STEP 2: Research Study Investigating How Well Semaglutide Works in People With Type 2 Diabetes Suffering From Overweight or Obesity

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03552757
• Collaborator: (none)
• Enrollment: 1,210
• Locations: 147
• Arms: 3
• Actual Duration (Months): 22.9
• Patients Per Site: 8.2
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This study will look at the change in the participant's body weight from the start to the end of the study. This is to compare the effect on body weight in people taking semaglutide (a new medicine) and people taking "dummy" medicine. In addition to taking the study medicine, the participant will have talks with study staff about healthy food choices, how to be more physically active and what else the participant can do to lose weight. Overweight and obesity is associated with an increased risk of type 2 diabetes. Therefore, weight loss has shown to have a beneficial impact on the blood sugar levels. The participant will either get semaglutide or "dummy" medicine - which treatment the participant get is decided by chance. The participant will need to take 2 injections at the same time once a week. The study medicine is injected with a thin needle in a skin fold in the stomach, thigh or upper arm. The study will last for about 1.5 years

Condition or Disease	Intervention/Treatment	Phase
Obesity; Overweight	Drug: Semaglutide 1.0 mg; Drug: Semaglutide 2.4 mg; Drug: Placebo I (Semaglutide); Drug: Placebo II (Semaglutide)	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1210 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Effect and Safety of Semaglutide 2.4 mg Once-weekly in Subjects With Overweight or Obesity and Type 2 Diabetes
• Actual Study Start Date: Jun 4, 2018
• Actual Primary Completion Date: Mar 24, 2020
• Actual Study Completion Date: May 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Semaglutide 1.0 mg Participants will receive semaglutide 1.0 mg and semaglutide placebo I during 68-week treatment period in addition to a reduced-calorie diet and increased physical activity.	Drug: Semaglutide 1.0 mg; Subcutaneous (s.c.) injections of semaglutide once weekly at an escalating doses (0.25 mg/week, 0.5 mg/week, 1.0 mg mg/week). The dose will be escalated to next level every 4 weeks.; Drug: Placebo I (Semaglutide); S.c. injections of placebo once weekly at a similar dose escalation manner as semaglutide 2.4 mg (placebo matched to semaglutide 0.25 mg/week, 0.5 mg/week, 1.0 mg mg/week, 1.7 mg/week and 2.4 mg/week). The dose will be escalated to next level every 4 weeks.
Experimental: Semaglutide 2.4 mg Participants will receive semaglutide 2.4 mg and semaglutide placebo II during 68-week treatment period in addition to a reduced-calorie diet and increased physical activity.	Drug: Semaglutide 2.4 mg; Subcutaneous injections of semaglutide once weekly at an escalating doses (0.25 mg/week, 0.5 mg/week, 1.0 mg mg/week, 1.7 mg/week and 2.4 mg/week). The dose will be escalated to next level every 4 weeks.; Drug: Placebo II (Semaglutide); S.c. injections of placebo once weekly at a similar dose escalation manner as semaglutide 1.0 mg (placebo matched to semaglutide 0.25 mg/week, 0.5 mg/week, 1.0 mg mg/week). The dose will be escalated to next level every 4 weeks.
Placebo Comparator: Semaglutide placebo I/II Participants will receive semaglutide placebo I and II during 68-week treatment period in addition to a reduced-calorie diet and increased physical activity.	Drug: Placebo I (Semaglutide); S.c. injections of placebo once weekly at a similar dose escalation manner as semaglutide 2.4 mg (placebo matched to semaglutide 0.25 mg/week, 0.5 mg/week, 1.0 mg mg/week, 1.7 mg/week and 2.4 mg/week). The dose will be escalated to next level every 4 weeks.; Drug: Placebo II (Semaglutide); S.c. injections of placebo once weekly at a similar dose escalation manner as semaglutide 1.0 mg (placebo matched to semaglutide 0.25 mg/week, 0.5 mg/week, 1.0 mg mg/week). The dose will be escalated to next level every 4 weeks.

Outcome Measures

Primary Outcome Measures

1. Change in Body Weight (%) - Semaglutide 2.4 mg Versus Placebo [Baseline (week 0) to week 68]

   Change in body weight (%) from baseline (week 0) to week 68 is presented. Results are based on the data from both in-trial and on-treatment observation periods. In-trial observation period: the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact (week 75). On-treatment observation period: the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 2-week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses.

