Research Study to Investigate How Well Semaglutide Works Compared to Liraglutide in People Living With Overweight or Obesity

Study Overview
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Brief Summary
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This study will look at participants' body weight from the start to the end of the study. The study will last for about 1½ years. This is to compare the effect on body weight in people taking semaglutide once a week or people taking liraglutide once every day. Participants will either get semaglutide, liraglutide or dummy medicine. Which treatment is decided by chance. Participants who receive semaglutide or semaglutide dummy medicine will need to take 1 injection once a week. Participants who receive liraglutide or liraglutide dummy medicine will need to take 1 injection once daily. The study medicine is injected with a thin needle in a skin fold in the stomach, thigh or upper arm. During the study participants will have talks with study staff about eating healthy food and how to be more physically active. Participants will have 16 clinic visits and 7 phone calls with the study doctor. At 4 of the clinic visits participants cannot eat and drink (water is allowed) for 8 hours before the visit. Women cannot take part if pregnant, breast-feeding or planning to become pregnant during the study period.

Official Title
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Effect and Safety of Subcutaneous Semaglutide 2.4 mg Once Weekly Compared to Liraglutide 3.0 mg Once Daily on Weight Management in Subjects With Overweight or Obesity

Conditions
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Overweight, Obesity

Intervention / Treatment
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* Drug: Semaglutide
* Drug: Placebo (semaglutide)
* Drug: Liraglutide
* Drug: Placebo (liraglutide)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, age 18 years or older at the time of signing informed consent Body mass index (BMI) equal to or above 30.0 kg/m^2 or equal to or above 27.0 kg/m^2 with the presence of at least one of the following weight-related comorbidities (treated or untreated): hypertension, dyslipidaemia, obstructive sleep apnoea or cardiovascular disease History of at least one self-reported unsuccessful dietary effort to lose body weight Exclusion Criteria: HbA1c equal to or above 48 mmol/mol (6.5%) as measured by the central laboratory at screening History of type 1 or type 2 diabetes mellitus A self-reported change in body weight of more than 5 kg (11 lbs) within 90 days before screening irrespective of medical records

