some embodiments, weight loss is up to 75% after administration of approximately 7.2 mg of semaglutide for at least approximately 52 weeks.

[0034] In some embodiments, a larger proportion of subjects achieve at least a 20% weight loss with weekly administration of 7.2 mg of semaglutide compared to weekly administration of 2.4 mg of semaglutide. In some embodiments, at least 45%, e.g., about 50%, of subjects achieve at least a 20% weight loss with 7.2 mg of semaglutide. In some embodiments, at least 45%, e.g., about 50%, of subjects achieve at least a 20% weight loss with weekly administration of 7.2 mg of semaglutide. In some embodiments, a larger proportion of subjects achieve at least a 25% weight loss with weekly administration of about 7.2 mg of semaglutide compared to weekly administration of 2.4 mg of semaglutide. In some embodiments, at least 25%, e.g., at least 30%, e.g., about 33%, of subjects achieve at least a 25% weight loss with about 7.2 mg of semaglutide. In some embodiments, at least 30% of the subjects, for example about 33%, achieve at least a 25% weight loss with about 7.2 mg of semaglutide once a week. In some embodiments, a larger proportion of the subjects achieve a weight loss of 27 kg / m². 2 A BMI of less than 27 kg / m² is achieved with a dose of approximately 7.2 mg of semaglutide per week, compared to approximately 2.4 mg of semaglutide per week. In some embodiments, a larger proportion of subjects achieved a BMI of 27 kg / m² with a dose of approximately 7.2 mg of semaglutide per week. 2 A BMI of less than 27 kg / m² was obtained with a dose of 7.2 mg of semaglutide once weekly, compared with a dose of 2.4 mg of semaglutide once weekly. In some embodiments, a larger proportion of subjects achieved a BMI of 27 kg / m² with a dose of 7.2 mg of semaglutide once weekly. 2 A BMI of less than 27 kg / m2 is obtained. In some embodiments, at least about 25% of the subjects, e.g., about 27%, obtain a BMI of less than 27 kg / m2 with 7.2 mg of semaglutide. In some embodiments, a larger proportion of the subjects obtain a BMI of less than 27 kg / m2 with a dose of about 7.2 mg of semaglutide per week compared to about 2.4 mg of semaglutide per week. 2A BMI of less than 27 kg / m² was obtained with a dose of 7.2 mg of semaglutide once weekly, compared with a dose of 2.4 mg of semaglutide once weekly. In some embodiments, a larger proportion of subjects achieved a BMI of 27 kg / m² with a dose of 7.2 mg of semaglutide once weekly. 2 Achieve a BMI of less than the following.

[0035] In some embodiments, the method provides a reduction of fat-free weight compared to total fat by less than 20%, for example, less than 18%, for example, less than 17%, or less than 16%. In some embodiments, the method provides a reduction of fat-free weight compared to total fat by 16.5% or less. In some embodiments, the method provides a reduction of fat-free weight compared to total fat by 16% or less. In some embodiments, the method provides a reduction of fat-free weight compared to total fat by 15.5% or less. In some embodiments, the method provides a reduction of fat-free weight compared to total fat by 15% or less. In some embodiments, the method provides a reduction of fat-free weight compared to total fat by about 10% to about 20%.

[0036] In some embodiments, a larger proportion of subjects obtain a waist-to-height ratio of less than 0.50 with a weekly administration of 7.2 mg of semaglutide compared to a weekly administration of 2.4 mg of semaglutide. In some embodiments, the method provides a waist-to-height ratio of less than 0.50 in at least about 10% of subjects. In some embodiments, at least 10% of subjects, e.g., at least about 12% or at least about 14%, obtain a waist-to-height ratio of less than 0.50 with a weekly administration of 7.2 mg of semaglutide. The waist-to-height ratio can be calculated by dividing the subject's waist circumference by its height.

[0037] In some embodiments, the method is tolerable to the subjects. In some embodiments, the proportion of subjects discontinuing administration of about 7.2 mg of semaglutide is less than about 15%. In some embodiments, the proportion of subjects discontinuing administration of about 7.2 mg of semaglutide is between about 8% and about 15%. In some embodiments, the proportion of subjects discontinuing administration of about 7.2 mg of semaglutide within at least about 52 weeks is less than about 15%. In some embodiments, the proportion of subjects discontinuing administration of about 7.2 mg of semaglutide at least about 52 weeks after the initial dose escalation, where dose escalation is as defined herein. In some embodiments, the proportion of subjects discontinuing administration of about 7.2 mg of semaglutide within at least about 52 weeks after the initial dose escalation of up to about 2.4 mg of semaglutide once weekly is less than 15%. In some embodiments, the proportion of subjects discontinuing administration of approximately 7.2 mg of semaglutide within up to approximately 72 weeks from the initial semaglutide dose escalation step, such as an initial semaglutide dose escalation step of 0.25 mg semaglutide once weekly, is less than 15%. In some embodiments, the proportion of subjects discontinuing administration of approximately 7.2 mg of semaglutide within up to approximately 72 weeks from the initial semaglutide dose escalation step, such as an initial semaglutide dose escalation step of 0.25 mg semaglutide once weekly, is less than 15%, and the method includes dose escalation of up to approximately 2.4 mg of semaglutide once weekly. In some embodiments, the proportion of subjects discontinuing administration of approximately 7.2 mg of semaglutide is less than 12%. In some embodiments, the proportion of subjects discontinuing administration of approximately 7.2 mg of semaglutide within at least approximately 52 weeks is less than 12%. In some embodiments, the proportion of subjects discontinuing administration of approximately 7.2 mg of semaglutide within at least approximately 52 weeks of the initial dose escalation, where dose escalation is as defined herein. In some embodiments, the proportion of subjects discontinuing administration of approximately 7.2 mg of semaglutide within at least approximately 52 weeks after an initial dose escalation of up to approximately 2.4 mg of semaglutide once weekly is less than 12%.In some embodiments, less than 12% of subjects discontinue administration of approximately 7.2 mg of semaglutide within approximately 72 weeks from the initial semaglutide dose escalation step, such as the initial semaglutide dose escalation step of 0.25 mg semaglutide once weekly. In some embodiments, less than 12% of subjects discontinue administration of approximately 7.2 mg of semaglutide within approximately 72 weeks from the initial semaglutide dose escalation step, such as the initial semaglutide dose escalation step of 0.25 mg semaglutide once weekly, and the method includes dose escalation of up to approximately 2.4 mg of semaglutide once weekly. In some embodiments, “discontinuation” is permanent discontinuation, such as discontinuation for at least 4 weeks or at least 8 weeks. In some embodiments, less than approximately 15% of subjects discontinue administration of approximately 7.2 mg of semaglutide, and semaglutide results in a weight loss of at least approximately 15%. In some embodiments, the proportion of subjects experiencing at least one gastrointestinal adverse event is about 65% to about 75%. In some embodiments, the proportion of subjects experiencing at least one gastrointestinal adverse event is about 65% to about 75% during administration of about 7.2 mg of semaglutide within about 52 weeks. In some embodiments, the proportion of subjects experiencing at least one gastrointestinal adverse event during administration of about 7.2 mg of semaglutide within about 52 weeks is about 71%. In some embodiments, the proportion of subjects experiencing at least one gastrointestinal adverse event is about 71% during administration of about 7.2 mg of semaglutide within about 72 weeks, including dose escalation. In some embodiments, the proportion of subjects experiencing at least one gastrointestinal adverse event is about 65% to about 75%. In some embodiments, the proportion of subjects experiencing at least one gastrointestinal adverse event is about 35% to about 50%. In some embodiments, the proportion of subjects experiencing at least one gastrointestinal adverse event is about 40% to about 48%. In some embodiments, the proportion of subjects experiencing at least one gastrointestinal adverse event is approximately 44%.

[0038] In some embodiments, the waist circumference of the subject is reduced.

[0039] In some embodiments, the target blood pressure decreases. In some embodiments, the target diastolic and / or systolic blood pressure is reduced. In some embodiments, both the target diastolic and systolic blood pressure are reduced.

[0040] In some embodiments, the present invention relates to semaglutide for use in weight management, including subcutaneous administration of approximately 7.2 mg of semaglutide per week to human subjects, such as in the treatment of obesity or overweight.

[0041] In some embodiments, the present invention relates to the use of semaglutide in the manufacture of pharmaceuticals for use in weight management, such as the treatment of obesity or overweight, including subcutaneous administration of about 7.2 mg of semaglutide per week to human subjects, such as the treatment of obesity or overweight.

[0042] In some embodiments, the present invention relates to a pharmaceutical composition comprising semaglutide formulated for subcutaneous administration of approximately 7.2 mg of semaglutide per week. In some embodiments, the present invention relates to a pharmaceutical composition comprising semaglutide formulated for subcutaneous administration of approximately 7.2 mg of semaglutide per week to human subjects having an overweight or obese body.

[0043] In some embodiments, the present invention relates to a kit comprising semaglutide or a pharmaceutically acceptable salt thereof. In some embodiments, the present invention relates to a kit comprising semaglutide and instructions for use, wherein the semaglutide is for subcutaneous administration at a dose of approximately 7.2 semaglutide per week. In some embodiments, the present invention relates to a kit comprising semaglutide and instructions for use, wherein the semaglutide is for subcutaneous administration at a dose of approximately 7.2 semaglutide per week, and the semaglutide is contained in a vial. In some embodiments, the present invention relates to a kit comprising semaglutide and instructions for use, wherein the semaglutide is for subcutaneous administration at a dose of approximately 7.2 semaglutide per week, and the semaglutide is contained in an injection device.

[0044] Semaglutide The method of the present invention comprises the GLP-1 receptor agonist semaglutide. Semaglutide is N-epsilon26-[2-(2-{2-[2-(2-{2-[(S)-4-carboxy-4-(17-carboxyheptadecanoyl-amino)butyrylamino]ethoxy}ethoxy)acetylamino]ethoxy}ethoxy)acetyl][Aib8,Arg34]GLP-1-(7-37), which can be prepared as described in Example 4 of WO2006 / 097537, the entirety of which is incorporated by reference. Semaglutide may also be in the form of a salt, such as a pharmaceutically acceptable salt, preferably. In some embodiments, as used in this disclosure, the term “GLP-1 receptor agonist” refers to any compound, including peptides and non-peptide compounds, which, as determined by methods known in the art, have a potency of less than 100 nM (EC2). 50 See WO98 / 08871, for example, which binds to the human GLP-1 receptor and whose entire contents are incorporated by reference. In some embodiments, a method for identifying a GLP-1 receptor agonist is described in WO93 / 19175, whose contents are incorporated by reference.

[0045] In some embodiments, semaglutide is the sole active ingredient administered by the method of the present invention. In some embodiments, the method of the present invention includes administering one or more additional active ingredients that are not GLP-1 receptor agonists to the target.

[0046] Administration regimen Semaglutide is administered by subcutaneous injection. In some embodiments, semaglutide is administered by subcutaneous injection. In some embodiments, semaglutide is contained in a vial. In some embodiments, semaglutide is loaded into an injection device. In some embodiments, semaglutide is administered via an injection device. In some embodiments, semaglutide may be administered using a pen-type syringe, such as a 3 ml disposable pen-type syringe.

[0047] In some embodiments, semaglutide is administered at a dose of approximately 7.2 mg per week. In some embodiments, semaglutide is administered at a dose of approximately 7.2 mg once per week. In some embodiments, semaglutide is administered at a dose of 7.2 mg per week.

[0048] In some embodiments, semaglutide is administered once a week. In some embodiments, semaglutide is administered once a week in an amount of approximately 7.2 mg of semaglutide. In some embodiments, semaglutide is administered once a week in an amount of 7.2 mg of semaglutide.

[0049] In some embodiments, semaglutide is administered in a fixed dose, with or without dose escalation, rather than a body weight-based dose. This fixed dose (e.g., approximately 7.2 mg of semaglutide) is applied to different control groups (changes in body weight, sex, disease severity, BMI, etc.) without individual dose adjustments. This simplifies the treatment regimen and improves patient compliance.

[0050] In some embodiments, semaglutide is administered for at least 24 weeks. Semaglutide may be administered for at least 32 weeks. Semaglutide may be administered for at least 40 weeks. Semaglutide may be administered for at least about 52 weeks. Semaglutide may be administered for at least about 72 weeks. Semaglutide may be administered for about 72 weeks. Semaglutide may be administered for at least about 72 weeks from the initial semaglutide dose escalation step. Semaglutide may be administered for up to about 72 weeks from the initial semaglutide dose escalation step. Semaglutide may be administered for at least about 72 weeks, including dose escalation. Semaglutide may be administered for about 72 weeks, including dose escalation. Semaglutide may be administered at a dose of about 7.2 mg per week for at least about 52 weeks.

[0051] In some embodiments, semaglutide is administered once daily or less frequently, such as once daily or once weekly. In some embodiments, the GLP-1 receptor agonist is administered at any time of day. In some embodiments, the method of the present invention is continued for at least about 4 weeks, such as at least about 5 weeks.

[0052] In some embodiments, the method according to the present invention is for chronic management. In some embodiments, the term “chronic management,” as used in this disclosure, means continuing administration of semaglutide according to the method of the present invention for a long period of time, such as at least one year. In some embodiments, the term “chronic management,” as used in this disclosure, means continuing administration of semaglutide according to the method of the present invention for at least five years, such as at least ten years. In some embodiments, the term “chronic management,” as used in this disclosure, means continuing administration of semaglutide according to the method of the present invention for at least fifteen years or at least twenty years. In some embodiments, the term “chronic management,” as used in this disclosure, means continuing administration of semaglutide according to the method of the present invention for the remainder of the subject's life. In some embodiments, the method according to the present invention is continued for at least about 48 weeks. In some embodiments, chronic management includes, for example, administration of semaglutide in an amount and frequency sufficient to treat obesity, as specified herein.

[0053] In some embodiments, semaglutide is the only GLP-1 receptor agonist administered by the method of the present invention. In some embodiments, semaglutide is the only active ingredient administered by the method of the present invention. In some embodiments, the method of the present invention includes administering one or more additional active ingredients that are not GLP-1 receptor agonists to the target.

[0054] Dosage gradual increase Administration of semaglutide may be initiated via dose escalation, i.e., starting with a dose lower than the therapeutic dose and gradually increasing over time toward the therapeutic dose. Dose escalation may help avoid one or more undesirable side effects. As used in this disclosure, the term “therapeutic dose” refers to the dose of semaglutide (i.e., the amount and frequency of administration). In some embodiments, the therapeutic dose produces a therapeutic effect in the referenced medical indication. In some embodiments, the method of the present invention comprises the first step of dose escalation, in which the subject is (i) administered a dose of semaglutide in the range of about one-tenth to half of the therapeutic dose, and then (ii) administered every 2 to 6 weeks, such as every 2 weeks, every 4 weeks, every 5 weeks, etc., and the dose is increased by 1.5 to 2.5 times, such as about 2 times, up to the therapeutic dose. In some embodiments, the method of the present invention comprises an initial step of dose escalation via parenteral administration, in which the subject is (i) a dose of semaglutide within the range of about 0.2 to 0.5 mg of semaglutide per week, for example, 0.35 mg of semaglutide per week, and then (ii) administered every 2 to 6 weeks, such as every 4 weeks, the dose is increased by 1.5 to 2.5 times, such as about 2 times, up to the therapeutic dose. In some embodiments, unless otherwise specified, the amount and / or frequency of administration of semaglutide described herein refers to the therapeutic dose. In some embodiments, the method of the present invention comprises dose escalation such as further dose escalation from about 2.4 mg of semaglutide per week to about 7.2 mg of semaglutide per week. In some embodiments, the therapeutic dose for subcutaneous administration is about 7.2 mg of semaglutide per week. In some embodiments, the therapeutic dose is about 2.4 mg of semaglutide per week.

[0055] In some embodiments, subcutaneous administration further comprises one or more dose-escalation steps of semaglutide up to about 2.4 mg per week, followed by a dose of semaglutide up to about 7.2 mg per week. In some embodiments, subcutaneous administration further comprises one or more dose-escalation steps of semaglutide from about 0.25 mg to about 2.4 mg per week, followed by a dose of semaglutide up to about 7.2 mg per week. In some embodiments, subcutaneous administration comprises a dose-escalation step of semaglutide up to about 2.4 mg per week, followed by a dose of semaglutide up to about 7.2 mg per week. In some embodiments, the method further comprises one or more dose-escalation steps of semaglutide up to about 2.4 mg per week before administering about 7.2 mg per week. In some embodiments, administration comprises a dose-escalation step of semaglutide up to about 2.4 mg per week before administering about 7.2 mg per week. In some embodiments, subcutaneous administration includes a dose escalation step for up to about 20 weeks, for example, about 20 weeks. In some embodiments, subcutaneous administration includes a dose escalation step for up to about 20 weeks with doses of about 2.4 mg of semaglutide per week or less, followed by a dose of about 7.2 mg of semaglutide per week. In some embodiments, subcutaneous administration includes doses of about 0.25 mg of semaglutide per week, about 0.5 mg of semaglutide per week, about 1.0 mg of semaglutide per week, about 1.7 mg of semaglutide per week, about 2.4 mg of semaglutide per week, followed by a dose of about 7.2 mg of semaglutide per week, every four weeks. In some embodiments, the method includes a dose escalation step of about 2.4 mg of semaglutide per week one week before the first dose of about 7.2 mg of semaglutide per week. In some embodiments, the method includes a dose escalation step of 2.4 mg of semaglutide once weekly, one week before a first dose of 7.2 mg of semaglutide once weekly. In some embodiments, the method includes a dose escalation step of weekly semaglutide administration in amounts of approximately (i) 0.25 mg to (ii) 0.5 mg to (iii) 1.0 mg to (iv) 1.7 mg to (v) 2.4 mg, before administering approximately 7.2 mg of semaglutide per week.In some embodiments, the method includes a dose escalation step starting with weekly administration of semaglutide in amounts of approximately (i) 0.25 mg to (ii) 0.5 mg to (iii) 1.0 mg to (iv) 1.7 mg to (v) 2.4 mg, before administering approximately 7.2 mg of semaglutide once a week. In some embodiments, the method includes a dose escalation step starting with weekly semaglutide administration in amounts of approximately (i) 0.25 mg to (ii) 0.5 mg to (iii) 1.0 mg to (iv) 1.7 mg to (v) 2.4 mg, every four weeks, before administering approximately 7.2 mg of semaglutide once a week. In some embodiments, the method includes a dose escalation step every four weeks from the weekly administration of semaglutide, with doses of (i) 0.25 mg to (ii) 0.5 mg to (iii) 1.0 mg to (iv) 1.7 mg to (v) 2.4 mg, before administering 7.2 mg of semaglutide once weekly.