2. Participants Who Achieve (Yes/no): Body Weight Reduction ≥5% - Semaglutide 2.4 mg Versus Placebo [At week 68]

   Number of participants who achieved weight reduction ≥5% of their baseline body weight (yes/no) at week 68 is presented. Results are based on the data from both in-trial and on-treatment observation periods. In-trial observation period: the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. On-treatment observation period: the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 2 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses.

Secondary Outcome Measures

1. Change in Body Weight (%) - Semaglutide 2.4 mg Versus Semaglutide 1.0 mg [Baseline (week 0) to week 68]

   Change in body weight (%) from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.

2. Participants Who Achieve (Yes/no): Body Weight Reduction ≥5% - Semaglutide 2.4 mg Versus Semaglutide 1.0 mg [At week 68]

   Number of participants who achieved weight reduction ≥5% of their baseline body weight (yes/no) at week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.

3. Change in Waist Circumference [Baseline (week 0) to week 68]

   Change in waist circumference from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.

4. Change in Body Weight (Kg) [Baseline (week 0) to week 68]

   Change in body weight (kg) from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.

5. Change in BMI [Baseline (week 0) to week 68]

   Change in body mass index (BMI) from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.

6. Participants Who Achieve (Yes/no): Body Weight Reduction ≥10% [At week 68]

   Number of participants who achieved weight reduction ≥10% of their baseline body weight (yes/no) at week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.

7. Participants Who Achieve (Yes/no): Body Weight Reduction ≥15% [At week 68]

   Number of participants who achieved weight reduction ≥15% of their baseline body weight (yes/no) at week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.

8. Participants Who Achieve (Yes/no): Body Weight Reduction ≥20% [At week 68]

   Number of participants who achieved weight reduction ≥20% of their baseline body weight (yes/no) at week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.

9. Change in HbA1c (%) [Baseline (week 0) to week 68]

   Change in glycated haemoglobin (HbA1c (%)) from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.

10. Change in HbA1c (mmol/Mol) [Baseline (week 0) to week 68]

    Change in HbA1c (mmol/mol) from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.

11. Change in FPG (mg/dL) [Baseline (week 0) to week 68]

    Change in fasting plasma glucose (FPG) from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.

12. Change in Fasting Serum Insulin [Baseline (week 0) to week 68]

    Change in fasting serum insulin from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.

13. Participants Who Achieve (Yes/no): HbA1c <7.0% (53 mmol/Mol) [At week 68]

    Number of participants who achieved HbA1c <7% (yes/no) at week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.

14. Participants Who Achieve (Yes/no): HbA1c ≤6.5% (48 mmol/Mol) [At week 68]

    Number of participants who achieved HbA1c ≤6.5% (yes/no) at week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.

15. Participants Who Achieve (Yes/no): Body Weight Reduction ≥10% and HbA1c <7.0% [At week 68]

    Number of participants who achieved weight reduction ≥10% of their baseline body weight and HbA1c <7.0% (yes/no) at week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.

16. Participants Who Achieve (Yes/no): Body Weight Reduction ≥15% and HbA1c <7.0% [At week 68]

    Number of participants who achieved weight reduction ≥15% of their baseline body weight and HbA1c <7.0% (yes/no) at week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.

17. Change in Systolic Blood Pressure [Baseline (week 0) to week 68]

    Change in systolic blood pressure from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.

18. Change in Diastolic Blood Pressure [Baseline (week 0) to week 68]

    Change in diastolic blood pressure from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.

19. Change in Total Cholesterol [Baseline (week 0) to week 68]

    Change in total cholesterol (measured in milligram per decilitre (mg/dL)) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.

20. Change in HDL Cholesterol [Baseline (week 0) to week 68]

    Change in high density lipoprotein (HDL; measured in mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.

21. Change in LDL Cholesterol [Baseline (week 0) to week 68]

    Change in low density lipoprotein (LDL; measured in mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.

22. Change in VLDL Cholesterol [Baseline (week 0) to week 68]

    Change in very low density lipoprotein (VLDL; measured in mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.