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Semaglutide<br>Semaglutide administered s.c. (subcutaneously, under the skin) adjunct to a reduced-calorie diet and increased physical activity | Drug: Semaglutide<br>* Dose gradually increased to 2.4 mg administered once weekly for 68 weeks<br>|
| Placebo Comparator: Placebo (semaglutide)<br>Placebo (semaglutide) administered s.c. adjunct to a reduced-calorie diet and increased physical activity | Drug: Placebo (semaglutide)<br>* Administered once weekly for 68 weeks<br>|
| Active Comparator: Liraglutide<br>Liraglutide administered s.c. adjunct to a reduced-calorie diet and increased physical activity | Drug: Liraglutide<br>* Dose gradually increased to 3.0 mg administered once daily for 68 weeks<br>|
| Placebo Comparator: Placebo (liraglutide)<br>Placebo (liraglutide) administered s.c. adjunct to a reduced-calorie diet and increased physical activity | Drug: Placebo (liraglutide)<br>* Administered once daily for 68 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline (Week 0) to Week 68 in Body Weight (%) (Semaglutide 2.4 mg Versus Liraglutide 3.0 mg) | Change from baseline (week 0) to week 68 in body weight (%) is presented. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site. | Baseline (week 0), week 68 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Who From Baseline (Week 0) to Week 68 Achieved Body Weight Reduction Greater Than or Equal to (>=) 10% (Yes/no) | Number of participants who achieved >= 10% weight reduction from baseline (week 0) to week 68 is presented. In the reported data, 'Yes' infers the number of participants who have achieved >= 10% weight reduction, whereas 'No' infers the number of participants who did not achieve >= 10% weight reduction. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site. | From baseline (week 0) to week 68 | 
| Number of Participants Who From Baseline (Week 0) to Week 68 Achieved Body Weight Reduction >=15% (Yes/no) | Number of participants who achieved >= 15% weight reduction from baseline (week 0) to week 68 is presented. In the reported data, 'Yes' infers the number of participants who have achieved >= 15% weight reduction, whereas 'No' infers the number of participants who did not achieve >= 15% weight reduction. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site. | From baseline (week 0) to week 68 | 
| Number of Participants Who From Baseline (Week 0) to Week 68 Achieved Body Weight Reduction >=20% (Yes/no) | Number of participants who achieved >= 20% weight reduction from baseline (week 0) to week 68 is presented. In the reported data, 'Yes' infers the number of participants who have achieved >= 20% weight reduction, whereas 'No' infers the number of participants who did not achieve >= 20% weight reduction. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site. | From baseline (week 0) to week 68 | 
| Change From Baseline (Week 0) to Week 68 in Waist Circumference | Change from baseline (week 0) to week 68 in waist circumference is presented. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site. | Baseline (week 0), week 68 | 
| Change From Baseline (Week 0) to Week 68 in Body Weight (Kilograms (kg)) | Change from baseline (week 0) to week 68 in body weight is presented. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site. | Baseline (week 0), week 68 | 
| Change From Baseline (Week 0) to Week 68 in Body Weight (%) (Semaglutide 2.4 mg Versus Pooled Placebo and Liraglutide 3.0 mg Versus Pooled Placebo) | Change from baseline (week 0) to week 68 in body weight (%) is presented. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site. | Baseline (week 0), week 68 | 
| Change From Baseline (Week 0) to Week 68 in Systolic Blood Pressure | Change from baseline (week 0) to week 68 in systolic blood pressure is presented. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site. | Baseline (week 0), week 68 | 
| Change From Baseline (Week 0) to Week 68 in Diastolic Blood Pressure | Change from baseline (week 0) to week 68 in diastolic blood pressure is presented. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site. | Baseline (week 0), week 68 | 
| Change From Baseline (Week 0) to Week 68 in Lipids: Total Cholesterol (Milligram Per Deciliter (mg/dL)) (Ratio to Baseline) | Change from baseline (week 0) to week 68 in total cholesterol (measured in mg/dL) is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site. | Baseline (week 0), week 68 | 
| Change From Baseline (Week 0) to Week 68 in Lipids: Total Cholesterol (Millimoles Per Liter (mmol/L)) (Ratio to Baseline) | Change from baseline (week 0) to week 68 in total cholesterol (measured in mmol/L) is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site. | Baseline (week 0), week 68 | 
| Change From Baseline (Week 0) to Week 68 in Lipids: High Density Lipoprotein (HDL) Cholesterol (mg/dL) (Ratio to Baseline) | Change from baseline (week 0) to week 68 in HDL cholesterol (measured in mg/dL) is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site. | Baseline (week 0), week 68 | 
| Change From Baseline (Week 0) to Week 68 in Lipids: High Density Lipoprotein (HDL) Cholesterol (mmol/L) (Ratio to Baseline) | Change from baseline (week 0) to week 68 in HDL cholesterol (measured in mmol/L) is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site. | Baseline (week 0), week 68 | 
| Change From Baseline (Week 0) to Week 68 in Lipids: Low Density Lipoprotein (LDL) Cholesterol (mg/dL) (Ratio to Baseline) | Change from baseline (week 0) to week 68 in LDL cholesterol (measured in mg/dL) is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site. | Baseline (week 0), week 68 | 
| Change From Baseline (Week 0) to Week 68 in Lipids: Low Density Lipoprotein (LDL) Cholesterol (mmol/L) (Ratio to Baseline) | Change from baseline (week 0) to week 68 in LDL cholesterol (measured in mmol/L) is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site. | Baseline (week 0), week 68 | 