[0056] In some embodiments, the present invention provides pharmaceutically acceptable combinations comprising 1) a first dose containing about 0.25 mg of semaglutide, and / or 2) a second dose containing about 0.5 mg of semaglutide, 3) and / or a third dose containing about 1.0 mg of semaglutide, 4) and / or a fourth dose containing about 1.7 mg of semaglutide, 5) and / or a fifth dose containing about 2.4 mg of semaglutide, and 6) a sixth dose containing about 7.2 mg of semaglutide.

[0057] In some embodiments, each dose is escalated every four weeks from a weekly dose of semaglutide, in amounts of (i) 0.25 mg to (ii) 0.5 mg to (iii) 1.0 mg to (iv) 1.7 mg to (v) 2.4 mg, before a weekly dose of 7.2 mg of semaglutide. In some embodiments, each dose comprises one to four weekly doses, preferably one weekly dose, or preferably four weekly doses.

[0058] In some embodiments, one or more doses of semaglutide are administered once a week to obtain 7.2 mg of semaglutide once a week. In some embodiments, 7.2 mg of semaglutide is administered once a week by administering one or more doses of semaglutide that, in combination, result in 7.2 mg of semaglutide once a week. In some embodiments, one or more doses of semaglutide may be any combination that results in 7.2 mg of semaglutide and are not limited to, for example, three doses of 2.4 mg of semaglutide. In some embodiments, 2.4 mg of semaglutide is administered three times consecutively, immediately following each other within a time interval such as, for example, 1 to 100 minutes, or for example, 1 to 5 minutes.

[0059] Other active ingredients In some embodiments, the method of the present invention includes the administration of one or more other active ingredients.

[0060] In some embodiments, the methods of the present invention further include the administration of an amyrin receptor agonist. Amyrin receptor agonists can bind to and activate the calcitonin receptor (CTR) and / or amyrin receptor (AMYR). AMYRs consist of a heterodimer of the calcitonin receptor (CTR) and two components of one of three receptor activity-modifying proteins (RAMP1-3), resulting in three possible complexes, AMYR1-3. "Amyrin receptor agonist" may be defined in this disclosure as a chemical substance that can bind to and activate the amyrin receptor, i.e., is "effective" on the amyrin receptor. In the context of the present invention, an amyrin receptor agonist can bind to and activate at least amyrin receptor 3 (AMYR3). Amyrin receptor agonists may also be capable of activating the calcitonin receptor, amyrin receptor 1 (AMYR1), and / or amyrin receptor 2 (AMYR2). The in vitro potency of amyrin receptor agonists against amyrin receptor 3 can be measured as described in assay 2 of WO2022 / 129526. The potency of the compound is measured by its EC 50 It may be described by value, EC 50This represents the concentration of the compound at which 50% of its maximum effect is observed. EC 50 The lower the value, the more potent the compound. When tested as described in Assay 2 of WO2022 / 129526, the amyrin receptor agonists disclosed herein have an EC of less than 300 pM, e.g., less than 200 pM, e.g., less than 150 pM, preferably less than 100 pM, e.g., less than 75 pM, preferably less than 50 pM, e.g., less than 40 pM, e.g., less than 30 pM, e.g., less than 20 pM, e.g., less than 10 pM. 50 It may also have a value.

[0061] Amyrin receptor agonists may be caglirintide, or a biologically active metabolite or degradation product of caglirintide. In some embodiments, the methods of the present invention further include the administration of caglirintide. Caglirintide, also known as AM833, is the compound of Example 53 of WO2012 / 168432: N-alpha-[(S)-4-carboxy-4-(19-carboxynonadecanoylamino)butyryl]-[Glu14,Arg17,Pro37]-pramlintide. Caglirintide may be prepared as described on pages 153-155 of WO2012 / 168432. Caglirintide may also be in the form of a salt, such as a pharmaceutically acceptable salt. Biologically active metabolites or degradation products of caglirintide may have an aspartate (Asp) at position 21 or 22. The biologically active metabolites or degradation products of caglirintide may have an iso-aspartate (iso-Asp) at position 21 or 22. When the potency of caglirintide was tested using the procedure described in Assay 2 of WO2022129526, caglirintide was found to have an EC of approximately 11 pM. 50 It had a value (WO2022 / 129526, Tables 4b and 4c).

[0062] In some embodiments, the method further includes the administration of caglilintide. In some embodiments, caglilintide is administered simultaneously with or sequentially with semaglutide. In some embodiments, caglilintide is administered subcutaneously. In some embodiments, semaglutide and caglilintide are administered subcutaneously. In some embodiments, caglilintide is administered subcutaneously. In some embodiments, semaglutide and caglilintide are administered subcutaneously.

[0063] In some embodiments, caglilintide is administered at a dose of approximately 0.25 to 16 mg per week. In some embodiments, caglilintide is administered at a dose of approximately 0.25 to 9 mg per week. In some embodiments, caglilintide is administered at a dose of approximately 0.25 to 4.5 mg per week. In some embodiments, caglilintide is administered at a dose of approximately 0.25 to 3.6 mg per week. In some embodiments, caglilintide is administered at a dose of approximately 0.25 to 2.4 mg per week. In some embodiments, caglilintide is administered at a dose of approximately 0.25 mg per week. In some embodiments, caglilintide is administered at a dose of approximately 0.5 mg per week. In some embodiments, caglilintide is administered at a dose of approximately 1.0 mg per week. In some embodiments, caglilintide is administered at a dose of approximately 1.7 mg per week. In some embodiments, caglilintide is administered at a dose of approximately 2.4 mg per week. In some embodiments, caglilintide is administered at a dose of approximately 3.6 mg per week. In some embodiments, caglilintide is administered once a week. In some embodiments, caglilintide is administered once a week at a dose of approximately 0.25 to 16 mg. In some embodiments, caglilintide is administered once a week at a dose of approximately 0.25 mg. In some embodiments, caglilintide is administered once a week at a dose of approximately 0.5 mg. In some embodiments, caglilintide is administered once a week at a dose of approximately 1.0 mg. In some embodiments, caglilintide is administered once a week at a dose of approximately 1.7 mg. In some embodiments, caglilintide is administered once a week at a dose of approximately 2.4 mg. In some embodiments, caglilintide is administered once a week at a dose of approximately 3.6 mg.

[0064] In some embodiments, kaglirintide is administered in the form of a pharmaceutical composition comprising kaglirintide and one or more excipients. In some embodiments, kaglirintide is administered in the form of a pharmaceutical composition comprising kaglirintide, semaglutide, and one or more excipients. In some embodiments, semaglutide is administered in the form of a pharmaceutical composition comprising kaglirintide, semaglutide, and one or more excipients. In some embodiments, the pharmaceutical composition comprising kaglirintide is a solution. In some embodiments, the pharmaceutical composition comprising kaglirintide is an aqueous solution. In some embodiments, the pharmaceutical composition comprising kaglirintide and semaglutide has a pH in the range of 5.6 to 6.0. In some embodiments, the pharmaceutical composition comprising kaglirintide and semaglutide has a pH in the range of 5.8 to 6.2. In some embodiments, the pharmaceutical composition comprising kaglirintide has a pH of about 3.5 to 4.5, for example, pH 4.0. In some embodiments, the pharmaceutical composition comprising kaglirintide includes a buffer. In some embodiments, the pharmaceutical composition containing kaglirintide contains glutamic acid, glutamic acid, lactate, lactic acid, acetic acid, or an acetic acid-based buffer. In some embodiments, the pharmaceutical formulation containing kaglirintide contains glutamic acid or a glutamate-based buffer. In some embodiments, the pharmaceutical formulation containing kaglirintide contains lactate or a lactate-based buffer. In some embodiments, the pharmaceutical formulation containing kaglirintide contains acetate or an acetic acid-based buffer.

[0065] In some embodiments, the administration of caglilintide further comprises one or more dose escalation steps, which may be as defined herein for semaglutide. In the dose escalation, the ratio of caglilintide to semaglutide may be about 1:1. Caglilintide and semaglutide may be administered in an initial dose escalation step of 0.25 mg per week, followed by further dose escalation steps of 0.5 mg, 1.0 mg, 1.7 mg, and 2.4 mg per week. Caglilintide and semaglutide may be administered once weekly in an initial dose escalation step of 0.25 mg, followed by further dose escalation steps of 0.5 mg, 1.0 mg, 1.7 mg, and 2.4 mg.

[0066] In dose escalation, the ratio of amyrin receptor agonist to GLP-1 receptor agonist may be 1:1 to 1:7. After dose escalation, the ratio of caglilintide to semaglutide may be 1:1 to 1:7. In some embodiments, semaglutide is administered subcutaneously at a maintenance dose of approximately 7.2 mg per week, and caglilintide is administered subcutaneously at a maintenance dose of approximately 2.4 mg per week.

[0067] The dose of caglilintide may be approximately 0.25 mg, and the dose of semaglutide may be approximately 0.25 mg. The dose of caglilintide may be approximately 0.5 mg, and the dose of semaglutide may be approximately 0.5 mg. The dose of caglilintide may be approximately 1.0 mg, and the dose of semaglutide may be approximately 1.0 mg. The dose of caglilintide may be approximately 1.7 mg, and the dose of semaglutide may be approximately 1.7 mg. The dose of caglilintide may be approximately 2.4 mg, and the dose of semaglutide may be approximately 2.4 mg. The dose of caglilintide may be approximately 2.4 mg, and the dose of semaglutide may be approximately 6.0 mg.

[0068] The maintenance dose of caglirintide may be approximately 2.4 mg, and the maintenance dose of semaglutide may be approximately 7.2 mg. The maintenance dose of caglirintide may be approximately 2.4 mg, and the maintenance dose of semaglutide may be approximately 6.0 mg. The maintenance dose of caglirintide may be approximately 2.4 mg, and the maintenance dose of semaglutide may be approximately 6.9 mg. The maintenance dose of caglirintide may be approximately 2.4 mg, and the maintenance dose of semaglutide may be approximately 8.0 mg.

[0069] In some embodiments, the present invention relates to a method for weight management in a human subject requiring it, comprising subcutaneous administration of approximately 7.2 mg of semaglutide per week, wherein semaglutide provides a weight loss of at least about 15%, such as at least 18% or at least 20%, and the method further comprises subcutaneous administration of approximately 0.25–16 mg of caglilintide per week. In some embodiments, the present invention relates to a method for the treatment of obesity or overweight, wherein for the treatment of overweight, the subject may have at least one weight-related comorbidity, and the method further comprises subcutaneous administration of approximately 0.25–16 mg of caglilintide per week. In some embodiments, the present invention relates to a method for the treatment of obesity or overweight. The subcutaneous administration further comprises one or more dose escalation steps of administering a maximum of approximately 2.4 mg of semaglutide per week, prior to administering approximately 7.2 mg of semaglutide per week. For the treatment of overweight, the subject may have at least one weight-related comorbidity, and the method further comprises subcutaneous administration of approximately 0.25 to 16 mg of caglilintide per week. In some embodiments, the present invention relates to a method for the treatment of obesity or overweight, in which semaglutide is administered in the form of a pharmaceutical composition comprising semaglutide, the composition having a pH in the range of approximately 5.6 to approximately 9.0, and for the treatment of overweight, the subject may have at least one weight-related comorbidity, and the method further comprises subcutaneous administration of approximately 0.25 to 16 mg of caglilintide per week. In some embodiments, the present invention relates to a method for the treatment of obesity or overweight, the method does not involve the administration of cyclodextrin, and for the treatment of overweight, the subject may have at least one weight-related comorbidity, the method further comprises subcutaneous administration of approximately 0.25 to 16 mg of caglilintide per week.

[0070] In some embodiments, the present invention relates to a method for weight management in a human subject requiring it, comprising a subcutaneous administration of approximately 7.2 mg of semaglutide once weekly, wherein semaglutide provides a weight loss of at least about 15%, such as at least 18% or at least 20%, and the method further comprises a subcutaneous administration of approximately 0.25–16 mg of caglirintide once weekly. In some embodiments, the present invention relates to a method for the treatment of obesity or overweight, wherein for the treatment of overweight, the subject may have at least one weight-related comorbidity, and the method further comprises a subcutaneous administration of approximately 0.25–16 mg of caglirintide once weekly. In some embodiments, the present invention relates to a method for the treatment of obesity or overweight. The subcutaneous administration further comprises one or more dose-escalation steps of administering semaglutide up to approximately 2.4 mg per week, prior to administering approximately 7.2 mg per week, for the treatment of overweight, the subject may have at least one weight-related comorbidity, and the method further comprises subcutaneous administration of approximately 0.25 to 16 mg of caglilintide once weekly. In some embodiments, the present invention relates to a method for the treatment of obesity or overweight, where semaglutide is administered in the form of a pharmaceutical composition comprising semaglutide, the composition having a pH in the range of approximately 5.6 to approximately 9.0, for the treatment of overweight, the subject may have at least one weight-related comorbidity, and the method further comprises subcutaneous administration of approximately 0.25 to 16 mg of caglilintide once weekly. In some embodiments, the present invention relates to a method for the treatment of obesity or overweight, the method does not involve the administration of cyclodextrin, and for the treatment of overweight, the subject may have at least one weight-related comorbidity, the method further comprises subcutaneous administration of approximately 0.25 to 16 mg of caglilintide once a week.

[0071] In some embodiments, the method of the present invention involves administering one or more additional active ingredients that are not GLP-1 receptor agonists to a target.

[0072] Pharmaceutical composition In the methods of the present invention, semaglutide may be administered in the form of a pharmaceutical composition, which is also referred to herein as a composition. Furthermore, in such embodiments, the pharmaceutically active ingredient is semaglutide. In some embodiments, the pharmaceutical composition comprises semaglutide and one or more excipients. In some embodiments, the pharmaceutical composition essentially consists of semaglutide and one or more excipients. In some embodiments, the pharmaceutical composition consists of semaglutide and one or more excipients. In some embodiments, the methods of the present disclosure include administering a pharmaceutical composition comprising semaglutide and one or more excipients.

[0073] Semaglutide may be administered in the form of a pharmaceutical composition described in WO2019 / 038412. Semaglutide may be administered in the form of a pharmaceutical composition described in WO2021 / 144477.

[0074] The pharmaceutical composition may contain semaglutide at a concentration of 0.1 mg / mL to 100 mg / mL. In some embodiments, the pharmaceutical composition contains semaglutide at a concentration of 0.01 to 50 mg / mL, or 0.01 to 20 mg / mL, or 0.01 to 10 mg / mL. In some embodiments, the pharmaceutical composition contains semaglutide at a concentration of 0.1 to 20 mg / mL. The concentration of semaglutide in the pharmaceutical formulation may be about 0.25 mg / mL to about 22 mg / mL.

[0075] In some embodiments, the pharmaceutical composition comprises a unit dosage form of semaglutide. One unit dosage form may contain a once-weekly dose. In some embodiments, a single weekly dose is up to 7.2 mg of semaglutide, for example, about 6.0 mg to about 7.2 mg of semaglutide, for example, about 7.2 mg of semaglutide. In some embodiments, the pharmaceutical composition comprises one to four unit dosage forms of semaglutide. In some embodiments, the pharmaceutical composition comprises about 7.2 to 28.8 mg of semaglutide, preferably about 7.2 mg or about 28.8 mg of semaglutide, and more preferably about 7.2 mg of semaglutide. In some embodiments, the pharmaceutical composition is contained in an injection device or vial.

[0076] In some embodiments, during the dose escalation process, one unit dosage form of semaglutide contains (i) 0.25 mg, (ii) 0.5 mg, (iii) 1.0 mg, (iv) 1.7 mg, or (v) 2.4 mg of semaglutide. In some embodiments, the pharmaceutical composition contains one to four unit dosage forms of semaglutide. In some embodiments, the pharmaceutical composition is contained in an injection device or vial.

[0077] In some embodiments, a pharmaceutical composition containing 7.2 mg of semaglutide may be replaced by three pharmaceutical compositions, each containing a unit dosage form of 2.4 mg of semaglutide. Thus, in some embodiments, a pharmaceutical composition intended to contain 7.2 mg of semaglutide may alternatively use three pharmaceutical compositions, each containing a unit dosage form of 2.4 mg of semaglutide. In this way, a fifth dose of 2.4 mg of semaglutide can also be used up to a sixth dose of 7.2 mg of semaglutide by administering the three unit dosage forms.

