A Research Study to See How Semaglutide Helps People With Excess Weight and Type 2 Diabetes Lose Weight

Study Overview
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Brief Summary
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This study will look at how much weight participants will lose and how much blood sugar control they achieve from the start to the end of the study. The weight loss in participants taking the investigational high dose of semaglutide will be compared to the weight loss in people taking dummy medicine and a lower dose of semaglutide. In addition to taking the medicine, participants will have talks with study staff about healthy food choices and how to be more physically active. Participants will either get semaglutide or dummy medicine. Which treatment participants get is decided by chance. Participants are more likely (4 out of 5) to get semaglutide than the dummy medicine. The study medicine will be injected briefly, under skin, with a thin needle, typically in the stomach, thighs, or upper arms. After receiving first dose, the dose of semaglutide will be gradually increased until reaching the target dose. The study will last for about 1.5 years.

Official Title
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Effect and Safety of Semaglutide 7.2 mg Once-weekly in Participants With Obesity and Type 2 Diabetes

Conditions
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Obesity, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Semaglutide
* Drug: Semaglutide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female. Age above or equal to 18 years at the time of signing informed consent. BMI greater than or equal to 30.0 kilograms per square meter (kg/m^2). Diagnosed with type 2 diabetes (T2D) greater than or equal to 180 days prior to the day of screening. History of at least one self-reported unsuccessful dietary effort to lose body weight. HbA1c 7.0-10.0 percent (53-86 millimoles per mole [mmol/mol]) (both inclusive) as measured by central laboratory at screening. Exclusion Criteria: A self-reported change in body weight greater than 5 kilograms (kg) (11 pounds [lbs]) within 90 days before screening irrespective of medical records. Personal or first-degree relative(s) history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma. Renal impairment with estimated Glomerular Filtration Rate (eGFR) less than 30 milliliters per minute per 1.73 square meter (30 mL/min/1.73 m^2) (less than 45 mL/min/1.73 m^2 in participants treated with Sodium-glucose Cotransporter-2 [SGLT2i]) according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation as defined by Kidney Disease: Improving Global Outcomes (KDIGO) 2012 by the central laboratory at screening. Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within 90 days before screening or in the period between screening and randomization. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.

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 7.2 mg<br>Participants will receive once-weekly injection of semaglutide subcutaneously (s.c.) in 20 week dose escalation period with dose escalation (0.25 milligram [mg], 0.5 mg, 1.0 mg, 1.7 mg, 2.4 mg, and 7.2 mg) every fourth week. Treatment will be continued on the maintenance dose of 7.2 mg once-weekly for an additional 52 weeks until week 72. | Drug: Semaglutide<br>* Participants will receive once-weekly s.c. injections of semaglutide in escalating doses (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg, 2.4 mg and 7.2 mg) every fourth week. Treatment will be continued on the maintenance dose of 7.2 mg once-weekly for an additional 52 weeks. Injections may be administered in the thigh, abdomen, or upper arm, at any time of day irrespective of meals.<br>|
| Experimental: Semaglutide 2.4 mg<br>Participants will receive once-weekly s.c. injection of semaglutide in 20 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg, and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment will be continued on the maintenance dose of 2.4 mg once-weekly for an additional 52 weeks until week 72. | Drug: Semaglutide<br>* Participants will receive once-weekly s.c. injections of semaglutide in escalating doses (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg, and 2.4 mg) every fourth week. Treatment will be continued on the maintenance dose of 2.4 mg once-weekly for an additional 52 weeks. Injections may be administered in the thigh, abdomen, or upper arm, at any time of day irrespective of meals.<br>|
| Placebo Comparator: Placebo<br>Participants will receive once-weekly s.c. injection of placebo matched to semaglutide for 72 weeks. | Drug: Placebo<br>* Participants will receive once-weekly s.c. injection of placebo matched to semaglutide for 72 weeks. Injections may be administered in the thigh, abdomen, or upper arm, at any time of day irrespective of meals.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Semaglutide 7.2 mg versus Placebo: Relative change in body weight | Measured in percentage (%). | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Number of participants who achieve body weight reduction greater than or equal to (>=) 5% (yes/no) | Measured as count of participants. | From baseline (week 0) to end of treatment (week 72) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Semaglutide 7.2 mg versus Placebo: Number of participants who achieve body weight reduction >=10% (yes/no) | Measured as count of participants. | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Number of participants who achieve body weight reduction >=15% (yes/no) | Measured as count of participants. | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Number of participants who achieve body weight reduction >=20% (yes/no) | Measured as count of participants. | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Change in waist circumference | Measured in centimeters (cm). | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Change in glycated haemoglobin (HbA1c) | Measured in percentage (%). | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Change in body weight | Measured in kilograms (kg). | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Change in body mass index (BMI) | Measured in kilograms per square meter (kg/m^2). | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Change in systolic blood pressure | Measured in millimeters of mercury (mmHg). | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Change in diastolic blood pressure | Measured in mmHg. | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Change in total cholesterol | Measured in ratio to baseline. | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Change in high-density lipoprotein (HDL) cholesterol | Measured in ratio to baseline. | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Change in low-density lipoprotein (LDL) cholesterol | Measured in ratio to baseline. | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Change in very-low-density lipoprotein (VLDL) cholesterol | Measured in ratio to baseline. | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Change in triglycerides | Measured in ratio to baseline. | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Change in free fatty acids | Measured in ratio to baseline. | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Change in high-sensitivity c reactive protein (hsCRP) | Measured in ratio to baseline. | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Change in fasting plasma glucose | Measured in milligrams per deciliter (mg/dL). | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Change in fasting serum insulin | Measured in ratio to baseline. | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Number of participants with HbA1c less than (<) 7.0% (53 millimoles per mole [mmol/mol]) | Measured as count of participants. | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Number of participants with HbA1c less than or equal to (<=) 6.5 % (48 mmol/mol) | Measured as count of participants. | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Number of adverse events (AEs) | Measured as count of events. | From baseline (week 0) to end of study (week 81) | 
| Semaglutide 7.2 mg versus Placebo: Number of serious adverse events (SAEs) | Measured as count of events. | From baseline (week 0) to end of study (week 81) | 
| Semaglutide 7.2 mg versus Placebo: Change in pulse | Measured in beats per minute (bpm). | From baseline (week 0) to end of treatment (week 72) | 
| Semaglutide 7.2 mg versus Placebo: Number of treatment emergent severe or blood glucose confirmed symptomatic hypoglycaemic episodes | Measured as count of episodes. | From baseline (week 0) to end of study (week 81) | 
| Semaglutide 7.2 mg versus Semaglutide 2.4 mg: Number of AEs | Measured as count of events. | From baseline (week 0) to end of study (week 81) | 
| Semaglutide 7.2 mg versus Semaglutide 2.4 mg: Number of SAEs | Measured as count of events. | From baseline (week 0) to end of study (week 81) | 
| Semaglutide 7.2 mg versus Semaglutide 2.4 mg: Number of treatment emergent severe or blood glucose confirmed symptomatic hypoglycaemic episodes | Measured as count of episodes. | From baseline (week 0) to end of study (week 81) |