23. Change in Free Fatty Acids [Baseline (week 0) to week 68]

    Change in free fatty acids (measured in mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.

24. Change in Triglycerides [Baseline (week 0) to week 68]

    Change in triglycerides (measured in mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.

25. Change in hsCRP [Baseline (week 0) to week 68]

    Change in high sensitivity C-reactive protein (hsCRP; measured in milligram per ilitre (mg/L)) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.

26. Change in PAI-1 Activity [Baseline (week 0) to week 68]

    Change in Plasminogen Activator Inhibitor-1 (PAI-1; measured in arbritary units per millilitre (AU/mL)) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.

27. Change in Short Form 36 v2.0 Acute (SF-36) (Physical Functioning Score) [Baseline (week 0) to week 68]

    SF-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ questionnaire measured 8 domains of functional health and well-being as well as 2 component summary scores (physical component summary and mental component summary). This endpoint shows results for 'physical functioning domain'. The 0-100 scale scores from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. In the metric of norm-based scores, 50 and 10 corresponds to the mean and standard deviation respectively. Change from week 0 in the domain scores were evaluated at week 68. A positive change score indicates an improvement since baseline. Results are based on the data from in-trial observation period.

28. Change in SF-36 (All Scores Except Physical Functioning) [Baseline (week 0) to week 68]

    SF-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ questionnaire measured 8 domains of functional health and well-being as well as 2 component summary scores (physical component summary and mental component summary). This endpoint shows results for all the domains, except physical functioning. The 0-100 scale scores from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. In the metric of norm-based scores, 50 and 10 corresponds to the mean and standard deviation respectively. Change from week 0 in the domain scores and component summary scores were evaluated at week 68. A positive change score indicates an improvement since baseline. Results are based on the data from in-trial observation period.

29. Change in IWQOL-Lite for CT (Physical Function Domain (5-items) Score) [Baseline (week 0) to week 68]

    The Impact of Weight on Quality of Life Clinical Trials Version (IWQOL-Lite-CT) is designed to assess the impact of changes in weight on patients' quality of life within the context of clinical trials. IWQOL-Lite-CT is a 20-item questionnaire-based instrument used to assess the impact of body weight changes on participant's overall health-related quality of life (HRQoL). All IWQOL-Lite-CT composite scores range from 0 to 100, with higher scores reflecting better levels of functioning. This endpoint shows results for 'physical function domain'. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.

30. Change in IWQOL-Lite for CT (All Scores Except Physical Function) [Baseline (week 0) to week 68]

    The Impact of Weight on Quality of Life Clinical Trials Version (IWQOL-Lite-CT) is designed to assess the impact of changes in weight on patients' quality of life within the context of clinical trials. IWQOL-Lite-CT is a 20-item questionnaire-based instrument used to assess the impact of body weight changes on participant's overall health-related quality of life (HRQoL). All IWQOL-Lite-CT composite scores range from 0 to 100, with higher scores reflecting better levels of functioning. This endpoint shows results for 'physical and psychosocial domains, and for total'. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.

31. Participants Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score [At week 68]

    The observed number of participants experiencing a meaningful within participant improvement in SF-36 Physical function after 68 weeks was determined based on two thresholds. The threshold of 4.3 is the default generic responder threshold defined in SF-36 manual for a general population. The threshold of 3.7 is specific for overweight or obese population included in the study and calculated using patient global rating anchor questionnaires to reflect participants' own perspective based on Food and Drug Administration (FDA) recommendations. In the reported data, "Yes" infers the number of participants who have achieved an improvement in score greater than or equal to the threshold and "No" infers number of participants who have not achieved an improvement in score greater than or equal to the threshold. Endpoint was evaluated based on in-trial observation period which is the uninterrupted time interval from randomization (week 0) to last trial related subject-site contact (week 75).

32. Participants Who Achieve (Yes/no): Responder Definition Value for IWQOL-Lite for CT Physical Function Domain (5-items) Score [At week 68]

    The observed number of participants experiencing a meaningful within participant improvement in IWQOL-Lite-CT physical function after 68 weeks was determined based on two different thresholds. The threshold of 20 was a preliminary responder threshold based on earlier studies. The threshold of 14.6 is specific for the population with overweight or obesity included in the study and calculated using patient global rating anchor questionnaires to reflect participants' own perspective based on FDA recommendations. In the reported data, "Yes" infers the number of participants who have achieved an improvement in score greater than or equal to the threshold and "No" infers the number of participants who have not achieved an improvement in score greater than or equal to the threshold. The endpoint was evaluated based on the in-trial observation period which was defined as the uninterrupted time interval from randomization (week 0) to last trial related subject-site contact (week 75).