[0078] The pharmaceutical compositions described herein may further comprise one or more pharmaceutically acceptable excipients selected from the group consisting of, for example, buffer systems, preservatives, isotonic agents, chelating agents, stabilizers, and surfactants. In some embodiments, the pharmaceutical composition comprises one or more pharmaceutically acceptable excipients, such as one or more selected from the group consisting of buffer systems, isotonic agents, and preservatives. Formulations of pharmaceutically active ingredients with various excipients are known in the art; see, for example, Remington: The Science and Practice of Pharmacy (e.g., 19th edition (1995), and any subsequent editions). The term “excipient” broadly refers to any component other than the active therapeutic ingredient, e.g., semaglutide. Excipients may be inactive substances, inactive substances, and / or substances that are not pharmaceutically active (also referred to here as the active ingredient).

[0079] In some embodiments, semaglutide is administered in the form of a pharmaceutical composition comprising semaglutide and one or more excipients. In some embodiments, semaglutide is administered in the form of a pharmaceutical composition comprising semaglutide and one or more excipients, and the composition has a pH in the range of about 5.6 to about 10.0.

[0080] In some embodiments, the pharmaceutical composition has a pH in the range of about 6.5 to about 10, such as about 7.0 to about 9.5 or about 7.2 to about 9.0. In some embodiments, the pharmaceutical composition has a pH in the range of 7.0 to about 9.5, such as about 7.0 to about 9.5 or about 7.2 to about 9.5. In some embodiments, the pharmaceutical composition has a pH in the range of about 6.8 to 9.0, such as about 7.0 to about 8.5 or about 7.0 to about 8.0. In some embodiments, the pharmaceutical composition has a pH in the range of 7.0 to 8.5, such as about 6.8 to about 7.8 or about 7.0 to about 7.6. The pharmaceutical composition may have a pH in the range of about 6.0 to about 9.0. The pharmaceutical composition may have a pH in the range of about 6.8 to about 8.0. The pharmaceutical composition may have a pH in the range of about 7.0 to about 7.8. In some embodiments, the pharmaceutical composition has a pH in the range of about 5.6 to 7.6 or about 7.2 to about 7.6, such as 7.4. In some embodiments, the pharmaceutical composition has a pH of about 5.6 to about 7.6. In some embodiments, the pharmaceutical composition has a pH of about 7.2 to about 7.6. In some embodiments, the pharmaceutical composition has a pH of about 7.4. In some embodiments, the pharmaceutical composition has a pH of at least 5.6, at least 5.7, at least 5.8, at least 5.9, at least 6.0, at least 6.1, at least 6.2, at least 6.3, at least 6.4, at least 6.5, at least 6.6, at least 6.7, at least 6.8, at least 6.9, at least 7.0, at least 7.1, or at least 7.2. In some embodiments, the pharmaceutical composition has a pH of 9.5 or less. 9.4 or less, 9.3 or less, 9.2 or less, 9.1 or less, 9.0 or less, 8.9 or less, 8.8 or less, 8.7 or less, 8.6 or less, 8.5 or less, 8.4 or less, 8.3 or less, 8.2 or less, 8.1 or less, 8.0 or less, 7.9 or less, 7.8 or less, 7.7 or less, 7. Has a pH of 6 or less, 7.5 or less, 7.4 or less, 7.3 or less, 7.2 or less, 7.1 or less, 7.0 or less, 6.9 or less, 6.8 or less, 6.7 or less, 6.6 or less, 6.5 or less, 6.4 or less, 6.3 or less, 6.2 or less, 6.1 or less, or 6.0 or less.

[0081] In some embodiments, the pharmaceutical composition may include a buffer solution. In some embodiments, the pharmaceutical composition includes a phosphate buffer solution, such as sodium phosphate buffer, for example, disodium phosphate. In some embodiments, the pharmaceutical composition may include an isotonic agent. In some embodiments, the isotonic agent is propylene glycol or sodium chloride. The pharmaceutical composition may also include sodium chloride. In some embodiments, the pharmaceutical composition includes a preservative such as phenol.

[0082] In some embodiments, the pharmaceutical composition does not contain cyclodextrin. In some embodiments, the pharmaceutical composition does not contain preservatives.

[0083] The pharmaceutical composition may be in the form of a solution or a suspension. In some embodiments, the pharmaceutical composition is an aqueous composition, such as an aqueous solution or an aqueous suspension. The term "aqueous composition" may be defined as a composition containing water, such as at least 50% (w / w) water. Similarly, the term "aqueous solution" may be defined as a solution containing at least 50% (w / w) water, and the term "aqueous suspension" may be defined as a suspension containing at least 50% (w / w) water. In some embodiments, the aqueous composition contains at least 50% (w / w) water, such as at least 60% (w / w) or at least 70% (w / w) water. In some embodiments, the aqueous composition contains at least 80% (w / w) or at least 90% (w / w) water.

[0084] In some embodiments, semaglutide is administered in the form of a pharmaceutical composition comprising phosphate buffer and propylene glycol. In some embodiments, semaglutide is administered in the form of a pharmaceutical composition comprising about 2–15 mM phosphate buffer and about 2–25 mg / mL propylene glycol. In some embodiments, semaglutide is administered in the form of a pharmaceutical composition comprising about 0.1–20 mg / mL semaglutide, about 2–15 mM phosphate buffer, about 2–25 mg / mL propylene glycol, and a pH in the range of about 7.0–9.0. In some embodiments, semaglutide is administered in the form of a pharmaceutical composition comprising about 0.1–20 mg / mL semaglutide, about 2–15 mM phosphate buffer, about 2–25 mg / mL propylene glycol, about 1–18 mg / mL phenol, and a pH in the range of about 7.0–9.0. In some embodiments, semaglutide is administered in the form of a pharmaceutical composition containing about 1.0 mg / mL of semaglutide, about 1.42 mg / mL of disodium phosphate dihydrate, about 14.0 mg / mL of propylene glycol, about 5.5 mg / mL of phenol, and a pH of about 7.4. In some embodiments, semaglutide is administered in the form of a pharmaceutical composition containing about 0.5–4 mg / mL of semaglutide, about 1.42 mg / mL of disodium phosphate dihydrate, about 14.0 mg / mL of propylene glycol, about 5.5 mg / mL of phenol, and a pH of about 7.4. In some embodiments, semaglutide is administered in the form of a pharmaceutical composition containing about 0.5–1.5 mg / mL of semaglutide, about 1.42 mg / mL of disodium phosphate dihydrate, about 14.0 mg / mL of propylene glycol, about 5.5 mg / mL of phenol, and a pH of about 7.4. In some embodiments, semaglutide is administered in the form of a pharmaceutical composition comprising approximately 1.0–3.5 mg / mL of semaglutide, approximately 1.42 mg / mL of disodium phosphate dihydrate, approximately 14.0 mg / mL of propylene glycol, approximately 5.5 mg / mL of phenol, and a pH of approximately 7.4.

[0085] In some embodiments, semaglutide is administered in the form of a pharmaceutical composition comprising phosphate buffer and sodium chloride. In some embodiments, semaglutide is administered in the form of a pharmaceutical composition comprising about 2–15 mM phosphate buffer and about 2–25 mg / mL sodium chloride. In some embodiments, semaglutide is administered in the form of a pharmaceutical composition comprising about 0.1–20 mg / mL semaglutide, about 2–15 mM phosphate buffer, about 2–25 mg / mL sodium chloride, and a pH in the range of about 7.0–9.0. In some embodiments, semaglutide is administered in the form of a pharmaceutical composition comprising about 0.1–20 mg / mL semaglutide, about 2–15 mM phosphate buffer, about 2–25 mg / mL sodium chloride, about 1–18 mg / mL phenol, and a pH in the range of about 7.0–9.0. In some embodiments, semaglutide is administered in the form of a pharmaceutical composition containing about 1.0 mg / mL of semaglutide, about 1.42 mg / mL of disodium phosphate dihydrate, about 14.0 mg / mL of sodium chloride, about 5.5 mg / mL of phenol, and a pH of about 7.4. In some embodiments, semaglutide is administered in the form of a pharmaceutical composition containing about 0.5–4 mg / mL of semaglutide, about 1.42 mg / mL of disodium phosphate dihydrate, about 14.0 mg / mL of sodium chloride, about 5.5 mg / mL of phenol, and a pH of about 7.4. In some embodiments, semaglutide is administered in the form of a pharmaceutical composition containing about 0.5–1.5 mg / mL of semaglutide, about 1.42 mg / mL of disodium phosphate dihydrate, about 14.0 mg / mL of sodium chloride, about 5.5 mg / mL of phenol, and a pH of about 7.4. In some embodiments, semaglutide is administered in the form of a pharmaceutical composition containing approximately 1.0–3.5 mg / mL of semaglutide, approximately 1.42 mg / mL of disodium phosphate dihydrate, approximately 14.0 mg / mL of sodium chloride, approximately 5.5 mg / mL of phenol, and a pH of approximately 7.4.

[0086] In some embodiments, the pharmaceutical composition comprises semaglutide and caglirintide. Semaglutide and caglirintide may be administered in the form of the pharmaceutical composition described in WO2021 / 144476. Semaglutide and caglirintide may be administered in the form of the pharmaceutical composition described in WO2023 / 110833. Semaglutide and caglirintide may be administered in the form of the pharmaceutical composition described in WO2024 / 256632.

[0087] The pharmaceutical composition containing semaglutide and kaglirintide may preferably have a pH of about 5.6 to 6.2, for example, in the range of 5.6 to 6.0 or 5.8 to 6.2.

[0088] The concentration of caglilintide in the pharmaceutical compositions disclosed herein may be about 0.25 mg / ml to about 22 mg / ml. The concentration of amyrin receptor agonist may be at least about 0.25 mg / ml. The concentration of amyrin receptor agonist in the pharmaceutical formulation may be up to about 22 mg / ml. The concentration of amyrin receptor agonist may be such that it provides any one of the doses specified herein.

[0089] Manufacturing method GLP-1 receptor agonists and / or amyrin receptor agonists may be produced by classical peptide synthesis, such as solid-phase peptide synthesis using t-Boc or Fmoc chemistry, or by other well-established techniques, as described in Greene and Wuts, “Protective Groups in Organic Synthesis”, John Wiley & Sons, 1999; Florencio Zaragoza Dorwald, “Organic Synthesis on Solid Phase”, Wiley-VCH Verlag GmbH, 2000; and “Fmoc Solid Phase Peptide Synthesis”, Edited by WCChan and PDWhite, Oxford University Press, 2000.

[0090] Alternatively, GLP-1 receptor agonists may be produced by recombinant expression technology, for example, by culturing host cells containing a DNA sequence encoding a peptide sequence and capable of expressing the peptide in a suitable nutrient medium under conditions that allow for peptide expression. Non-limiting examples of host cells suitable for the expression of these peptides include Escherichia coli, Saccharomyces cerevisiae, and mammalian BHK or CHO cell lines.

[0091] GLP-1 receptor agonists containing one or more non-proteinogenic amino acids can also be semi-synthetically produced using a combination of recombinant expression techniques and chemical peptide synthesis as described in WO2009 / 083549. For compounds containing one or more non-natural amino acids and / or covalently bonded N-terminal monopeptides or dipeptide mimetic, see also Hodgson et al. in “The synthesis of peptides and proteins containing non-natural amino acids”, Chemical Society Reviews, vol.33, no.7(2004), pp. 422-430.

[0092] Once the GLP-1 receptor agonist and / or amyrin receptor agonist are manufactured and purified, the pharmaceutical compositions disclosed herein may be in a configuration prepared using the method described in WO2023 / 187067.

[0093] Alternatively, or subsequently, the composition containing the active pharmaceutical ingredient may be freeze-dried or spray-dried using methods known to those skilled in the art. Ohtake, S., Izutsu, K., & Lechuga-Ballesteros, D. (Eds.) describe such methods in “Drying technologies for biotechnology and pharmaceutical applications” (2020) John Wiley & Sons. The composition containing the active pharmaceutical ingredient and cyclodextrin to be dried may further contain a surfactant such as polysorbate 20 and / or 80.

[0094] If the composition is intermediately freeze-dried or spray-dried, the dried formulation may be dissolved in an aqueous solution or “reconstituted” before use. The reconstituted aqueous solution may be labeled on the vial. The reconstituted aqueous solution may contain, or consist of, a predetermined amount of water for injection. The reconstituted aqueous solution may contain, or consist of, a predetermined amount of water for injection and one or more preservatives. The reconstituted aqueous solution may contain, or consist of, a predetermined amount of water for injection and phenol and / or m-cresol and / or EDTA. The reconstituted aqueous solution may contain, or consist of, a predetermined amount of water for injection and m-cresol and / or EDTA. The reconstituted aqueous solution may contain, or consist of, a predetermined amount of water for injection and phenol and / or m-cresol. The reconstituted aqueous solution may contain, or consist of, a predetermined amount of water for injection and phenol. The reconstituted aqueous solution may contain, or consist of, a predetermined amount of water and m-cresol for injection. The reconstituted aqueous solution may contain, or consist of, a predetermined amount of water and EDTA for injection. The reconstituted aqueous solution may further contain a buffer having at least one pKa value of about 5.0 to 7.0, such as histidine or citrate. The reconstituted aqueous solution may further contain sorbitol.

[0095] Unless otherwise specified, the scope of this disclosure includes its endpoint. In some embodiments, the term "a" means "one or more." In some embodiments, unless otherwise indicated in this disclosure, terms presented in the singular also include plural situations. In this specification, the terms "about" and "approximately" may be understood to allow for standard variations as understood by those skilled in the art. In some embodiments, the term "about" means ±10% of the value mentioned and includes that value. In some embodiments, where used in this disclosure, the term "including" includes "consisting of." In some embodiments, the pH values ​​mentioned in this disclosure are measured at 25°C. Semaglutide 2.4 mg may be referred to in this disclosure as "semaglutide 2.4."

[0096] Non-limiting embodiments of the present invention The present invention can be further described by the following non-limiting embodiments.