| Change From Baseline (Week 0) to Week 68 in Lipids: Very Low Density Lipoprotein (VLDL) Cholesterol (mg/dL) (Ratio to Baseline) | Change from baseline (week 0) to week 68 in VLDL cholesterol (measured in mg/dL) is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site. | Baseline (week 0), week 68 | 
| Change From Baseline (Week 0) to Week 68 in Lipids: Very Low Density Lipoprotein (VLDL) Cholesterol (mmol/L) (Ratio to Baseline) | Change from baseline (week 0) to week 68 in VLDL cholesterol (measured in mmol/L) is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site. | Baseline (week 0), week 68 | 
| Change From Baseline (Week 0) to Week 68 in Lipids: Free Fatty Acids (FFA) (mg/dL) (Ratio to Baseline) | Change from baseline (week 0) to week 68 in FFA (measured in mg/dL) is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site. | Baseline (week 0), week 68 | 
| Change From Baseline (Week 0) to Week 68 in Lipids: Free Fatty Acids (FFA) (mmol/L) (Ratio to Baseline) | Change from baseline (week 0) to week 68 in FFA (measured in mmol/L) is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site. | Baseline (week 0), week 68 | 
| Change From Baseline (Week 0) to Week 68 in Lipids: Triglycerides (mg/dL) (Ratio to Baseline) | Change from baseline (week 0) to week 68 in triglycerides (measured in mg/dL) is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site. | Baseline (week 0), week 68 | 
| Change From Baseline (Week 0) to Week 68 in Lipids: Triglycerides (mmol/L) (Ratio to Baseline) | Change from baseline (week 0) to week 68 in triglycerides (measured in mmol/L) is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site. | Baseline (week 0), week 68 | 
| Change From Baseline (Week 0) to Week 68 in High-sensitivity C-reactive Protein (Hs-CRP): Ratio to Baseline | Change from baseline (week 0) to week 68 in hs-CRP (measured in mg/L) is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site. | Baseline (week 0), week 68 | 
| Change From Baseline (Week 0) to Week 68 in Glycated Haemoglobin (HbA1c) (%) | Change from baseline (week 0) to week 68 in HbA1c (%) is presented. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site. | Baseline (week 0), week 68 | 
| Change From Baseline (Week 0) to Week 68 in Glycated Haemoglobin (HbA1c) (Millimoles Per Mole (mmol/Mol)) | Change from baseline (week 0) to week 68 in HbA1c is presented. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site. | Baseline (week 0), week 68 | 
| Change From Baseline (Week 0) to Week 68 in Fasting Plasma Glucose (mg/dL) | Change from baseline (week 0) to week 68 in fasting plasma glucose is presented. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site. | Baseline (week 0), week 68 | 
| Change From Baseline (Week 0) to Week 68 in Fasting Plasma Glucose (mmol/L) | Change from baseline (week 0) to week 68 in fasting plasma glucose is presented. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site. | Baseline (week 0), week 68 | 
| Change From Baseline (Week 0) to Week 68 in Fasting Serum Insulin (Milli-international Units Per Liter (mIU/L)): Ratio to Baseline | Change from baseline (week 0) to week 68 in fasting serum insulin (measured in mIU/L) is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site. | Baseline (week 0), week 68 | 
| Change From Baseline (Week 0) to Week 68 in Fasting Serum Insulin (Picomoles Per Liter (Pmol/L)): Ratio to Baseline | Change from baseline (week 0) to week 68 in fasting serum insulin (measured in pmol/L) is presented as ratio to baseline. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site. | Baseline (week 0), week 68 | 
| Number of Participants at Baseline (Week 0) and Week 68 in Glycaemic Category (Normo-glycaemia, Pre-diabetes, Type 2 Diabetes (T2D)) | Number of participants in glycaemic categories, normo-glycaemia, pre-diabetes and type 2 diabetes at baseline (week 0) and 68 are presented. These categories were set as per the following criteria: 1) Normo-glycaemia: fasting plasma glucose (FPG) less than (<) 5.6 mmol/L (<100 mg/dL) and/or glycated haemoglobin (HbA1c) <5.7%; 2) Pre-diabetes: FPG 5.6 - 6.9 mmol/L (both inclusive), FPG 100 - 125 mg/dL (both inclusive) or HbA1c 5.7 - 6.4% (both inclusive); 3) Type 2 diabetes: FPG greater than or equal to (>=) 7.0 mmol/L (>=126 mg/dL) and/or HbA1c >=6.5%. Data is reported for 'in-trial' period: the uninterrupted time interval from date of randomization to date of last contact with trial site. | Baseline (week 0), week 68 | 
| Number of Participants Who From Baseline (Week 0) to Week 68 Permanently Discontinued Randomized Trial Product | Number of participants who from baseline (week 0) to week 68 permanently discontinued randomized trial product are presented. | From baseline (week 0) to week 68 | 
| Number of Treatment Emergent Adverse Events (TEAEs) From Baseline (Week 0) to Week 75 | An adverse event (AE) was any untoward medical occurrence in a clinical trial participant that was temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. All AEs mentioned here are TEAEs defined as AEs, with the onset of the event occurred in the on-treatment period. A time-point was considered on treatment if any dose of trial product has been administrated within the prior 49 days. | From baseline (week 0) to week 75 | 
| Number of Serious Adverse Events (SAEs) From Baseline (Week 0) to Week 75 | An AE was any untoward medical occurrence in a clinical trial participant that was temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE was defined as an AE that results in death, or is life-threatening, or requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, or is a congenital anomaly/birth defect. SAEs occurred based on the on-treatment period is presented. A time-point was considered on treatment if any dose of trial product has been administrated within the prior 49 days. | From baseline (week 0) to week 75 |