33. Number of TEAEs - Semaglutide 2.4 mg Versus Placebo [Week 0 to week 75]

    Adverse events (AEs) with onset during the on-treatment observation period were defined as treatment-emergent AEs (TEAEs). On-treatment observation period: the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 7 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least seven consecutive missed doses.

34. Number of SAEs - Semaglutide 2.4 mg Versus Placebo [Week 0 to week 75]

    Serious adverse event (SAE) results are based on the on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 7 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least seven consecutive missed doses.

35. Number of Treatment Emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemia Episodes - Semaglutide 2.4 mg Versus Placebo [Week 0 to week 75]

    Hypoglycaemic episodes with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 7 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least 7 consecutive missed doses. Severe hypoglycaemia: An episode requiring assistance of another person to actively administer carbohydrate, glucagon or take other corrective actions. plasma glucose (PG) concentrations may not be available during an event, but neurological recovery following the return of PG to normal is considered sufficient evidence that the event was induced by a low PG concentration. Blood glucose (BG) confirmed symptomatic hypoglycaemia: An episode that is BG confirmed by PG value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.

36. Change in Pulse - Semaglutide 2.4 mg Versus Placebo [Baseline (week 0) to week 68]

    Change in pulse from baseline (week 0) to week 68 is presented. Results are based on the data from on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 2 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses.

37. Change in Amylase - Semaglutide 2.4 mg Versus Placebo [Baseline (week 0) to week 68]

    Change in amylase (units/litre) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 2 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses.

38. Change in Lipase - Semaglutide 2.4 mg Versus Placebo [Baseline (week 0) to week 68]

    Change in lipase (units/litre) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 2 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses.

39. Change in Calcitonin - Semaglutide 2.4 mg Versus Placebo [Baseline (week 0) to week 68]

    Change in calcitonin (nanogram/litre) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 2 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female, age greater than or equal to 18 years at the time of signing informed consent

• Body Mass Index (BMI) greater than or equal to 27 kg/m^2 '

• History of at least one self-reported unsuccessful dietary effort to lose body weight

• Diagnosed with type 2 diabetes (haemoglobin A1c 7-10% (53-86 mmol/mol) (both inclusive)) 180 days or longer prior to the day of screening

Exclusion Criteria:

• A self-reported change in body weight greater than 5 kg (11 lbs) within 90 days before screening irrespective of medical records