[0097] 1. A method for weight management for subjects requiring weight management, comprising subcutaneous administration of semaglutide in an amount of approximately 7.2 mg per week. 2. A method for weight management in a human subject requiring the same, comprising subcutaneous administration of approximately 6.0 to approximately 7.2 mg of semaglutide per week. 3. A method for weight management for subjects requiring weight management, comprising subcutaneous administration of semaglutide in an amount of approximately 7.2 mg per week. 4. A method for weight management for subjects requiring weight management, comprising subcutaneous administration of approximately 7.2 mg of semaglutide once a week. 5. A method for the treatment of obesity or overweight, comprising subcutaneously administering approximately 7.2 mg of semaglutide once weekly to a subject in need thereof. 6. A method for the treatment of obesity, comprising subcutaneously administering approximately 7.2 mg of semaglutide once a week to a subject in need thereof. 7. A method for the treatment of overweight, comprising subcutaneously administering approximately 7.2 mg of semaglutide once a week to a subject in need thereof. 8. A method for treating overweight, comprising subcutaneously administering approximately 7.2 mg of semaglutide once weekly to a subject in need thereof, wherein the subject further has at least one weight-related comorbidity. 9. The method according to any one of the prior embodiments, wherein the subject is obese or overweight. 10. The method according to any one of the prior embodiments, wherein the subject is obese. 11. The method according to any one of the prior embodiments, wherein the subject is overweight. 12. The method according to any one of the prior embodiments, wherein the subject is overweight and has at least one weight-related comorbidity. 13. The method according to any one of the preceding embodiments, wherein the comorbidities related to body weight are selected from the group consisting of diabetes mellitus, cardiovascular disease, fatty liver disease associated with metabolic dysfunction, alcoholic liver disease, and obstructive sleep apnea. 14. The substance in question has a density of at least 30 kg / m³ 2 A method according to any one of the prior embodiments, having a BMI. 15. The substance in question has a density of at least 35 kg / m³ 2 A method according to any one of the prior embodiments, having a BMI. 16. The substance in question has a density of at least 40 kg / m³ 2 A method according to any one of the prior embodiments, having a BMI. 17. The substance in question has a density of at least 30-50 kg / m³ 2 A method according to any one of the prior embodiments, having a BMI. 18. The substance in question has a density of at least 30-45 kg / m³ 2 A method according to any one of the prior embodiments, having a BMI. 19. The substance in question has a density of at least 30-40 kg / m³ 2 A method according to any one of the prior embodiments, having a BMI. 20. The substance in question has a density of at least 30-35 kg / m³ 2 A method according to any one of the prior embodiments, having a BMI. 21. The substance in question has a density of at least 27 kg / m³ 2 A method according to any one of the prior embodiments, having a BMI. 22. The substance in question has a density of at least 27-30 kg / m³ 2 A method according to any one of the prior embodiments, having a BMI. 23. The substance in question has a density of at least 30 kg / m³ 2 The method according to any one of the prior embodiments, wherein the person has a BMI of and a body weight of at least about 100 kg. 24. The substance in question has a density of at least 30 kg / m³ 2 The method according to any one of the prior embodiments, wherein the person has a BMI of and a body weight of at least about 120 kg. 25. The substance in question has a density of at least 30 kg / m³ 2 The method according to any one of the prior embodiments, wherein the person has a BMI of and a body weight of at least about 140 kg. 26. The method according to any one of the prior embodiments, wherein the subject is an adult or a child. 27. The method according to any one of the prior embodiments, wherein the subject is an adult. 28. The method according to any one of the prior embodiments, wherein the subject is a child. 29. The method according to any one of the prior embodiments, wherein the subject is a child aged 12 years or older. 30. The subject is a child, and the amount is at least 30 kg / m² compared to that of an adult. 2 A method according to any one of the prior embodiments, having a BMI corresponding to the 31. The method according to any one of the prior embodiments, wherein the subject has diabetes. 32. The method according to any one of the preceding embodiments, wherein the subject has diabetes such as type 2 diabetes. 33. A method according to a prior embodiment, wherein the subject has at least one weight-related comorbidity, such as dyslipidemia or hypertension. 34. A method according to a prior embodiment, wherein the subject has overweight and at least one weight-related comorbidity, such as dyslipidemia or hypertension. 35. The subject has a minimum load of 27 kg / m³. 2 A method according to a prior embodiment, wherein the BMI and at least one weight-related comorbidity such as dyslipidemia or hypertension. 36. A method relating to any one of the prior embodiments in which the subject is not classified as New York Heart Association (NYHA) Class IV. 37. The method according to any one of the prior embodiments, wherein the semaglutide is administered at a dose of approximately 7.2 mg per week. 38. The method according to any one of the prior embodiments, wherein the semaglutide is administered once a week. 39. The method according to any one of the prior embodiments, wherein the semaglutide is administered once a week in an amount of approximately 7.2 mg. 40. The method according to any one of the prior embodiments, wherein the semaglutide is administered once a week in a dose of 7.2 mg. 41. The method according to any one of the prior embodiments, wherein the semaglutide is administered for at least 24 weeks. 42. The method according to any one of the prior embodiments, wherein the semaglutide is administered for at least 32 weeks. 43. The method according to any one of the prior embodiments, wherein the semaglutide is administered for at least 40 weeks. 44. The method according to any one of the prior embodiments, wherein the semaglutide is administered for at least 52 weeks. 45. The method according to any one of the prior embodiments, wherein the semaglutide is administered for at least 72 weeks. 46. ​​The method according to any one of the prior embodiments, wherein the semaglutide is administered for approximately 72 weeks. 47. The method according to any one of the preceding embodiments, wherein the semaglutide is administered for at least about 72 weeks from the initial semaglutide dose escalation step. 48. The method according to any one of the preceding embodiments, wherein the semaglutide is administered for up to approximately 72 weeks from the initial semaglutide dose escalation step. 49. The method according to any one of the prior embodiments, wherein the semaglutide is administered for at least about 72 weeks, including dose escalation. 50. The method according to any one of the preceding embodiments, wherein the semaglutide is administered for approximately 72 weeks, including dose escalation. 51. The method according to any one of the prior embodiments, wherein the semaglutide is administered at a dose of approximately 7.2 mg per week for at least approximately 52 weeks. 52. The method according to any one of the prior embodiments, wherein the subcutaneous administration further comprises one or more dose-escalation steps of semaglutide up to approximately 2.4 mg per week, followed by a dose of approximately 7.2 mg per week. 53. The method according to any one of the prior embodiments, wherein the subcutaneous administration further comprises one or more dose-escalation steps of approximately 0.25 mg to approximately 2.4 mg of semaglutide per week, followed by a dose of approximately 7.2 mg of semaglutide per week. 54. The method according to any one of the preceding embodiments, wherein the subcutaneous administration comprises a dose escalation step of approximately 2.4 mg of semaglutide per week, followed by a dose escalation step of approximately 7.2 mg of semaglutide per week. 55. The method according to any one of the preceding embodiments, further comprising one or more dose escalation steps of administering semaglutide up to approximately 2.4 mg per week prior to administering approximately 7.2 mg per week of semaglutide. 56. The method according to any one of the preceding embodiments, wherein the administration includes a dose escalation step of administering approximately 2.4 mg of semaglutide per week prior to administering approximately 7.2 mg of semaglutide per week. 57. The method according to any one of the preceding embodiments, wherein the subcutaneous administration includes a dose escalation step for up to approximately 20 weeks, for example, approximately 20 weeks. 58. The method according to any one of the preceding embodiments, wherein the subcutaneous administration includes a dose escalation step of approximately 2.4 mg or less of semaglutide per week, followed by approximately 7.2 mg of semaglutide per week for a maximum of approximately 20 weeks. 59. The method according to any one of the prior embodiments, wherein the subcutaneous administration comprises doses of approximately 0.25 mg of semaglutide per week, approximately 0.5 mg of semaglutide per week, approximately 1.0 mg of semaglutide per week, approximately 1.7 mg of semaglutide per week, approximately 2.4 mg of semaglutide per week, followed by approximately 7.2 mg of semaglutide per week, administered approximately every four weeks. 60. The method according to any one of the preceding embodiments, wherein the method includes a dose escalation step of approximately 2.4 mg of semaglutide per week, one week prior to a first dose of approximately 7.2 mg of semaglutide per week. 61. The method according to any one of the preceding embodiments, wherein the method includes a dose escalation step of 2.4 mg of semaglutide once weekly, one week before a first dose of 7.2 mg of semaglutide once weekly. 62. The method according to any one of the preceding embodiments, wherein the method includes a dose escalation step from weekly administration of semaglutide in amounts of approximately (i) 0.25 mg to (ii) 0.5 mg to (iii) 1.0 mg to (iv) 1.7 mg to (v) 2.4 mg, before administering approximately 7.2 mg of semaglutide per week. 63. The method according to any one of the preceding embodiments, wherein the method includes a dose escalation step from a weekly administration of semaglutide, in amounts of approximately (i) 0.25 mg to (ii) 0.5 mg to (iii) 1.0 mg to (iv) 1.7 mg to (v) 2.4 mg, before a weekly administration of approximately 7.2 mg of semaglutide. 64. The method according to any one of the preceding embodiments, wherein the method includes a dose escalation step of approximately (i) 0.25 mg to (ii) 0.5 mg to (iii) 1.0 mg to (iv) 1.7 mg to (v) 2.4 mg once weekly, starting from the once weekly administration of semaglutide, before the once weekly administration of approximately 7.2 mg of semaglutide. 65. The method according to any one of the preceding embodiments, wherein the method includes a dose escalation step every four weeks from the weekly administration of semaglutide, in amounts of (i) 0.25 mg to (ii) 0.5 mg to (iii) 1.0 mg to (iv) 1.7 mg to (v) 2.4 mg, before administering 7.2 mg of semaglutide once weekly. 66. A method according to any one of the prior embodiments, wherein the method provides weight loss to the subject. 67. The method according to any one of the prior embodiments, wherein the weight loss is at least about 15%, for example, at least about 18%, or at least about 20%. 68. The method according to any one of the prior embodiments, wherein the semaglutide provides a weight loss of at least about 15%, such as at least 18% or at least 20%. 69. The method according to any one of the prior embodiments, wherein the weight loss is at least about 15%. 70. The method according to any one of the prior embodiments, wherein the weight loss is at least about 18%. 71. The method according to any one of the prior embodiments, wherein the weight loss is at least about 20%. 72. The method according to any one of the prior embodiments, wherein the weight loss is at least about 25%.

