Effect and safety of semaglutide 2.4 mg once-weekly in subjects with overweight or obesity and type 2 diabetes

INTERVENTION: Product Name: Semaglutide B 3.0 mg/mL PDS290 Pharmaceutical Form: Solution for injection INN or Proposed INN: semaglutide CAS Number: 910463‐68‐2 Other descriptive name: SEMAGLUTIDE Concentration unit: mg/l milligram(s)/litre Concentration type: equal Concentration number: 3.0‐ Pharmaceutical form of the placebo: Solution for injection Route of administration of the placebo: Subcutaneous use Product Name: Semaglutide B 1.0 mg/mL PDS290 Pharmaceutical Form: Solution for injection INN or Proposed INN: Semaglutide CAS Number: 910463‐68‐2 Other descriptive name: SEMAGLUTIDE Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 1.0‐ Pharmaceutical form of the placebo: Solution for injection Route of administration of the placebo: Subcutaneous use Product Name: Semaglutide B 1.34 mg/mL PDS290 Pharmaceutical Form: Solution for injection INN or Proposed INN: Semaglutide CAS Number: 910463‐68‐2 Other descriptive name: SEMAGLUTIDE Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 1.34‐ Pharmaceutical form of the placebo: Solution for injection Route of administration of the placebo: Subcutaneous use CONDITION: 1. Obesity 2. Diabetes Mellitus, Type 2 ; MedDRA version: 20.0 Level: PT Classification code 10029883 Term: Obesity System Organ Class: 10027433 ‐ Metabolism and nutrition disorders ; MedDRA version: 20.1 Level: LLT Classification code 10045242 Term: Type II diabetes mellitus System Organ Class: 10027433 ‐ Metabolism and nutrition disorders Therapeutic area: Diseases [C] ‐ Nutritional and Metabolic Diseases [C18] PRIMARY OUTCOME: Main Objective: To compare the effect of semaglutide subcutaneous (s.c.) 2.4 mg once‐weekly versus semaglutide placebo I/II as an adjunct to a reduced‐calorie diet and increased physical activity in subjects with overweight or obesity and type 2 diabetes (T2D) on body weight. Primary end point(s): The primary endpoints addressing the primary objective:; 1. Change in body weight (%); 2. Subjects who achieve body weight reduction = 5% from baseline (week 0) (yes/no) Secondary Objective: To compare the effect of semaglutide s.c. 2.4 mg once‐weekly:; 1. versus semaglutide placebo I/II as an adjunct to a reduced‐calorie diet and increased physical activity in subjects with overweight or obesity and T2D on:; ‐ Cardiovascular risk factors; ‐ Clinical Outcome Assessments; ‐ Glycaemic control; 2. versus semaglutide s.c. 1.0 mg once‐weekly as an adjunct to reduced‐calorie diet and increased physical activity in subjects with overweight or obesity and T2D on factors related to body weight.; 3. To compare the effect of semaglutide s.c. 1.0 mg once‐weekly versus semaglutide placebo I/II as an adjunct to reduced‐calorie diet and increased physical activity in subjects with overweight or obesity and T2D on glycaemic control.; 4. To compare the safety and tolerability of semaglutide s.c. 2.4 mg once‐weekly versus semaglutide placebo I/II as an adjunct to reduced‐calorie diet and increased physical activity in subjects with overweight or obesity and T2D. Timepoint(s) of evaluation of this end point: 1. From baseline (week 0) to week 68; 2. After 68 weeks SECONDARY OUTCOME: Secondary end point(s): 1. Subjects who achieve (yes/no):; ‐ Body weight reduction = 10% from baseline (week 0); ‐ Body weight reduction = 15% from baseline (week 0); 2. Change in:; ‐ Waist circumference (cm); ‐ Body weight (%) (semaglutide s.c. 2.4 mg once‐weekly versus semaglutide s.c. 1.0; mg once‐weekly); ‐ Hemoglobin A1c (HbA1c) (%, mmol /mol); ‐ Systolic blood pressure (mmHg); ‐ Physical functioning score (SF‐36); ‐ Physical function domain (5‐items) score (IWQoL‐Lite for CT); 3. Change in:; ‐ Body weight (kg); ‐ BMI (kg/sqm); ‐ HbA1c (%, mmol/mol) (semaglutide s.c. 1.0 mg once‐weekly versus semaglutide placebo I/II); ‐ Fasting plasma glucose (FPG) (mg/dL); ‐ Fasting serum insulin (mIU/L); ‐ Diastolic blood pressure (mmHg); ‐ Lipids (mg/dL); ‐ Total cholesterol; ‐ High density lipoprotein (HDL) cholesterol; ‐ Low density lipoprotein (LDL) cholesterol; ‐ Very low density lipoprotein (VLDL) cholesterol; ‐ Free fatty acids (FFA); ‐ Triglycerides; ‐ High sensitivity C‐Reactive Protein (hsCRP) (mg/L); ‐ Plasminogen Activator Inhibitor‐1 (PAI‐1) Activity (AU/mL); ‐ SF‐36; ‐ role‐physical score; ‐ bodily pain score; ‐ general health score; ‐ vitality score; ‐ social functioning score; ‐ role‐emotional score; ‐ mental health score; ‐ physical component summary; ‐ mental component summary; ‐ IWQoL‐Lite for CT; ‐ pain/discomfort domain score; ‐ psychosocial domain score; ‐ total score; 4. Subjects who achieve (yes/no):; ‐ Responder definition value for SF‐36 physical functioning score; ‐ Responder definition value for IWQoL‐Lite for CT physical function domain (5‐items) score; ‐ HbA1c < 7.0% (53 mmol/mol); ‐ HbA1c = 6.5% (48 mmol/mol); 5. Number of treatment‐emergent adverse events (TEAEs) ; 6. Number of serious adverse events (SAEs) ; 7. Number of treatment emergent severe or blood glucose confirmed symptomatic; hypoglycaemia episodes ; 8. Change in:; ‐ Pulse (bpm); ‐ Amylase (U/L); ‐ Lipase (U/L); ‐ Calcitonin (ng/L) Timepoint(s) of evaluation of this end point: 1. After 68 weeks; 2. From baseline (week 0) to week 68; 3. From baseline (week 0) to week 68 ; 4. After 68 weeks; 5. – 7. From baseline (week 0) to week 75; 8. From baseline (week 0) to week 68 INCLUSION CRITERIA: ‐ Male or female, age = 18 years at the time of signing informed consent. ‐ Body Mass Index (BMI) = 27 kg/sqm ‐ History of at least one self‐reported unsuccessful dietary effort to lose body weight ‐ Diagnosed with T2D (HbA1c 7‐10% (53‐86 mmol/mol) (both inclusive)) = 180 days prior to the day of screening Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 960 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 240