• Renal impairment measured as estimated Glomerular Filtration Rate (eGFR) value of less than 30 mL/min/1.73 m^{2 (less than 60 ml/min/1.73 m}2 in subjects treated with Sodium-glucose Cotransporter 2 Inhibitors) according to chronic kidney disease (CKD)-Epidemiology Collaboration (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 pharmacologically pupil-dilated fundus examination performed by an ophthalmologist or an equally qualified health care provider (e.g. optometrist) within the past 90 days prior to screening or in the period between screening and randomisation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Buena Park	California	United States	90620
2	Novo Nordisk Investigational Site	Concord	California	United States	94520
3	Novo Nordisk Investigational Site	Fresno	California	United States	93720
4	Novo Nordisk Investigational Site	Lomita	California	United States	90717
5	Novo Nordisk Investigational Site	Los Angeles	California	United States	90057
6	Novo Nordisk Investigational Site	Mission Hills	California	United States	91345
7	Novo Nordisk Investigational Site	Spring Valley	California	United States	91978
8	Novo Nordisk Investigational Site	Tarzana	California	United States	91356-3551
9	Novo Nordisk Investigational Site	Golden	Colorado	United States	80401
10	Novo Nordisk Investigational Site	Clearwater	Florida	United States	33765
11	Novo Nordisk Investigational Site	Jacksonville	Florida	United States	32205
12	Novo Nordisk Investigational Site	Jacksonville	Florida	United States	32216
13	Novo Nordisk Investigational Site	Kissimmee	Florida	United States	34744
14	Novo Nordisk Investigational Site	Saint Petersburg	Florida	United States	33709
15	Novo Nordisk Investigational Site	Tampa	Florida	United States	33606
16	Novo Nordisk Investigational Site	Alpharetta	Georgia	United States	30022
17	Novo Nordisk Investigational Site	Atlanta	Georgia	United States	30318
18	Novo Nordisk Investigational Site	Roswell	Georgia	United States	30076
19	Novo Nordisk Investigational Site	Chicago	Illinois	United States	60607
20	Novo Nordisk Investigational Site	Chicago	Illinois	United States	60611
21	Novo Nordisk Investigational Site	Springfield	Illinois	United States	62711
22	Novo Nordisk Investigational Site	West Des Moines	Iowa	United States	50265
23	Novo Nordisk Investigational Site	Topeka	Kansas	United States	66606
24	Novo Nordisk Investigational Site	Lexington	Kentucky	United States	40503
25	Novo Nordisk Investigational Site	Louisville	Kentucky	United States	40213
26	Novo Nordisk Investigational Site	Minneapolis	Minnesota	United States	55416
27	Novo Nordisk Investigational Site	Olive Branch	Mississippi	United States	38654-3573
28	Novo Nordisk Investigational Site	Butte	Montana	United States	59701
29	Novo Nordisk Investigational Site	Lawrenceville	New Jersey	United States	08648
30	Novo Nordisk Investigational Site	Chapel Hill	North Carolina	United States	27514
31	Novo Nordisk Investigational Site	Greensboro	North Carolina	United States	27408
32	Novo Nordisk Investigational Site	Greenville	North Carolina	United States	27834
33	Novo Nordisk Investigational Site	Hickory	North Carolina	United States	28601
34	Novo Nordisk Investigational Site	Salisbury	North Carolina	United States	28144
35	Novo Nordisk Investigational Site	Wilmington	North Carolina	United States	28401
36	Novo Nordisk Investigational Site	Wadsworth	Ohio	United States	44281
37	Novo Nordisk Investigational Site	Anderson	South Carolina	United States	29621
38	Novo Nordisk Investigational Site	Mount Pleasant	South Carolina	United States	29464
39	Novo Nordisk Investigational Site	Bristol	Tennessee	United States	37620
40	Novo Nordisk Investigational Site	Nashville	Tennessee	United States	37212
41	Novo Nordisk Investigational Site	Austin	Texas	United States	78749
42	Novo Nordisk Investigational Site	Dallas	Texas	United States	75230
43	Novo Nordisk Investigational Site	Dallas	Texas	United States	75231
44	Novo Nordisk Investigational Site	Dallas	Texas	United States	75251