[0098] 73. The method according to any one of the prior embodiments, wherein semaglutide provides a weight loss of at least about 15%, such as at least 18% or at least 20%. 74. The method according to any one of the prior embodiments, wherein approximately 7.2 mg of semaglutide per week provides a weight loss of at least about 15%, such as at least 18% or at least 20%. 75. The method according to any one of the prior embodiments, wherein approximately 7.2 mg of semaglutide per week administered for at least 52 weeks, including at least 72 weeks including dose escalation, provides at least approximately 15%, for example, at least 18% or at least 20% weight loss. 76. The method according to any one of the prior embodiments, wherein approximately 7.2 mg of semaglutide per week administered for at least 52 weeks provides a weight loss of at least about 15%, such as at least 18% or at least 20%. 77. The method according to any one of the prior embodiments, wherein approximately 7.2 mg per week of semaglutide administered for at least approximately 72 weeks, including dose escalation, provides at least approximately 15%, for example, at least 18% or at least 20% weight loss. 78. The method according to any one of the prior embodiments, wherein approximately 7.2 mg of semaglutide per week, administered for at least 52 weeks, results in a weight loss of at least approximately 15%. 79. The method according to any one of the prior embodiments, wherein approximately 7.2 mg of semaglutide per week, administered for at least 52 weeks, provides at least approximately 20% weight loss. 80. The method according to any one of the prior embodiments, wherein approximately 7.2 mg of semaglutide per week, administered for at least 52 weeks, provides at least approximately 25% weight loss. 81. The method according to any one of the preceding embodiments, wherein the weight loss is at least about 15% after administration of about 7.2 mg of semaglutide for at least about 52 weeks. 82. The method according to any one of the prior embodiments, wherein the weight loss is at least about 15% after administration of about 7.2 mg of semaglutide for about 52 weeks. 83. The method according to any one of the prior embodiments, wherein the weight loss is at least 15% after approximately 52 weeks of administration of 7.2 mg of semaglutide. 84. The method according to any one of the prior embodiments, wherein the weight loss is at least 18% after administration of 7.2 mg of semaglutide for approximately 52 weeks. 85. The method according to any one of the prior embodiments, wherein the weight loss is at least 20% after administration of approximately 7.2 mg of semaglutide for at least approximately 52 weeks. 86. The method according to any one of the prior embodiments, wherein the weight loss is at least 25% after administration of approximately 7.2 mg of semaglutide for at least approximately 52 weeks. 87. The method according to any one of the prior embodiments, wherein the weight loss is up to 75%. 88. The method according to any one of the prior embodiments, wherein the weight loss is up to 75% after administration of approximately 7.2 mg of semaglutide for at least approximately 52 weeks. 89. The method according to any one of the prior embodiments, wherein a larger proportion of subjects obtain at least a 20% weight loss with weekly administration of 7.2 mg of semaglutide compared to weekly administration of 2.4 mg of semaglutide. 90. The method according to any one of the prior embodiments, wherein at least 45% of the subjects, for example about 50%, obtain at least a 20% weight loss with 7.2 mg of semaglutide. 91. The method according to any one of the prior embodiments, wherein a larger proportion of subjects obtain at least a 25% weight loss with the administration of approximately 7.2 mg of semaglutide once weekly compared with 2.4 mg of semaglutide once weekly. 92. The method according to any one of the prior embodiments, wherein at least 25% of the subjects, e.g., at least 30%, e.g., at least about 33%, obtain at least 25% weight loss with about 7.2 mg of semaglutide. 93. A larger proportion of the target is 27 kg / m 2 A method according to any one of the prior embodiments for obtaining a BMI of less than a certain value. 94. A larger proportion of subjects responded to the aforementioned dose of approximately 7.2 mg of semaglutide per week compared to approximately 2.4 mg of semaglutide per week. 、 27 kg / m 2 A method according to any one of the prior embodiments for obtaining a BMI of less than a certain value. 95. A larger proportion of the subjects showed an improvement of 27 kg / m² with the 7.2 mg semaglutide once weekly dose compared to 2.4 mg semaglutide once weekly. 2A method according to any one of the prior embodiments for obtaining a BMI of less than a certain value. 96. At least about 25%, for example, about 27%, of the subjects responded to 7.2 mg of semaglutide with a dose of 27 kg / m². 2 A method according to any one of the prior embodiments for obtaining a BMI of less than a certain value. 97. A larger proportion of subjects showed improvement with the aforementioned dose of approximately 7.2 mg of semaglutide per week compared to approximately 2.4 mg of semaglutide per week. 、 27 kg / m 2 A method according to any one of the prior embodiments for obtaining a BMI of less than a certain value. 98. A larger proportion of the subjects showed an improvement of 27 kg / m² with the 7.2 mg semaglutide once weekly dose compared to 2.4 mg semaglutide once weekly. 2 A method according to any one of the prior embodiments for obtaining a BMI of less than a certain value. 99. The method according to any one of the prior embodiments, wherein the method provides a reduction of less than 20%, for example, less than 18% or less than 16% of the amount of fat excluding total fat. 100. A method according to any one of the prior embodiments, wherein the method provides a reduction of 15% or less of the amount of fat excluding the total amount of fat. 101. A method according to any one of the prior embodiments, wherein the method provides a reduction of approximately 10% to approximately 20% of the amount of fat excluding the total amount of fat. 102. A method according to any one of the prior embodiments, wherein the method is tolerable with respect to the subject. 103. The method according to any one of the prior embodiments, wherein the proportion of patients discontinuing administration of approximately 7.2 mg of semaglutide is less than approximately 15%. 104. The method according to any one of the prior embodiments, wherein the proportion of patients discontinuing administration of approximately 7.2 mg of semaglutide is approximately 8% to approximately 15%. 105. The method according to any one of the prior embodiments, wherein the proportion of patients discontinuing administration of approximately 7.2 mg of semaglutide is approximately 8% to approximately 15%. 106. The method according to any one of the prior embodiments, wherein the proportion of subjects discontinuing administration of approximately 7.2 mg of semaglutide within at least approximately 52 weeks is less than approximately 15%. 107. The method according to any one of the prior embodiments, wherein the proportion of subjects discontinuing administration of approximately 7.2 mg of semaglutide within at least approximately 52 weeks of the initial dose escalation is less than 15%, and the dose escalation is as defined herein. 108. The method according to any one of the preceding embodiments, wherein the proportion of patients who discontinue administration of approximately 7.2 mg of semaglutide within at least approximately 52 weeks after an initial dose escalation of up to approximately 2.4 mg of semaglutide once weekly is less than 15%. 109. The method according to any one of the preceding embodiments, wherein the proportion of patients who discontinue administration of approximately 7.2 mg of semaglutide within a maximum of approximately 72 weeks from an initial semaglutide dose escalation step, such as an initial semaglutide dose escalation step of 0.25 mg of semaglutide once weekly, is less than 15%. 110. The method according to any one of the preceding embodiments, wherein the proportion of subjects discontinuing administration of approximately 7.2 mg of semaglutide within up to approximately 72 weeks from the initial semaglutide dose escalation step, such as an initial semaglutide dose escalation step of 0.25 mg of semaglutide once weekly, is less than 15%, and the method includes a dose escalation of up to approximately 2.4 mg of semaglutide once weekly. 111. The method according to any one of the prior embodiments, wherein the proportion of patients discontinuing administration of approximately 7.2 mg of semaglutide is less than approximately 12%. 112. The method according to any one of the prior embodiments, wherein the proportion of subjects discontinuing administration of approximately 7.2 mg of semaglutide within at least approximately 52 weeks is less than 12%. 113. The method according to any one of the prior embodiments, wherein the proportion of subjects discontinuing administration of approximately 7.2 mg of semaglutide within at least approximately 52 weeks of the initial dose escalation is less than 12%, and the dose escalation is as defined herein. 114. The method according to any one of the prior embodiments, wherein, after an initial dose escalation of approximately 2.4 mg of semaglutide once weekly, the proportion of patients discontinuing administration of approximately 7.2 mg of semaglutide within at least approximately 52 weeks is less than 12%. 115. The method according to any one of the prior embodiments, wherein the proportion of patients who discontinue administration of approximately 7.2 mg of semaglutide within a maximum of approximately 72 weeks from an initial semaglutide dose escalation step, such as an initial semaglutide dose escalation step of 0.25 mg of semaglutide once weekly, is less than 12%. 116. The method according to any one of the preceding embodiments, wherein the proportion of subjects discontinuing administration of approximately 7.2 mg of semaglutide within up to approximately 72 weeks from the initial semaglutide dose escalation step, such as an initial semaglutide dose escalation step of 0.25 mg of semaglutide once weekly, is less than 12%, and the method includes a dose escalation of up to approximately 2.4 mg of semaglutide once weekly. 117. The method according to any one of the prior embodiments, wherein the suspension is a permanent suspension, such as a suspension for at least four weeks or at least eight weeks. 118. The method according to any one of the prior embodiments, wherein the proportion of subjects discontinuing administration of approximately 7.2 mg of semaglutide is less than approximately 15%, and the semaglutide provides at least approximately 15% weight loss. 119. The method according to any one of the prior embodiments, wherein the proportion of subjects discontinuing administration of approximately 7.2 mg of semaglutide is less than approximately 15%, and the semaglutide provides at least approximately 15% weight loss. 120. The method according to any one of the prior embodiments, wherein the proportion of subjects discontinuing administration of approximately 7.2 mg of semaglutide is less than approximately 15%, and the semaglutide provides at least approximately 15% weight loss. 121. The method according to any one of the prior embodiments, wherein approximately 65% ​​to approximately 75% of subjects experience at least one gastrointestinal adverse event. 122. The method according to any one of the prior embodiments, wherein approximately 65% ​​to 75% of subjects experience at least one gastrointestinal adverse event during administration of approximately 7.2 mg of semaglutide within approximately 52 weeks. 123. The method according to any one of the prior embodiments, wherein approximately 71% of subjects experience at least one gastrointestinal adverse event during administration of approximately 7.2 mg of semaglutide within approximately 52 weeks. 124. The method according to any one of the prior embodiments, wherein approximately 71% of the subjects experience at least one gastrointestinal adverse event during administration of approximately 7.2 mg of semaglutide within approximately 72 weeks, including dose escalation. 125. The method according to any one of the prior embodiments, wherein approximately 65% ​​to approximately 75% of subjects experience at least one gastrointestinal adverse event. 126. The method according to any one of the prior embodiments, wherein approximately 35% to approximately 50% of subjects experience at least one gastrointestinal adverse event. 127. The method according to any one of the prior embodiments, wherein approximately 40% to approximately 48% of subjects experience at least one gastrointestinal adverse event. 128. The method according to any one of the prior embodiments, wherein approximately 44% of the subjects have at least one gastrointestinal adverse event. 129. A method according to any one of the prior embodiments, wherein the waist circumference of the subject is reduced. 130. A method according to any one of the prior embodiments, wherein the blood pressure of the subject is reduced. 131. The method according to any one of the prior embodiments, wherein the diastolic and / or systolic blood pressure of the subject is reduced. 132. The method according to any one of the prior embodiments, wherein the diastolic and systolic blood pressure of the subject is reduced. 133. The method according to any one of the prior embodiments, wherein the semaglutide is administered by subcutaneous administration or subcutaneous injection. 134. The method according to any one of the prior embodiments, wherein the semaglutide is administered in the form of a pharmaceutical composition comprising semaglutide and one or more pharmaceutically acceptable excipients. 135. The method according to any one of the prior embodiments, wherein the semaglutide is administered in the form of a pharmaceutical composition comprising semaglutide and one or more pharmaceutically acceptable excipients. 136. The method according to any one of the prior embodiments, wherein the semaglutide is administered in the form of a pharmaceutical composition comprising semaglutide and one or more pharmaceutically acceptable excipients. 137. The method according to any one of the prior embodiments, wherein the pharmaceutical composition is a solution. 138. The method according to any one of the prior embodiments, wherein the pharmaceutical composition is an aqueous solution. 139. The method according to any one of the preceding embodiments, wherein the semaglutide is administered in the form of a pharmaceutical composition comprising semaglutide and one or more pharmaceutically acceptable excipients, the composition having a pH in the range of about 5.5 to about 10.0. 140. The method according to any one of the prior embodiments, wherein the pharmaceutical composition has a pH in the range of about 5.6 to about 10.0. 141. The method according to any one of the prior embodiments, wherein the pharmaceutical composition has a pH in the range of about 6.0 to about 9.0. 142. The method according to any one of the prior embodiments, wherein the pharmaceutical composition has a pH in the range of about 6.8 to about 8.0. 143. The method according to any one of the prior embodiments, wherein the pharmaceutical composition has a pH in the range of about 7.0 to about 7.8. 144. The method according to any one of the prior embodiments, wherein the pharmaceutical composition has a pH in the range of about 7.2 to about 7.6. 145. The method according to any one of the prior embodiments, wherein the pharmaceutical composition has a pH of about 7.4. 146. The method according to any one of the prior embodiments, wherein the pharmaceutical composition comprises a buffer. 147. The method according to any one of the prior embodiments, wherein the pharmaceutical composition comprises a phosphate buffer. 148. The method according to any one of the prior embodiments, wherein the pharmaceutical composition comprises an isotonic agent. 149. The method according to any one of the prior embodiments, wherein the pharmaceutical composition comprises sodium chloride. 150. The method according to any one of the prior embodiments, wherein the pharmaceutical composition does not contain cyclodextrin. 151. A liquid pharmaceutical composition according to any of the preceding embodiments, wherein the pharmaceutical composition does not contain a preservative. 152. A liquid pharmaceutical composition according to any of the preceding embodiments, wherein the pharmaceutical composition contains a preservative. 153. The method according to any one of the prior embodiments, wherein the semaglutide is contained in a vial. 154. The method according to any one of the prior embodiments, wherein the semaglutide is contained in an injection device. 155. The method according to any one of the prior embodiments, wherein the semaglutide is administered via an injection device. 156. A method for treating cardiovascular disease or reducing the risk of cardiovascular disease in a human subject in need thereof, comprising subcutaneous administration of approximately 7.2 mg of semaglutide per week. 157. A method according to a prior embodiment, wherein the present method is defined in any one of embodiments 9 to 155. 158. A method for reducing the risk of major adverse cardiovascular events, including cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke, in a human subject where such reduction is required, comprising subcutaneous administration of approximately 7.2 mg of semaglutide per week. 159. A method according to a prior embodiment, wherein the present method is defined in any one of embodiments 9 to 155. 160. A method for treating or reducing heart failure in a human subject requiring treatment or reduction of the risk of heart failure, comprising subcutaneous administration of approximately 7.2 mg of semaglutide per week. 161. A method according to a prior embodiment, wherein the present method is defined in any one of embodiments 9 to 155. 162. A method for treating metabolic dysfunction-associated steatohepatitis (MASH) in a human subject requiring treatment, comprising subcutaneous administration of approximately 7.2 mg of semaglutide per week. 163. A method according to a prior embodiment, wherein the present method is defined in any one of embodiments 9 to 155. 164. A method for treating alcoholic liver disease (ALD) in a human subject requiring treatment, comprising subcutaneous administration of approximately 7.2 mg of semaglutide per week. 165. A method according to a prior embodiment, wherein the present method is defined in any one of embodiments 9 to 155. 166. A method for treating type 2 diabetes in a human subject requiring treatment, comprising subcutaneous administration of approximately 7.2 mg of semaglutide per week. 167. A method according to a prior embodiment, wherein the present method is defined in any one of embodiments 9 to 155. 168. A method for the treatment of Alzheimer's disease in human subjects requiring the treatment thereof, comprising subcutaneous administration of approximately 7.2 mg of semaglutide per week. 169. A method according to a prior embodiment, wherein the present method is defined in any one of embodiments 9 to 155. 170. A method for treating chronic kidney disease in a human subject requiring treatment, comprising subcutaneous administration of approximately 7.2 mg of semaglutide per week. 171. A method according to a prior embodiment, wherein the present method is defined in any one of embodiments 9 to 155. 172. A method for the treatment of peripheral artery disease in human subjects requiring the use thereof, comprising subcutaneous administration of approximately 7.2 mg of semaglutide per week. 173. A method according to a prior embodiment, wherein the present method is defined in any one of embodiments 9 to 155. 174. A method for treating obstructive sleep apnea in human subjects requiring such treatment, such as those who are overweight or obese, comprising subcutaneous administration of approximately 7.2 mg of semaglutide per week. 175. The method according to any one of the prior embodiments, wherein the Alzheimer's disease is an early-stage Alzheimer's disease. 176. The method according to any one of the preceding embodiments, wherein the heart failure is heart failure with preserved ejection fraction. 177. A method according to any one of the prior embodiments, wherein the method includes administering another active ingredient. 178. The method according to any one of the prior embodiments, wherein the method further comprises the administration of caglilintide. 179. The method according to any one of the preceding embodiments, wherein the caglilintide is administered simultaneously with or sequentially to the semaglutide. 180. The method according to any one of the preceding embodiments, wherein the caglilintide is administered by subcutaneous injection. 181. The method according to any one of the preceding embodiments, wherein the caglilintide is administered by subcutaneous injection. 182. The method according to any one of the prior embodiments, wherein the caglilintide is administered at a dose of approximately 0.25 to 16 mg per week. 183. The method according to any one of the prior embodiments, wherein the caglilintide is administered in an amount of approximately 0.25 to 9.0 mg per week. 184. The method according to any one of the prior embodiments, wherein the caglilintide is administered in an amount of approximately 0.25 to 4.5 mg per week. 185. 186. The method according to any one of the prior embodiments, wherein the caglilintide is administered at a dose of approximately 0.25 mg per week. 187. The method according to any one of the prior embodiments, wherein the caglilintide is administered at a dose of approximately 0.5 mg per week. 188. The method according to any one of the prior embodiments, wherein the caglilintide is administered at a dose of approximately 1.0 mg per week. 189. The method according to any one of the prior embodiments, wherein the caglilintide is administered at a dose of approximately 1.7 mg per week. 190. The method according to any one of the prior embodiments, wherein the caglilintide is administered at a dose of approximately 2.4 mg per week. 191. The method according to any one of the prior embodiments, wherein the caglilintide is administered at a dose of approximately 3.6 mg per week. 192. The method according to any one of the prior embodiments, wherein the caglilintide is administered once a week. 193. The method according to any one of the prior embodiments, wherein the caglilintide is administered once a week in an amount of approximately 0.25 to 16 mg. 194. The method according to any one of the prior embodiments, wherein the caglilintide is administered once a week in an amount of approximately 0.25 mg. 195. The method according to any one of the prior embodiments, wherein the caglilintide is administered once a week in an amount of approximately 0.5 mg. 196. The method according to any one of the prior embodiments, wherein the caglilintide is administered once a week in an amount of approximately 1.0 mg. 197. The method according to any one of the prior embodiments, wherein the caglilintide is administered once a week in an amount of approximately 1.7 mg. 198. The method according to any one of the prior embodiments, wherein the caglilintide is administered once a week in an amount of approximately 2.4 mg. 199. The method according to any one of the prior embodiments, wherein the caglilintide is administered in the form of a pharmaceutical composition comprising caglilintide and one or more pharmaceutically acceptable excipients. 200. The method according to any one of the preceding embodiments, wherein the caglirintide is administered in the form of a pharmaceutical composition comprising caglirintide, semaglutide, and one or more pharmaceutically acceptable excipients. 201. The method according to any one of the prior embodiments, wherein the semaglutide is administered in the form of a pharmaceutical composition comprising caglirintide, semaglutide, and one or more pharmaceutically acceptable excipients. 202. The method according to any one of the prior embodiments, wherein the pharmaceutical composition is in the form of a solution. 203. The method according to any one of the prior embodiments, wherein the pharmaceutical composition is in the form of an aqueous solution. 204. The method according to any one of the preceding embodiments, wherein the pharmaceutical composition comprising caglirintide and semaglutide has a pH in the range of 5.6 to 6.0. 205. The method according to any one of the prior embodiments, wherein the pharmaceutical composition comprising caglirintide and semaglutide has a pH in the range of 5.8 to 6.2. 206. The method according to any one of the preceding embodiments, wherein the pharmaceutical composition containing caglilintide has a pH in the range of 3.5 to 4.5, such as 4.0. 207. The method according to any one of the prior embodiments, wherein the pharmaceutical composition comprising caglilintide comprises a buffer. 208. The method according to any one of the preceding embodiments, wherein the pharmaceutical composition comprising caglilintide comprises glutamic acid, glutamic acid, lactic acid, lactate, acetic acid, or an acetic acid-based buffer. 209. The method according to any one of the prior embodiments, wherein the pharmaceutical composition comprising caglirintide comprises glutamic acid or a glutamic acid-based buffer. 210. The method according to any one of the prior embodiments, wherein the pharmaceutical composition comprising caglilintide comprises a lactic acid or lactate-based buffer. 211. The method according to any one of the prior embodiments, wherein the pharmaceutical composition comprising caglilintide comprises acetic acid or an acetic acid-based buffer. 212. Semaglutide for use in weight management, including subcutaneous administration of up to approximately 7.2 mg of semaglutide per week to human subjects. 213. Semaglutide for use in weight management, including subcutaneous administration of approximately 7.2 mg of semaglutide per week to human subjects. 214. Semaglutide for use as described in the prior embodiments, wherein the subject is overweight or obese. 215. Semaglutide for use in the treatment of obesity, including subcutaneous administration of approximately 7.2 mg of semaglutide per week to human subjects. 216. Semaglutide for use in the treatment of obesity, including subcutaneous administration of approximately 7.2 mg of semaglutide per week to human subjects. 217. Semaglutide for use according to any one of embodiments 212 to 216, wherein the use is as defined in any one of the methods of the preceding embodiments. 218. Use of semaglutide in the manufacture of pharmaceuticals for weight management, including subcutaneous administration of up to approximately 7.2 mg of semaglutide per week to human subjects. 219. Use of semaglutide in the manufacture of pharmaceuticals for weight management, including subcutaneous administration of approximately 7.2 mg of semaglutide per week to human subjects. 220. The method according to a prior embodiment, wherein the subject is overweight or obese. 221. Use of semaglutide in the manufacture of pharmaceuticals for the treatment of obesity, including subcutaneous administration of approximately 7.2 mg of semaglutide per week to human subjects. 222. Use of semaglutide in the manufacture of pharmaceuticals for the treatment of obesity, including subcutaneous administration of approximately 7.2 mg of semaglutide per week to human subjects. 223. The use according to any of embodiments 218 to 222, wherein the use described above is as defined in any one of the methods of the embodiments described above. 224. A pharmaceutical composition containing semaglutide formulated for subcutaneous administration of up to approximately 7.2 semaglutide granules per week. 225. A pharmaceutical composition containing semaglutide formulated for subcutaneous administration of approximately 7.2 semaglutide units per week. 226. A pharmaceutical composition comprising semaglutide formulated for subcutaneous administration of approximately 7.2 semaglutide units per week to human subjects who are overweight or obese. 227. A pharmaceutical composition comprising semaglutide formulated for subcutaneous administration of approximately 7.2 semaglutide units per week to obese human subjects. 228. A pharmaceutical composition according to any one of embodiments 224 to 227, further comprising a configuration defined in any one of the methods of a prior embodiment. 229. A kit comprising semaglutide and instructions for use, wherein the semaglutide is for subcutaneous administration at a maximum dose of approximately 7.2 semaglutides per week. 230. A kit comprising semaglutide and instructions for use, wherein the semaglutide is for subcutaneous administration at a dose of approximately 7.2 semaglutides per week. 231. The kit according to embodiment 229 or 230, wherein the semaglutide is contained in a vial. 232. The kit according to Embodiment 229 or 230, wherein the semaglutide is contained within the injection device. 233. A kit according to any one of embodiments 229 to 232, further comprising features defined in any one of the methods of a prior embodiment. 234. A pharmaceutical composition comprising semaglutide, for use in a method for weight management in human subjects requiring semaglutide-based weight management, comprising subcutaneous administration of approximately 7.2 mg of semaglutide per week. 235. The pharmaceutical composition according to Embodiment 234, wherein the weight management is the treatment of obesity or overweight, and for the treatment of overweight, the subject may have at least one weight-related comorbidity. 236. The pharmaceutical composition according to Embodiment 234 or 235, wherein at least 25% of subjects obtain at least 25% weight loss with approximately 7.2 mg of semaglutide. 237. A pharmaceutical composition according to any one of embodiments 234 to 236, wherein the method results in a weight loss of at least about 15%. 238. A pharmaceutical composition according to any one of embodiments 234 to 237, wherein the method results in a weight loss of at least 18%. 239. The pharmaceutical composition according to any one of embodiments 234 to 238, wherein the method provides a reduction of less than 20% of the amount of fat excluding the total fat amount. 240. The pharmaceutical composition according to any one of embodiments 234 to 239, wherein the semaglutide is administered for at least about 52 weeks, for example, about 72 weeks, from the initial semaglutide dose escalation step. 241. The pharmaceutical composition according to any one of Embodiments 234 to 240, wherein the subcutaneous administration further comprises one or more dose escalation steps of administering semaglutide up to approximately 2.4 mg per week prior to the administration of approximately 7.2 mg per week of semaglutide. 242. The pharmaceutical composition according to any one of Embodiments 234 to 241, wherein the semaglutide is administered once a week. 243. A pharmaceutical composition according to any one of embodiments 234 to 242, wherein the method does not involve the administration of cyclodextrin. 244. The pharmaceutical composition according to any one of embodiments 234 to 243, wherein the pharmaceutical composition has a pH in the range of about 5.6 to about 9.0. 245. The pharmaceutical composition according to any one of Embodiments 234 to 244, wherein the pharmaceutical composition comprises semaglutide and one or more excipients and has a pH in the range of about 5.6 to about 9.0. 246. The pharmaceutical composition according to Embodiment 245, wherein the pharmaceutical composition has a pH of 7.4. 247. The pharmaceutical composition according to any one of Embodiments 234 to 246, wherein the method further comprises subcutaneous administration of approximately 0.25 to 16 mg of caglirintide per week, such as once a week. 248. The pharmaceutical composition according to any one of Embodiments 234 to 247, wherein the caglilintide is administered in an amount of approximately 0.25 to approximately 9.0 mg, approximately 0.25 to approximately 4.5 mg, or approximately 0.25 to approximately 2.4 mg per week, such as once a week. 249. The pharmaceutical composition according to Embodiment 248, wherein the caglilintide is administered in an amount of approximately 2.4 mg or approximately 3.6 mg per week, such as once a week. 250. (i) Reduce the risk of major adverse cardiovascular events, including cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke, and other cardiovascular (CV) diseases. (ii) Fatty liver disease associated with metabolic dysfunction, and (iii) A method for treating or reducing one or more risks selected from the group consisting of chronic kidney disease, in a human subject in need thereof, A pharmaceutical composition according to any one of Embodiments 234 to 249 for use in a method comprising subcutaneous administration of approximately 7.2 mg of semaglutide per week. 251. A pharmaceutical composition characterized by comprising semaglutide or a pharmaceutically acceptable salt thereof. 252. The pharmaceutical composition according to Embodiment 251, characterized in that the concentration of semaglutide is in the range of 0.1 mg / ml to 100 mg / ml. 253. The pharmaceutical composition according to Embodiment 251 or 252, further comprising one or more additional active ingredients. 254. A pharmaceutical composition according to any one of embodiments 251 to 253, characterized in that it is for subcutaneous administration. JPEG2026122884000001.jpg6170255. A pharmaceutical composition according to any one of embodiments 251 to 254, characterized in that it is a subcutaneous injection solution. 256. A pharmaceutical composition according to any one of embodiments 251 to 255, characterized by having a pH in the range of 5.6 to 10.0. 257. A pharmaceutical composition according to any one of embodiments 251 to 256, characterized in that it does not contain cyclodextrin. 258. A pharmaceutical composition characterized by comprising semaglutide or a pharmaceutically acceptable salt thereof, used in the form of an aqueous solution for subcutaneous injection. 259. A pharmaceutical composition according to any one of embodiments 251 to 258, characterized in that it is contained in a medical device such as a vial or injection device. 260. The pharmaceutical composition according to Embodiment 259, characterized in that the medical device contains 251 to 254 single doses of up to 7.2 mg of semaglutide or a pharmaceutically acceptable salt thereof. 261. The pharmaceutical composition according to Embodiment 260, characterized in that the single dose is administered weekly. 262. The pharmaceutical composition according to any one of embodiments 259 to 261, characterized in that the medical device can release a subsequent dose of 2.4 mg of semaglutide or a pharmaceutically acceptable salt thereof up to three times per day. 263. The pharmaceutical composition according to Embodiment 259, characterized in that the medical device can release a single dose of up to 7.2 mg of semaglutide or a pharmaceutically acceptable salt thereof. 264. The pharmaceutical composition according to any one of embodiments 259 to 263, characterized in that the medical device contains a total of up to 28.8 mg of semaglutide or a pharmaceutically acceptable salt thereof. 265. A pharmaceutical composition according to any one of embodiments 251 to 264, characterized in that it is for weight management in human subjects. 266. A pharmaceutical composition according to any one of embodiments 251 to 264, characterized in that it is for treating, preventing and / or reducing the risk of disease. 267. The aforementioned disease is (i) Obesity, (ii) being overweight; (iii) Cardiovascular disease (CV) disease, such as reducing the risk of major adverse cardiovascular events including CV death, non-fatal myocardial infarction, and non-fatal stroke. (iv) Fatty liver disease associated with metabolic dysfunction, (v) Chronic kidney disease, (vi) Type 2 diabetes, and (vii) The pharmaceutical composition according to Embodiment 266, characterized in that it is selected from the group consisting of Alzheimer's disease. 268. A kit comprising a pharmaceutical composition as defined in any one of embodiments 251 to 267 and instructions for use. 269. A kit comprising semaglutide or a pharmaceutically acceptable salt thereof, and instructions for use. 270. A kit comprising semaglutide or a pharmaceutically acceptable salt thereof, and instructions for administering semaglutide to subjects requiring it at a maximum dose of 7.2 mg once weekly. 271. It is a kit, (i) A medical device containing a pharmaceutical composition comprising one to four single doses of up to 7.2 mg of semaglutide or a pharmaceutically acceptable salt thereof, (ii) A kit comprising instructions for administering semaglutide to a subject in need, at a maximum dose of 7.2 mg, once weekly. 272. It is a kit, (i) A medical device containing a pharmaceutical composition comprising one to four single doses of 2.4 mg of semaglutide or a pharmaceutically acceptable salt thereof, (ii) A kit comprising instructions for administering three doses at once to a subject requiring it. 273. It is a kit, (i) at least one medical device containing a pharmaceutical composition comprising semaglutide, A kit characterized by including an instruction manual. 274. The medical device, (a) A single dose of up to 7.2 mg of semaglutide or a pharmaceutically acceptable salt thereof, in doses of 1 to 4, or (b) A kit comprising a total of up to 28.8 mg of semaglutide or a pharmaceutically acceptable salt thereof. 275. It is a kit, (i) A first medical device comprising a first medical device containing a single-dose preparation of up to 7.2 mg of semaglutide or a pharmaceutically acceptable salt thereof in 1 to 4 doses, (ii) A second medical device, wherein the medical device contains a single-dose preparation for 1 to 4 doses of up to 16 mg of an amyrin receptor agonist or a pharmaceutically acceptable salt thereof, A kit characterized by including an instruction manual. 276. Medical devices, (a) A single dose of up to 7.2 mg of semaglutide or a pharmaceutically acceptable salt thereof, in doses of 1 to 4, or (b) A medical device comprising a total of up to 28.8 mg of semaglutide or a pharmaceutically acceptable salt thereof. 277. A medical device characterized by containing semaglutide in a first chamber and an amyrin receptor agonist in a second chamber, The first chamber contains one to four single doses of semaglutide or a pharmaceutically acceptable salt up to 7.2 mg. A medical device characterized in that the second chamber contains a single dose of up to 16 mg of an amyrin receptor agonist or a pharmaceutically acceptable salt thereof, for 1 to 4 doses. 278. Use of semaglutide or a pharmaceutically acceptable salt thereof for the manufacture of drugs, pharmaceutical compositions, combinations, and / or medical devices for the treatment, prevention, and / or reduction of the risk of disease. 279. Use of semaglutide or a pharmaceutically acceptable salt thereof, characterized in that the concentration of semaglutide is in the range of 0.1 mg / ml to 100 mg / ml, for the manufacture of drugs, pharmaceutical compositions, combinations, and / or medical devices. 280. Use of semaglutide or a pharmaceutically acceptable salt thereof, characterized in that it is for the manufacture of a pharmaceutical composition in which the concentration of semaglutide is in the range of 0.1 mg / ml to 100 mg / ml, wherein the pharmaceutical composition contains a single dose of 1 to 4 doses of up to 7.2 mg of semaglutide or a pharmaceutically acceptable salt thereof, for the purpose of treating, preventing, and / or reducing the risk of disease. 281. Use of semaglutide or a pharmaceutically acceptable salt thereof for the manufacture of a pharmaceutical composition in which the concentration of semaglutide is in the range of 0.1 mg / ml to 100 mg / ml, for the treatment, prevention, and / or reduction of the risk of disease, The composition is contained in the medical device, A method wherein the medical device contains one to four single-dose preparations of up to 7.2 mg of semaglutide or a pharmaceutically acceptable salt thereof. 282. Use of semaglutide or a pharmaceutically acceptable salt thereof in combination with an amyrin receptor agonist or a pharmaceutically acceptable salt thereof for the manufacture of drugs, pharmaceutical compositions, combinations, and / or medical devices for treating, preventing, and / or reducing the risk of disease. 283. Use of semaglutide or a pharmaceutically acceptable salt thereof, and amyrin receptor agonists or a pharmaceutically acceptable salt thereof, characterized for the manufacture of agents, pharmaceutical compositions, combinations, and / or medical devices for treating, preventing, and / or reducing the risk of disease. 284. The aforementioned disease, (i) Obesity, (ii) being overweight; (iii) Cardiovascular disease (CV) disease, such as reducing the risk of major adverse cardiovascular events including CV death, non-fatal myocardial infarction, and non-fatal stroke. (iv) Fatty liver disease associated with metabolic dysfunction, (v) Chronic kidney disease, (vi) Type 2 diabetes, and (vii) The use according to any one of embodiments 278 to 283, characterized in that it is selected from the group consisting of Alzheimer's disease.

[0099] Non-limiting aspects of the present invention The present invention can be further described by the following non-limiting embodiments.

[0100] 1. Use of a unit dosage form of semaglutide in the manufacture of a pharmaceutical composition used for weight management for subjects requiring weight management, wherein the unit dosage form of semaglutide contains a maximum of approximately 7.2 mg of semaglutide. 2. Use of a unit dosage form of semaglutide in the manufacture of a pharmaceutical composition used for weight management for subjects requiring weight management, wherein the unit dosage form of semaglutide contains approximately 6.0 mg to approximately 7.2 mg of semaglutide. 3. Use of a unit dosage form of semaglutide in the manufacture of a pharmaceutical composition used for weight management for subjects requiring weight management, wherein the unit dosage form of semaglutide contains approximately 7.2 mg of semaglutide. 4. Use of a unit dosage form of semaglutide in the manufacture of a pharmaceutical composition for the treatment of obesity or overweight in a subject requiring it, wherein the unit dosage form of semaglutide contains about 7.2 mg of semaglutide. 5. Use of a unit dosage form of semaglutide in the manufacture of a pharmaceutical composition for the treatment of obesity or overweight in a subject requiring it, wherein the subject further has at least one weight-related comorbidity, and the unit dosage form of semaglutide comprises about 7.2 mg of semaglutide. 6. The use according to embodiment 5, wherein the comorbidities related to body weight are selected from the group consisting of diabetes mellitus, cardiovascular disease, fatty liver disease associated with metabolic dysfunction, alcoholic liver disease, and obstructive sleep apnea. 7. Use as described in any one of the preceding embodiments, wherein the unit dosage form is a once-weekly dose. 8. The use described in any one of the preceding embodiments, wherein the pharmaceutical composition comprises 1 to 4 unit dosage forms. 9. The use described in any one of the preceding embodiments, wherein the pharmaceutical composition comprises a dosage form of 1 or 4 units. 10. The use described in any one of the preceding embodiments, wherein the pharmaceutical composition comprises one unit dosage form. 11. The use described in any one of the preceding embodiments, wherein the pharmaceutical composition is a solution. 12. The use described in any one of the preceding embodiments, wherein the pharmaceutical composition is an aqueous solution. 13. The use according to any one of the preceding embodiments, wherein the pharmaceutical composition further comprises an amyrin receptor agonist, preferably the amyrin receptor agonist being caglilintide. 14. The use according to any one of the preceding embodiments, wherein the pharmaceutical composition is contained in a medical device, for example, an injection device or a vial, and preferably the injection device is a pen-type syringe. 15. The use according to any one of the preceding embodiments, wherein the unit dosage form comprises three subunit dosage forms, for example, each subunit dosage form of semaglutide contains 2.4 mg of semaglutide. 16. The use according to embodiment 15, wherein the semaglutide subunit dosage form is contained in a medical device, for example, an injection device or a vial, preferably the injection device being a pen-type syringe. 17. The use according to embodiment 14, wherein the medical device comprises semaglutide in a first chamber and an amyrin receptor agonist in a second chamber. 18. The use according to embodiment 17, wherein the second chamber contains a maximum of 16 mg of an amyrin receptor agonist or a pharmaceutically acceptable salt thereof, in a once-weekly dose of 1 to 4 times, preferably the amyrin receptor agonist being caglilintide. 19. The use described in any one of the preceding embodiments, wherein the subject has a BMI of at least 28 kg / m2. 20. The use described in any one of the preceding embodiments, wherein the subject has a BMI of at least 30 kg / m2. 21. The use described in any one of the preceding embodiments, wherein the subject has a BMI of at least 35 kg / m2. 22. The use described in any one of the preceding embodiments, wherein the subject has a BMI of at least 40 kg / m2. 23. Use as described in any one of the preceding embodiments, wherein the subject has a BMI of 28-50 kg / m2. 24. Use as described in any one of the preceding embodiments, wherein the subject has a BMI of 28-45 kg / m2. 25. Use as described in any one of the preceding embodiments, wherein the subject has a BMI of 28-40 kg / m2. 26. Use as described in any one of the preceding embodiments, wherein the subject has a BMI of 28-35 kg / m2. 27. The use described in any one of the preceding embodiments, wherein the subject has a BMI of at least 24 kg / m2. 28. Use as described in any one of the preceding embodiments, wherein the subject has a BMI of 24-28 kg / m2. 29. The use according to any one of the preceding embodiments, wherein the subject has a BMI of at least 28 kg / m2 and a body weight of at least approximately 100 kg. 30. The use according to any one of the preceding embodiments, wherein the subject has a BMI of at least 28 kg / m2 and a body weight of at least approximately 120 kg. 31. The use according to any one of the preceding embodiments, wherein the subject has a BMI of at least 28 kg / m2 and a body weight of at least approximately 140 kg. 32. The use described in any one of the preceding descriptions, wherein the subject is an adult or a child. 33. Use as described in any one of the preceding descriptions, wherein the subject is a child aged 12 years or older. 34. Use as described in any one of the preceding embodiments, wherein the subject has diabetes. 35. The use described in any one of the preceding embodiments, wherein the subject has diabetes such as type 2 diabetes. 36. The use according to any one of the preceding embodiments, wherein the subject has at least one weight-related comorbidity, such as dyslipidemia or hypertension. 37. The use according to any one of the preceding embodiments, wherein the subject has overweight and at least one weight-related comorbidity such as dyslipidemia or hypertension. 38. The use according to any one of the preceding embodiments, wherein the subject has a BMI of at least 24 kg / m2 and at least one weight-related comorbidity such as dyslipidemia or hypertension. 39. Use described in any one of the preceding embodiments, wherein the subject described above is not classified as New York Heart Association (NYHA) Class IV. 40. The use described in any one of the preceding embodiments, wherein the pharmaceutical composition is for subcutaneous administration. 41. The use of the pharmaceutical composition as described in any one of the preceding embodiments, wherein the pharmaceutical composition is administered once a week. 42. The use according to any one of the preceding embodiments, wherein the pharmaceutical composition is administered once a week. 43. The use of the pharmaceutical composition according to any one of the preceding embodiments, wherein the pharmaceutical composition is administered for at least 24 weeks. 44. The use according to any one of the preceding embodiments, wherein the pharmaceutical composition is administered for at least 32 weeks. 45. The use of the pharmaceutical composition according to any one of the preceding embodiments, wherein the pharmaceutical composition is administered for at least 40 weeks. 46. ​​The use according to any one of the preceding embodiments, wherein the pharmaceutical composition is administered for at least 52 weeks. 47. The use of the pharmaceutical composition according to any one of the preceding embodiments, wherein the pharmaceutical composition is administered for at least 72 weeks. 48. The use of the pharmaceutical composition as described in any one of the preceding embodiments, wherein the pharmaceutical composition is administered for approximately 72 weeks. 49. The use according to any one of the preceding embodiments, wherein the pharmaceutical composition is administered for at least about 72 weeks from the initial semaglutide dose escalation step. 50. The use according to any one of the preceding embodiments, wherein the pharmaceutical composition is administered for up to approximately 72 weeks from the initial semaglutide dose escalation step. 51. The use according to any one of the preceding embodiments, wherein the pharmaceutical composition is administered for at least about 72 weeks, including dose escalation. 52. The use of the pharmaceutical composition according to any one of the preceding embodiments, wherein the pharmaceutical composition is administered for approximately 72 weeks, including dose escalation. 53. The use according to any one of the preceding embodiments, wherein the weight management or treatment provides weight loss to the subject. 54. The use according to any one of the preceding embodiments, wherein the weight loss is at least about 15%, such as at least about 18% or at least 20%. 55. The use according to any one of the preceding embodiments, wherein the weight loss is at least about 15%. 56. The use according to any one of the preceding embodiments, wherein the weight loss is at least 18%. 57. The use according to any one of the preceding embodiments, wherein the weight loss is at least 20%. 58. The use according to any one of the preceding embodiments, wherein the weight loss is at least 25%. 59. The use according to any one of the preceding embodiments, wherein the weight management or treatment provides a reduction of less than 20%, for example, less than 18% or less than 16% of the amount of fat excluding fat relative to total fat mass. 60. The use according to any one of the preceding embodiments, wherein the weight management or treatment provides a reduction of 15% or less of the amount of fat excluding fat compared to total fat mass. 61. Use according to any one of the preceding embodiments, wherein the weight management or treatment described above provides a reduction of approximately 10% to approximately 20% of the amount of fat excluding fat relative to the total fat mass. 62. The use described in any one of the preceding embodiments, wherein the weight management or treatment is tolerable to the subject. 63. The use described in any one of the preceding embodiments, wherein less than approximately 15% of the subjects discontinue administration of the pharmaceutical composition. 64. The use described in any one of the preceding embodiments, wherein approximately 8% to approximately 15% of the subjects discontinue administration of the pharmaceutical composition. 65. The use described in any one of the preceding embodiments, wherein approximately 8% to approximately 15% of the subjects discontinue administration of the pharmaceutical composition. 66. The use described in any one of the preceding embodiments, wherein less than approximately 15% of the subjects discontinue administration of the pharmaceutical composition within at least approximately 52 weeks. 67. Use according to any one of the preceding embodiments, wherein less than 15% of the subjects discontinue administration of the pharmaceutical composition within at least about 52 weeks of the initial dose escalation, and such dose escalation is as defined herein. 68. The use described in any one of the preceding embodiments, wherein less than 12% of the subjects discontinue administration of the pharmaceutical composition. 69. The use according to any one of the preceding embodiments, wherein less than 12% of the subjects discontinue administration of the pharmaceutical composition within at least approximately 52 weeks. 70. The use according to any one of the preceding embodiments, wherein less than 12% of the subjects discontinue administration of the pharmaceutical composition within at least about 52 weeks of the initial dose escalation, and the dose escalation is as defined herein. 71. The use described in any one of the preceding embodiments, wherein the suspension is a permanent suspension, such as a suspension for at least four weeks or at least eight weeks. 72. Use according to any one of the preceding embodiments, wherein less than approximately 15% of the subjects discontinue administration of the pharmaceutical composition, and the weight management or treatment provides a weight loss of at least approximately 15%. 73. Use according to any one of the preceding embodiments, wherein less than approximately 15% of the subjects discontinue administration of the pharmaceutical composition, and the weight management or treatment provides a weight loss of at least approximately 15%. 74. Use according to any one of the preceding embodiments, wherein less than approximately 15% of the subjects discontinue administration of the pharmaceutical composition, and the weight management or treatment provides a weight loss of at least approximately 15%. 75. Use according to any one of the preceding embodiments, wherein approximately 65% ​​to approximately 75% of subjects experience at least one gastrointestinal adverse event. 76. The use according to any one of the preceding embodiments, wherein approximately 65% ​​to 75% of the subjects experience at least one gastrointestinal adverse event during administration of the pharmaceutical composition within approximately 52 weeks. 77. The use according to any one of the preceding embodiments, wherein approximately 71% of subjects experience at least one gastrointestinal adverse event during administration of the pharmaceutical composition within approximately 52 weeks. 78. The use according to any one of the preceding embodiments, wherein approximately 71% of subjects experience at least one gastrointestinal adverse event during administration of the pharmaceutical composition within approximately 72 weeks, including dose escalation. 79. Use according to any one of the preceding embodiments, wherein approximately 65% ​​to approximately 75% of subjects experience at least one gastrointestinal adverse event. 80. Use according to any one of the preceding embodiments, wherein approximately 35% to approximately 50% of subjects experience at least one gastrointestinal adverse event. 81. Use according to any one of the preceding embodiments, wherein approximately 40% to approximately 48% of subjects experience at least one gastrointestinal adverse event. 82. The use described in any one of the preceding embodiments, wherein approximately 44% of the subjects experience at least one gastrointestinal adverse event. 83. The use described in any one of the preceding embodiments, wherein the waist circumference of the subject is reduced. 84. The use described in any one of the preceding embodiments, wherein the blood pressure of the subject is reduced. 85. The use according to any one of the preceding embodiments, wherein the diastolic blood pressure and / or systolic blood pressure of the subject is reduced. 86. The use according to any one of the preceding embodiments, wherein the diastolic and systolic blood pressure of the subject is reduced. 87. The use according to any one of the preceding embodiments, wherein the semaglutide is administered subcutaneously by subcutaneous injection. 88. The use according to any one of the preceding embodiments, wherein the pharmaceutical composition comprises semaglutide and one or more excipients. 89. The use according to any one of the preceding embodiments, wherein the pharmaceutical composition essentially consists of semaglutide and one or more excipients. 90. The use described in any one of the preceding embodiments, wherein the pharmaceutical composition comprises semaglutide and one or more excipients. 91. The use according to any one of the preceding embodiments, wherein the pharmaceutical composition comprises semaglutide and one or more excipients, and the composition has a pH in the range of about 5.5 to about 10.0. 92. The use described in any one of the preceding embodiments, wherein the pharmaceutical composition has a pH in the range of about 5.6 to about 10.0. 93. The use described in any one of the preceding embodiments, wherein the pharmaceutical composition has a pH in the range of about 6.0 to about 9.0. 94. The use described in any one of the preceding embodiments, wherein the pharmaceutical composition has a pH in the range of about 6.8 to about 8.0. 95. The use described in any one of the preceding embodiments, wherein the pharmaceutical composition has a pH in the range of about 7.0 to about 7.8. 96. The use described in any one of the preceding embodiments, wherein the pharmaceutical composition has a pH in the range of about 7.2 to about 7.6. 97. The use of the pharmaceutical composition as described in any one of the preceding embodiments, wherein the pharmaceutical composition has a pH of approximately 7.4. 98. The use of the pharmaceutical composition according to any one of the preceding embodiments, wherein the pharmaceutical composition includes a buffer. 99. The use according to any one of the preceding embodiments, wherein the pharmaceutical composition further comprises a phosphate buffer and propylene glycol. 100. The use of the pharmaceutical composition as described in any one of the preceding embodiments, wherein the pharmaceutical composition contains an isotonic agent. 101. The use of the pharmaceutical composition as described in any one of the preceding embodiments, wherein the pharmaceutical composition contains sodium chloride. 102. The use of the pharmaceutical composition as described in any one of the preceding embodiments, wherein the pharmaceutical composition does not contain cyclodextrin. 103. The use of the pharmaceutical composition as described in any one of the preceding embodiments, wherein the pharmaceutical composition does not contain a preservative. 104. The use of the pharmaceutical composition as described in any one of the preceding embodiments, wherein the pharmaceutical composition contains a preservative. 105. The use according to any one of the preceding embodiments, wherein the pharmaceutical composition is administered via an injection device. 106. Use of approximately 7.2 mg of semaglutide in the manufacture of a pharmaceutical composition for treating or reducing the risk of cardiovascular disease in a subject requiring it. 107. The use described in the preceding embodiment, wherein the use is as defined in any one of embodiments 7 to 105. 108. Use of approximately 7.2 mg of semaglutide in the manufacture of pharmaceutical compositions to reduce the risk of major adverse cardiovascular events, including cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. 109. The use described in the preceding embodiment, wherein the use is as defined in any one of embodiments 7 to 105. 110. Use of approximately 7.2 mg of semaglutide in the manufacture of a pharmaceutical composition for treating or reducing heart failure in a subject requiring treatment of heart failure or reduction of the risk of heart failure. 111. The use described in the preceding embodiment, wherein the use is as defined in any one of embodiments 7 to 105. 112. Use of approximately 7.2 mg of semaglutide in the manufacture of a pharmaceutical composition for the treatment of metabolic dysfunction-associated steatohepatitis (MASH) in subjects requiring it. 113. The use described in the preceding embodiment, wherein the use is as defined in any one of embodiments 7 to 105. 114. Use of approximately 7.2 mg of semaglutide in the manufacture of a pharmaceutical composition for the treatment of alcoholic liver disease (ALD) in a patient requiring treatment for alcoholic liver disease (ALD). 115. The use described in the preceding embodiment, wherein the use is as defined in any one of embodiments 7 to 105. 116. Use of approximately 7.2 mg of semaglutide in the manufacture of a pharmaceutical composition for the treatment of type 2 diabetes in a subject requiring treatment for type 2 diabetes. 117. The use described in the preceding embodiment, wherein the use is as defined in any one of embodiments 7 to 105. 118. Use of approximately 7.2 mg of semaglutide in the manufacture of a pharmaceutical composition for the treatment of Alzheimer's disease in a subject requiring treatment for Alzheimer's disease. 119. The use described in the preceding embodiment, wherein the use is as defined in any one of embodiments 7 to 105. 120. Use of approximately 7.2 mg of semaglutide in the manufacture of a pharmaceutical composition for the treatment of chronic kidney disease in subjects requiring treatment for chronic kidney disease. 121. The use described in the preceding embodiment, wherein the use is as defined in any one of embodiments 7 to 105. 122. Use of approximately 7.2 mg of semaglutide in the manufacture of a pharmaceutical composition for the treatment of peripheral artery disease in subjects requiring it. 123. The use described in the preceding embodiment, wherein the use is as defined in any one of embodiments 7 to 105. 124. Use of approximately 7.2 mg of semaglutide in the manufacture of a pharmaceutical composition for the treatment of obstructive sleep apnea in subjects requiring it. 125. The use described in the preceding embodiment, wherein the use is as defined in any one of embodiments 7 to 105. 126. The use described in any one of the preceding embodiments, wherein the Alzheimer's disease is early Alzheimer's disease. 127. The use according to any one of the preceding embodiments, wherein the heart failure is heart failure with maintained ejection fraction. 128. The use described in any one of the preceding embodiments, wherein the treatment includes the administration of other active ingredients. 129. The use according to any one of the preceding embodiments, wherein the treatment further comprises the administration of caglilintide. 130. The use described in any one of the preceding embodiments, in which the caglilintide is administered simultaneously with or sequentially to the semaglutide. 131. The use described in any one of the preceding embodiments, wherein the caglilintide is administered by subcutaneous injection. 132. The use described in any one of the preceding embodiments, wherein the caglilintide is administered subcutaneously by subcutaneous injection. 133. The use described in any one of the preceding embodiments, wherein the amount of caglilintide is approximately 0.25 to 16 mg. 134. Use as described in any one of the preceding embodiments, wherein the amount of caglirintide is approximately 0.25 to 9.0 mg. 135. The use described in any one of the preceding embodiments, wherein the amount of caglilintide is approximately 0.25 to 4.5 mg. 136. The use described in any one of the preceding embodiments, wherein the amount of caglilintide is approximately 0.25 mg. 137. The use described in any one of the preceding embodiments, wherein the amount of caglilintide is approximately 0.5 mg. 138. The use described in any one of the preceding embodiments, wherein the amount of caglilintide is approximately 1.0 mg. 139 The use described in any one of the preceding embodiments, wherein the amount of caglilintide is approximately 1.7 mg. 140. The use described in any one of the preceding embodiments, wherein the amount of caglilintide is approximately 2.4 mg. 141. The use described in any one of the preceding embodiments, wherein the amount of caglilintide is approximately 3.6 mg. 142. The use of the caglilintide as described in any one of the preceding embodiments, wherein the caglilintide is administered once a week. 143. The use of the caglilintide as described in any one of the preceding embodiments, wherein the caglilintide is administered once a week. 144. The use described in any one of the preceding embodiments, wherein the pharmaceutical composition comprises caglirintide and one or more excipients. 145. The use described in any one of the preceding embodiments, wherein the pharmaceutical composition comprises caglirintide, semaglutide, and one or more excipients. 146. The use described in any one of the preceding embodiments, wherein the pharmaceutical composition comprises caglirintide, semaglutide, and one or more excipients. 147. The use according to any one of the preceding embodiments, wherein the pharmaceutical composition containing caglilintide is a solution. 148. The use described in any one of the preceding embodiments, wherein the pharmaceutical composition is in the form of an aqueous solution. 149. The use according to any one of the preceding embodiments, wherein the pharmaceutical composition comprising caglirintide and semaglutide has a pH in the range of 5.6 to 6.0. 150. The use according to any one of the preceding embodiments, wherein the pharmaceutical composition comprising caglirintide and semaglutide has a pH in the range of 5.8 to 6.2. 151. The use of the pharmaceutical composition containing caglilintide according to any one of the preceding embodiments, wherein the composition has a pH of approximately 3.5 to 4.5, for example, pH 4.0. 152. The use of the pharmaceutical composition according to any one of the preceding embodiments, wherein the pharmaceutical composition comprises a phosphate buffer. 153. The use of the pharmaceutical composition containing caglilintide according to any one of the preceding embodiments, wherein the pharmaceutical composition contains glutamic acid, glutamic acid, lactic acid, lactate, acetic acid, or an acetic acid-based buffer. 154. The use of the pharmaceutical composition containing caglirintide according to any one of the preceding embodiments, wherein the pharmaceutical composition contains glutamic acid or a glutamic acid-based buffer. 155. The use of the pharmaceutical composition containing caglilintide according to any one of the preceding embodiments, wherein the pharmaceutical composition contains lactic acid or a lactate-based buffer. 156. The use of the pharmaceutical composition containing caglilintide according to any one of the preceding embodiments, wherein the pharmaceutical composition contains acetic acid or an acetic acid-based buffer. 157. A combination of medications comprising: 1) a first dose containing approximately 0.25 mg of semaglutide, and / or 2) a second dose containing approximately 0.5 mg of semaglutide, 3) and / or a third dose containing approximately 1.0 mg of semaglutide, 4) and / or a fourth dose containing approximately 1.7 mg of semaglutide, 5) and / or a fifth dose containing approximately 2.4 mg of semaglutide, and 6) a sixth dose containing approximately 7.2 mg of semaglutide. 158. The combination of pharmaceuticals according to embodiment 157, wherein each dose is a once-weekly dose. 159. The pharmaceutical combination according to embodiment 157, wherein each dose is derived from a single-dose form or a multi-dose form. 160. The pharmaceutical combination according to embodiment 159, wherein the single-dose form includes a once-weekly dose. 161. The combination of pharmaceuticals described in embodiment 159, wherein the multiple-dose form includes a dose of 2 to 4 times a week, such as a dose of 4 times a week. 162. The pharmaceutical combination according to embodiment 157, wherein the sixth dose is administered in three unit dosage forms of 2.4 mg of semaglutide. 163. The drug combination described in embodiment 157, wherein dose escalation of each dose from 0.25 mg to 7.2 mg is carried out every four weeks. [Examples]