45	Novo Nordisk Investigational Site	Dallas	Texas	United States	75390-9302
46	Novo Nordisk Investigational Site	Houston	Texas	United States	77079
47	Novo Nordisk Investigational Site	Shavano Park	Texas	United States	78231
48	Novo Nordisk Investigational Site	Saint George	Utah	United States	84790
49	Novo Nordisk Investigational Site	Winchester	Virginia	United States	22601
50	Novo Nordisk Investigational Site	Olympia	Washington	United States	98502
51	Novo Nordisk Investigational Site	Caba		Argentina	C1060ABA
52	Novo Nordisk Investigational Site	Chacabuco		Argentina	B6740ELF
53	Novo Nordisk Investigational Site	Córdoba		Argentina	X5016KEH
54	Novo Nordisk Investigational Site	Mendoza		Argentina	5500
55	Novo Nordisk Investigational Site	Santiago del Estero		Argentina	G4200
56	Novo Nordisk Investigational Site	Calgary	Alberta	Canada	T2V 4J2
57	Novo Nordisk Investigational Site	Mount Pearl	Newfoundland and Labrador	Canada	A1N 1W7
58	Novo Nordisk Investigational Site	Concord	Ontario	Canada	L4K 4M2
59	Novo Nordisk Investigational Site	London	Ontario	Canada	N5W 6A2
60	Novo Nordisk Investigational Site	Stoney Creek	Ontario	Canada	L8J 0B6
61	Novo Nordisk Investigational Site	Toronto	Ontario	Canada	M4G 3E8
62	Novo Nordisk Investigational Site	Toronto	Ontario	Canada	M9V 4B4
63	Novo Nordisk Investigational Site	Montreal	Quebec	Canada	H1M 1B1
64	Novo Nordisk Investigational Site	Montreal	Quebec	Canada	H4T 1Z9
65	Novo Nordisk Investigational Site	St-Marc-des-Carrières	Quebec	Canada	G0A 4B0
66	Novo Nordisk Investigational Site	Essen		Germany	45136
67	Novo Nordisk Investigational Site	Falkensee		Germany	14612
68	Novo Nordisk Investigational Site	Hamburg		Germany	22041
69	Novo Nordisk Investigational Site	Hamburg		Germany	22607
70	Novo Nordisk Investigational Site	Lingen		Germany	49808
71	Novo Nordisk Investigational Site	Münster		Germany	48145
72	Novo Nordisk Investigational Site	Rehlingen-Siersburg		Germany	66780
73	Novo Nordisk Investigational Site	Schweinfurt		Germany	97421
74	Novo Nordisk Investigational Site	Stuttgart		Germany	70378
75	Novo Nordisk Investigational Site	Athens		Greece	GR-11527
76	Novo Nordisk Investigational Site	Haidari-Athens		Greece	GR-12462
77	Novo Nordisk Investigational Site	Thessaloniki		Greece	GR-54636
78	Novo Nordisk Investigational Site	Thessaloniki		Greece	GR-54643
79	Novo Nordisk Investigational Site	Thessaloniki		Greece	GR-57001
80	Novo Nordisk Investigational Site	Thessaloniki		Greece	GR-57010
81	Novo Nordisk Investigational Site	Ahmedabad	Gujarat	India	380007
82	Novo Nordisk Investigational Site	Ahmedabad	Gujarat	India	380054
83	Novo Nordisk Investigational Site	Bangalore	Karnataka	India	560054
84	Novo Nordisk Investigational Site	Kochi	Kerala	India	682041
85	Novo Nordisk Investigational Site	Mumbai	Maharashtra	India	400008
86	Novo Nordisk Investigational Site	Mumbai	Maharashtra	India	400012
87	Novo Nordisk Investigational Site	Pune	Maharashtra	India	411013
88	Novo Nordisk Investigational Site	New Dehli	New Delhi	India	110029
89	Novo Nordisk Investigational Site	Jaipur	Rajasthan	India	302017
90	Novo Nordisk Investigational Site	Chennai	Tamil Nadu	India	600 013
91	Novo Nordisk Investigational Site	Chennai	Tamil Nadu	India	600086
92	Novo Nordisk Investigational Site	Coimbatore	Tamil Nadu	India	641009
93	Novo Nordisk Investigational Site	Kolkata	West Bengal	India	700054
94	Novo Nordisk Investigational Site	Kolkata	West Bengal	India	700064
95	Novo Nordisk Investigational Site	New Delhi		India	110088
96	Novo Nordisk Investigational Site	Secunderabad		India	500 003
97	Novo Nordisk Investigational Site	Chiba-shi, Chiba		Japan	260-0804
98	Novo Nordisk Investigational Site	Chuo-ku, Tokyo		Japan	103-0002
99	Novo Nordisk Investigational Site	Fukuoka-shi, Fukuoka		Japan	812-8582
100	Novo Nordisk Investigational Site	Hokkaido		Japan	060-0062
101	Novo Nordisk Investigational Site	Hokkaido		Japan	062-0007
102	Novo Nordisk Investigational Site	Ibaraki		Japan	311-0113