[0101] Example 1: Efficacy and safety of semaglutide 7.2 mg once weekly in obese patients A 72-week interventional, multinational, multicenter, randomized, parallel-group, double-blind, placebo-controlled clinical trial using semaglutide was conducted in 1407 obese adult human patients. From the start to the end of the clinical trial (weeks 0 to 72), patients received weekly subcutaneous administration of either semaglutide 7.2 mg, semaglutide 2.4 mg, or placebo (hereinafter simply referred to as semaglutide 7.2 mg, semaglutide 2.4 mg, and placebo) in addition to lifestyle interventions (reduced calorie diet and increased physical activity).

[0102] For patients treated with semaglutide, dose escalation was performed for semaglutide 2.4 mg and semaglutide 7.2 mg, starting with 0.25 mg (week 0), 0.5 mg (week 4), 1.0 mg (week 8), 1.7 mg (week 12), and 2.4 mg (week 16), followed by 2.4 mg (week 20) ​​or 7.2 mg (week 20) ​​every four weeks. Weeks 21–72 were a 52-week maintenance period with weekly subcutaneous administration of either semaglutide 7.2 mg, semaglutide 2.4 mg, or placebo. Weeks 73–82 were a 9-week follow-up period without administration of semaglutide 7.2 mg, semaglutide 2.4 mg, or placebo. Lifestyle interventions were also discontinued at week 72. Table 1 details the patient inclusion and exclusion criteria in the clinical trial. Screening occurred immediately before the first dose of semaglutide or placebo, such as approximately one week before the first dose. A subpopulation of randomized patients had body composition assessed by MRI (magnetic resonance imaging) at the start and end of the clinical trial, and the extent to which weight loss was caused by a reduction in fat mass was investigated. For the MRI subpopulation, MRI was performed from the spine T9 to the knee. Baseline characteristics of all randomized patients are listed in Table 2a, and the MRI subpopulations are listed in Table 2b. As used in this disclosure, the term “baseline” refers to the start of the clinical trial (week 0) and before the first dose of semaglutide or placebo.

[0103] Semaglutide was administered in the form of an aqueous solution at a pH of approximately 7.4. The aqueous solution containing semaglutide may further contain 1.42 mg / ml of disodium phosphate, dihydrate, and 8.25 mg / ml of sodium chloride. As used in this disclosure, the term placebo refers to a formulation identical to the semaglutide formulation, except that it does not contain semaglutide. Semaglutide 2.4 mg and placebo were also administered during dose escalation in a volume equivalent to that used for the 7.2 mg dose of semaglutide.

[0104] The primary endpoints were (i) the change in body weight (%) from baseline (week 0) to the end of treatment (week 72), and (ii) the proportion of patients with a body weight loss of ≥5% at the end of treatment (week 72). Secondary endpoints included the proportion of patients with a body weight loss of ≥15%, ≥20%, or ≥25% at the end of treatment.

[0105]

Table 1-1

Table 1-2

[0106] The baseline characteristics of the patients are shown in Tables 2a and 2b, respectively, for all randomized patients and the MRI subpopulation.

[0107]

Table 2-1

Table 2-2

[0108]

Table 3

[0109] Results may be presented for all randomized subjects as either in-treatment or hypothetical estimates. As used in this disclosure, the term in-treatment refers to all data points in which a patient is treated with the investigational drug (semaglutide or placebo), i.e., excluding any out-of-treatment time intervals triggered by at least two consecutive dose misses. As used in this disclosure, the term hypothetical estimate refers to a statistical analysis of data based on the assumption that all patients remained on the investigational product (semaglutide or placebo) for the entire planned duration of the clinical trial and did not initiate any other anti-obesity therapy (weight management medication or bariatric surgery). This estimate employed a mixed model for repeated measures (MMRM) using treatment data until the first discontinuation of the investigational product or initiation of other anti-obesity therapy. Randomized treatment was fitted as a factor, and all nested within visits as covariates to baseline values; missing values ​​at week 72 were predicted from the aforementioned MMRM.

[0110] The results are shown in Tables 3-10.

[0111] [Table 4-1] [Table 4-2]

[0112] The results in Table 3 show that semaglutide 7.2 mg resulted in significantly greater weight loss compared to semaglutide 2.4 mg or placebo, semaglutide 7.2 mg resulted in significantly greater blood pressure reduction for both HbA1c and fasting plasma glucose (FPG) compared to placebo, and semaglutide 7.2 mg resulted in significantly greater blood pressure reduction for both systolic and diastolic blood pressure compared to placebo.

[0113] [Table 5]

[0114] The results in Table 4 show that for semaglutide 7.2 mg, more patients achieved a weight loss of ≥5%, ≥10%, ≥15%, ≥20%, or ≥25% compared to semaglutide 2.4 mg or placebo. Furthermore, significantly more patients achieved a weight loss of ≥15%, ≥20%, or ≥25% compared to semaglutide 2.4 mg or placebo.

[0115]

Table 6-1

Table 6-2

[0116] The results in Table 5 show that for semaglutide 7.2 mg, more subjects had a shift to a lower BMI category at week 72 compared to semaglutide 2.4 mg or placebo when compared to baseline.

[0117]

Table 7

[0118] The results in Table 6 show a significantly higher proportion of patients who achieved a BMI of less than 7 kg / m2 for semaglutide 7.2 mg compared to semaglutide 2.4 mg or placebo. 2

[0119]

Table 8

[0120] The results in Table 7 show, surprisingly, that semaglutide 7.2 mg resulted in a greater reduction in both systolic and diastolic blood pressure compared to semaglutide 2.4 mg or placebo.

[0121]

Table 9

[0122] The results in Table 7a show, surprisingly, that only 16.4% (2.3 / 14.0) of the amount of fat excluding total fat was lost in the MRI subpopulation by using 7.2 mg of semaglutide (7.2 mg semaglutide), while 18.1% (2.3 / 12.7) of the amount of fat excluding total fat was lost in the MRI subpopulation by using pooled semaglutide (pooled semaglutide).

[0123] [Table 10]

[0124] [Table 11]

[0125] The results in Table 7c show, surprisingly, that semaglutide 7.2 mg achieved a waist-to-height ratio (WHtR) of less than 0.50, in addition to a greater reduction in waist circumference (WC), compared to semaglutide 2.4 mg or placebo. At week 72, a larger proportion of patients treated with semaglutide 7.2 mg (14.6%) achieved a WHtR < 0.50 compared to 2.4 mg (6.5%) and placebo (1.1%). At week 72, patients in the semaglutide 7.2 mg, semaglutide 2.4 mg, and placebo groups had mean reductions in WC of -18.9 cm, -15.9 cm, and -4.9 cm, respectively. The estimated treatment ratio (ETR) [95% CI] for semaglutide 7.2 mg versus semaglutide 2.4 mg was 2.5 [95% CI 1.5, 4.1], with p=0.0014 for waist height ratio <0.50. The estimated treatment difference (ETD) [95% CI] for semaglutide 7.2 mg versus semaglutide 2.4 mg was -3.0 [95% CI -4.6, -1.4, p=0.0003].

[0126] [Table 12]

[0127] The results in Table 8 are surprising, as the rate of patient discontinuation from the clinical trial for semaglutide 7.2 mg was similar to that for semaglutide 2.4 mg (11.6% and 11.9%, respectively), and the rate of patient discontinuation was higher for placebo than for semaglutide 7.2 mg or semaglutide 2.4 mg, indicating that semaglutide 7.2 mg was better tolerated than expected. This is particularly surprising considering the direct dose escalation of semaglutide from 2.4 mg to 7.2 mg.

[0128] Table 9. Gastrointestinal adverse events (GI-AEs), nausea, diarrhea, vomiting, or constipation were reported at weeks 0–72 for all randomized patients during treatment. Results are expressed as N(%), where N is the number of patients experiencing at least one event, and % is the proportion of patients in each group experiencing at least one event.

[0129] [Table 13]

[0130] Table 9 shows the rates of gastrointestinal adverse events, including nausea, diarrhea, vomiting, and constipation, for semaglutide 7.2 mg, semaglutide 2.4 mg, and placebo. Surprisingly, the tolerability of semaglutide 7.2 mg was better than expected, as the rate of patients experiencing diarrhea was similar to that of semaglutide 2.4 mg (27.1% and 27.9%, respectively).

[0131] Table 10a: Percentage of patients experiencing at least one adverse event at any point in time during treatment: (i) gastrointestinal adverse events (GI-AEs) between weeks 0 and 72 within exposure-level-based subgroups characterized by median semaglutide plasma concentration levels (nmol / liter), (ii) nausea, or (iii) vomiting. Outcomes for GI-AEs, nausea, or vomiting are expressed as mean (%). Semaglutide plasma concentration is expressed as median (nmol / liter). [Table 14]

[0132] Table 10b: Semaglutide plasma concentrations in patients undergoing treatment. Semaglutide plasma concentrations are expressed as median (nmol / liter). [Table 15]

[0133] The results in Table 10a show an increase in gastrointestinal adverse events, nausea, and vomiting associated with increased semaglutide plasma concentrations.

[0134] The results in Tables 10a–10b are based on steady-state semaglutide plasma concentrations for each subject, determined from a population pharmacokinetic (PK) model, and are based on randomized treatment dose levels. For patients administered semaglutide, the results in Table 10a were obtained based on these steady-state semaglutide plasma concentrations for each subject by classifying patients administered semaglutide from the lowest to the highest semaglutide plasma concentrations. This type of patient list was divided into five equally sized subgroups of approximately 250 patients, and the median semaglutide plasma concentration was then determined for each subgroup; and (b) the mean percentage of patients experiencing at least one adverse event for each GI-AE, nausea or vomiting, was determined for each subgroup. For patients who received placebo, the results in Table 10a were obtained based on the mean percentage of patients experiencing at least one adverse event for each of (a) semaglutide plasma concentration 0 and (b) GI-AE. Nausea or vomiting was observed in the placebo group.

[0135] The results in Table 10b show that the median plasma semaglutide concentration was 238 nmol / liter for semaglutide 7.2 mg and 76.4 nmol / liter for semaglutide 2.4 mg.

[0136] [Table 16]

[0137] The results for fasting serum insulin in Table 10c (columns 1-2) show that semaglutide 7.2 mg resulted in a significantly greater reduction in fasting serum insulin compared to placebo.

[0138] The lipid results in Table 11 (columns 3-13) show that semaglutide 7.2 mg resulted in a significantly greater reduction in total cholesterol, LDL cholesterol, VLDL cholesterol, triglycerides, and hsCRP compared to placebo, and a significantly greater increase in HDL cholesterol.

[0139] [Table 17-1] [Table 17-2]

[0140] The results in Table 10d show that with semaglutide 7.2 mg, more subjects experienced a change in blood glucose status from prediabetes to normal compared to semaglutide 2.4 mg or placebo.

[0141] Example 2: Efficacy and safety of semaglutide 7.2 mg once weekly in participants with obesity and type 2 diabetes. A 72-week interventional, multinational, multicenter, randomized, parallel-group, double-blind, placebo-controlled clinical trial using semaglutide was conducted in 512 adult humans with obesity and type 2 diabetes. From the start to the end of the clinical trial (weeks 0 to 72), patients received weekly subcutaneous administration of either semaglutide 7.2 mg, semaglutide 2.4 mg, or placebo (hereinafter simply referred to as semaglutide 7.2 mg, semaglutide 2.4 mg, and placebo) as an adjunct to lifestyle interventions (reduced calorie diet and increased physical activity).

[0142] For patients treated with semaglutide, dose escalation was performed for semaglutide 2.4 mg and semaglutide 7.2 mg, starting with 0.25 mg (week 0), 0.5 mg (week 4), 1.0 mg (week 8), 1.7 mg (week 12), and 2.4 mg (week 16), followed by 2.4 mg (week 20) ​​or 7.2 mg (week 20) ​​every four weeks. Weeks 21–72 were a 52-week maintenance period with weekly subcutaneous administration of either semaglutide 7.2 mg, semaglutide 2.4 mg, or placebo. Weeks 73–82 were a 9-week follow-up period without administration of semaglutide 7.2 mg, semaglutide 2.4 mg, or placebo. Lifestyle interventions were also discontinued at week 72. Table 11 details the patient selection and exclusion criteria in the clinical trial. Screening occurred immediately before the first dose of semaglutide or placebo, such as approximately one week before the first dose. Table 12 lists the baseline characteristics of all randomized patients. As used in this disclosure, the term “baseline” refers to the start of the clinical trial (week 0) and before the first dose of semaglutide or placebo.

[0143] Semaglutide was administered in aqueous solution at a pH of approximately 7.4. The aqueous solution containing semaglutide may further contain 1.42 mg / ml of disodium phosphate dihydrate and 8.25 mg / ml of sodium chloride. As used in this disclosure, the term placebo refers to a preparation identical to the semaglutide preparation, except that it does not contain semaglutide. Semaglutide 2.4 mg and placebo were administered during dose escalation at volumes used for an equivalent semaglutide 7.2 mg dose.

[0144] The primary endpoints were (i) the percentage change in body weight from baseline (week 0) to the end of treatment (week 72), and (ii) the proportion of patients with a weight loss of ≥5% at the end of treatment (week 72). Secondary endpoints included the proportion of patients with a weight loss of ≥20% at the end of treatment.

[0145] [Table 18-1] [Table 18-2]

[0146] Table 12 shows the baseline characteristics of all randomized patients.

[0147] [Table 19]

[0148] Results may be presented for all randomized subjects as either in-treatment or hypothetical estimates. As used in this disclosure, the term in-treatment refers to all data points in which a patient is treated with the investigational drug (semaglutide or placebo), i.e., excluding any out-of-treatment time intervals induced by at least two consecutive dose misses. As used in this disclosure, the term hypothetical estimate refers to a statistical analysis of data based on the assumption that all patients continued the investigational product (semaglutide or placebo) throughout the planned duration of the clinical trial and did not initiate any other anti-obesity therapy (weight management medication or bariatric surgery). This estimate employed a mixed model for repeated measures (MMRM) using in-treatment data until the first discontinuation of the investigational product, initiation of other anti-obesity therapy, or initiation of anti-diabetic rescue medication (applicable only to those intended to address glucose metabolism). Randomized treatment as a factor, and all nested within visits as a factor, were fitted to baseline values ​​as covariates; missing values ​​at week 72 were predicted from the aforementioned MMRM.

[0149] The results are shown in Tables 13-17.

[0150] [Table 20]

[0151] The results in Table 13 show that semaglutide 7.2 mg resulted in greater weight loss compared to semaglutide 2.4 mg or placebo. The results in Table 13 also show that semaglutide 7.2 mg resulted in greater reductions in waist circumference, HbA1c, body weight, BMI, fasting plasma glucose, and systolic blood pressure compared to semaglutide 2.4 mg and placebo.

[0152] [Table 21]

[0153] The results in Table 14 show that, compared to semaglutide 2.4 mg or placebo, more patients achieved a weight loss of ≥5%, ≥10%, ≥15%, or ≥20% with semaglutide 7.2 mg.

[0154] [Table 22]

[0155] The results in Table 15 are surprising, as the rate of patient discontinuation from the clinical trial for semaglutide 7.2 mg was similar to that for semaglutide 2.4 mg (9.4% and 8.7%, respectively), and the rate of patient discontinuation was higher for placebo than for semaglutide 7.2 mg or semaglutide 2.4 mg, indicating that semaglutide 7.2 mg was better tolerated than expected. This is particularly surprising considering the direct dose escalation of semaglutide from 2.4 mg to 7.2 mg.

[0156] Table 16. Gastrointestinal adverse events (GI-AEs), nausea, diarrhea, vomiting, or constipation were reported at weeks 0–72 for all randomized patients during treatment. Results are expressed as N(%), where N is the number of patients experiencing at least one event, and % is the proportion of patients in each group experiencing at least one event. [Table 23]

[0157] The results in Table 16 show gastrointestinal adverse events, including nausea, diarrhea, vomiting, and constipation, for semaglutide 7.2 mg, semaglutide 2.4 mg, and placebo. Surprisingly, the results were similar for semaglutide 7.2 mg and semaglutide 2.4 mg, and notably, a smaller percentage (%) of patients experienced diarrhea and constipation with semaglutide 7.2 mg compared to semaglutide 2.4 mg, while the percentage experienced diarrhea and constipation with semaglutide 7.2 mg compared to semaglutide 2.4 mg.

[0158] [Table 24-1] [Table 24-2]

[0159] Example 3: Combined administration of semaglutide and caglilintide in pigs Studies were conducted in LYD pigs to evaluate the pharmacokinetic (PK) profiles of caglilintide and semaglutide combination administration using pre-filled dual-chamber syringes or via separate injections of each drug. The administered volumes were approximately 500 microliters of semaglutide and approximately 250 microliters of caglilintide. The dose ranges of 0.25 mg to 2.4 mg of semaglutide and 0.25 to 4.5 mg of caglilintide were explored.

[0160] Female crossbred domestic pigs (Danish Landrace, Yorkshire, and Duroc-LYD pigs) weighing approximately 80-100 kg were used to explore PK profiles.

[0161] Low doses of semaglutide / caglilintide were administered subcutaneously as a single dose, either as monotherapy or in combination with pre-filled dual-chamber syringes or NovoPen 4 penfills (Novo Nordisk A / S) used as separate injections at different injection sites. Prior to administering high doses of semaglutide / caglilintide, LYD pigs were dose-escalated with liraglutide for 10 days to avoid initial gastrointestinal discomfort from rapid high-dose semaglutide. On day 11, the animals were administered semaglutide / caglilintide as described above.

[0162] For each animal, we obtained total plasma concentration-time profiles from before administration to 18 days after administration.

[0163] Plasma analysis of semaglutide and caglirintide was performed using luminescent oxygen channel immunoassay (LOCI) and liquid chromatography-mass spectrometry (LCMS), respectively. Non-compartmental pharmacokinetic analysis was performed using individual plasma concentration-time profiles.

[0164] [Table 25-1] [Table 25-2]

[0165] Moderate differences in semaglutide PK parameters, Cmax, and tmax were observed with different administration methods. For caglilintide, C max In contrast to administration of semaglutide via two different devices, the AUC increased by up to 65% after administration of 2.4 / 2.4 semaglutide / caglirintide using a pre-filled dual-chamber syringe, and the AUC increased by up to 45%.

[0166] These nonclinical data show that semaglutide and caglilintide exhibit improved efficacy when administered as a single injection using a dual-chamber syringe, compared to when they are administered separately using individual syringes such as NovoPen 4 Penfill.

[0167] Example 4: Combined administration of semaglutide and caglilintide in a Phase I human trial. Test design A 20-week repeated-dose escalation phase 1 trial investigated the safety, tolerability, pharmacokinetics, and potential weight loss of AM833 (caglirintide) administered in combination with 2.4 mg of semaglutide. The trial administered six different doses of caglirintide (0.16 mg, 0.3 mg, 0.6 mg, 1.2 mg, 2.4 mg, and 4.5 mg per week) together with semaglutide (2.4 mg per week) as separate subcutaneous injections to six distinct cohorts. Participants were randomized in a 3:1 ratio to receive either caglirintide + 2.4 mg of semaglutide or placebo + 2.4 mg of semaglutide. A 16-week dose escalation period was applied, followed by 4 weeks at the target dose. Weight range: 27.0–39.9 kg / m² 2 Eighty adults with an initial BMI (including both borderline values) completed the study.

[0168] This study investigated the number of adverse events (primary endpoint) that occurred during treatment. AM833 was well-tolerated, and the most common adverse events were injection site reactions and gastrointestinal disturbances, including nausea and vomiting, the majority of which were non-serious, mild, or moderate in severity. Surprisingly, the level of gastrointestinal disturbances observed with the AM833 and semaglutide combination in the study was comparable to that commonly seen with glucagon-like peptide-1 (GLP-1) monotherapy.

[0169] result From a mean baseline weight of 95.7 kg, weight decreased in all treatment groups over a 20-week treatment period, and substantial weight loss was observed in subjects receiving the three highest doses of caglirintide (1.2 mg, 2.4 mg, and 4.5 mg) + 2.4 mg semaglutide compared to placebo + 2.4 mg semaglutide (Figure 1).

[0170] After 20 weeks of treatment, there was a statistically significant difference in mean weight change from baseline to end of treatment for the three highest doses of caglilintide combined with semaglutide (1.2 mg, 2.4 mg, and 4.5 mg) compared to placebo + semaglutide. The estimated mean weight change from baseline to end of treatment was 15.6% for caglilintide 1.2 mg, 17.0% for caglilintide 2.4 mg, and 15.6% for caglilintide 4.5 mg, all combined with 2.4 mg of semaglutide. A weight loss of 9.8% was observed for placebo + semaglutide. For the three lowest doses of caglilintide combined with semaglutide (0.16 mg, 0.3 mg, and 0.6 mg), there was no statistically significant difference in treatment compared to placebo combined with 2.4 mg of semaglutide. In all treatment groups, there was evidence of weight regain after discontinuing the use of the investigational drug at week 20.

[0171] While certain features of the present invention are illustrated and described herein, many modifications, substitutions, alterations, and equivalents will be conceivable to those skilled in the art. It should therefore be understood that the appended claims are intended to encompass all such modifications and alterations that fall within the true spirit of the invention.

Claims

1. A pharmaceutical product used for weight management in human subjects requiring weight management, comprising semaglutide, wherein the semaglutide is administered subcutaneously to the subject at a dose of approximately 7.2 mg per week.

2. The pharmaceutical product according to claim 1, wherein the weight management is the treatment of obesity or overweight, and the subject may have at least one weight-related comorbidity with respect to the treatment of overweight.

3. The pharmaceutical product according to claim 1 or 2, wherein at least 25% of the subjects obtain at least 25% weight loss with approximately 7.2 mg of semaglutide.

4. The pharmaceutical product according to any one of claims 1 to 3, wherein the administration of semaglutide results in a weight loss of at least about 15%.

5. The pharmaceutical product according to any one of claims 1 to 4, wherein the administration of semaglutide results in a weight loss of at least 18%.

6. The pharmaceutical product according to any one of claims 1 to 5, wherein the administration of semaglutide results in a reduction of less than 20%, for example, less than 18%, of the amount of fat excluding total fat.

7. The pharmaceutical product according to any one of claims 1 to 6, wherein the subcutaneous administration further comprises one or more initial semaglutide dose escalation steps, in which semaglutide is administered to a maximum of approximately 2.4 mg per week before administration of approximately 7.2 mg per week of semaglutide.

8. The pharmaceutical product according to claim 7, wherein the semaglutide is administered for at least about 52 weeks, for example, about 72 weeks, from the initial semaglutide dose escalation step.

9. The pharmaceutical product according to any one of claims 1 to 8, wherein the semaglutide is administered once a week.

10. The pharmaceutical product according to any one of claims 1 to 9, wherein the semaglutide is not administered simultaneously with cyclodextrin.

11. The pharmaceutical product according to any one of claims 1 to 10, wherein the semaglutide is administered in the form of a pharmaceutical composition comprising the semaglutide, and the pharmaceutical composition has a pH in the range of about 5.6 to about 9.

0.

12. The pharmaceutical product according to any one of claims 1 to 11, wherein the semaglutide is administered in the form of a pharmaceutical composition comprising semaglutide and one or more excipients, the composition having a pH in the range of about 5.6 to about 9.

0.

13. The pharmaceutical composition according to any one of claims 11 or 12, wherein the pharmaceutical composition has a pH of about 7.

4.

14. The pharmaceutical product according to any one of claims 1 to 13, wherein the administration of semaglutide further comprises subcutaneous administration of approximately 0.25 to 16 mg of caglirintide per week, such as once a week.

15. The pharmaceutical product according to claim 14, wherein the caglilintide is administered in an amount of approximately 0.25 to approximately 9.0 mg, approximately 0.25 to approximately 4.5 mg, or approximately 0.25 to approximately 2.4 mg per week, such as once a week.

16. The pharmaceutical product according to claim 14 or 15, wherein the caglilintide is administered in an amount of approximately 2.4 mg or approximately 3.6 mg per week, such as once a week.

17. A pharmaceutical product containing semaglutide, which is used in human subjects requiring it, (i) Reduce the risk of major adverse cardiovascular events, including cardiovascular disease, such as cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. (ii) Fatty liver disease associated with metabolic dysfunction, and (iii) A pharmaceutical product for use in the treatment of or reduction of the risk of one or more diseases and / or disorders selected from the group consisting of chronic kidney disease, wherein such use comprises subcutaneous administration of approximately 7.2 mg of semaglutide per week.

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