103	Novo Nordisk Investigational Site	Kashiwara-shi, Osaka		Japan	582-0005
104	Novo Nordisk Investigational Site	Mitaka-shi, Tokyo		Japan	181-0013
105	Novo Nordisk Investigational Site	Osaka		Japan	565-0871
106	Novo Nordisk Investigational Site	Osaka		Japan	569-1045
107	Novo Nordisk Investigational Site	Sapporo-shi, Hokkaido		Japan	060-0001
108	Novo Nordisk Investigational Site	Tochigi		Japan	323-0022
109	Novo Nordisk Investigational Site	San Juan		Puerto Rico	00921
110	Novo Nordisk Investigational Site	Barnaul		Russian Federation	656043
111	Novo Nordisk Investigational Site	Moscow		Russian Federation	117036
112	Novo Nordisk Investigational Site	Moscow		Russian Federation	123448
113	Novo Nordisk Investigational Site	Moscow		Russian Federation	127486
114	Novo Nordisk Investigational Site	Moscow		Russian Federation	129110
115	Novo Nordisk Investigational Site	Saint Petersburg		Russian Federation	194291
116	Novo Nordisk Investigational Site	Saint-Petersburg		Russian Federation	194354
117	Novo Nordisk Investigational Site	Saint-Petersburg		Russian Federation	199226
118	Novo Nordisk Investigational Site	Tomsk		Russian Federation	634050
119	Novo Nordisk Investigational Site	Johannesburg	Gauteng	South Africa	2001
120	Novo Nordisk Investigational Site	Johannesburg	Gauteng	South Africa	2013
121	Novo Nordisk Investigational Site	Pretoria	Gauteng	South Africa	0181
122	Novo Nordisk Investigational Site	Pretoria	Gauteng	South Africa	0184
123	Novo Nordisk Investigational Site	Durban	KwaZulu-Natal	South Africa	4001
124	Novo Nordisk Investigational Site	Brits	North West	South Africa	0250
125	Novo Nordisk Investigational Site	Almeria		Spain	04009
126	Novo Nordisk Investigational Site	Córdoba		Spain	14004
127	Novo Nordisk Investigational Site	Madrid		Spain	28040
128	Novo Nordisk Investigational Site	Málaga		Spain	29010
129	Novo Nordisk Investigational Site	San Cristóbal de La Laguna		Spain	38320
130	Novo Nordisk Investigational Site	Sevilla		Spain	41003
131	Novo Nordisk Investigational Site	Sevilla		Spain	41010
132	Novo Nordisk Investigational Site	Valladolid		Spain	47010
133	Novo Nordisk Investigational Site	Dubai		United Arab Emirates	22241
134	Novo Nordisk Investigational Site	Dubai		United Arab Emirates	4545
135	Novo Nordisk Investigational Site	Dubai		United Arab Emirates	9115
136	Novo Nordisk Investigational Site	Hatta		United Arab Emirates	7272
137	Novo Nordisk Investigational Site	Umm Al Quwain		United Arab Emirates	24
138	Novo Nordisk Investigational Site	Chester		United Kingdom	CH2 1UL
139	Novo Nordisk Investigational Site	Crewe		United Kingdom	CW5 5NX
140	Novo Nordisk Investigational Site	Glasgow		United Kingdom	G31 2ER
141	Novo Nordisk Investigational Site	Harrogate, North Yorkshire		United Kingdom	HG2 7SX
142	Novo Nordisk Investigational Site	Leicester		United Kingdom	LE5 4PW
143	Novo Nordisk Investigational Site	Middlesbrough		United Kingdom	TS4 3BW
144	Novo Nordisk Investigational Site	Soham		United Kingdom	CB7 5JD
145	Novo Nordisk Investigational Site	Stevenage		United Kingdom	SG1 4AB
146	Novo Nordisk Investigational Site	Watford		United Kingdom	WD25 7NL
147	Novo Nordisk Investigational Site	Wellingborough		United Kingdom	NN8 4RW

Sponsors and Collaborators

• Novo Nordisk A/S

Investigators

• Study Director: Clinical Reporting Anchor and Disclosure (1452), Novo Nordisk A/S

Study Documents (Full-Text)

• Study Protocol - Nov 8, 2018
• Statistical Analysis Plan - May 19, 2020

More Information

Publications

• Kushner RF, Calanna S, Davies M, Dicker D, Garvey WT, Goldman B, Lingvay I, Thomsen M, Wadden TA, Wharton S, Wilding JPH, Rubino D. Semaglutide 2.4 mg for the Treatment of Obesity: Key Elements of the STEP Trials 1 to 5. Obesity (Silver Spring). 2020 Jun;28(6):1050-1061. doi: 10.1002/oby.22794.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT03552757
• Other Study ID Numbers: NN9536-4374; U1111-1200-8148; 2017-003414-10
• First Posted: Jun 12, 2018
• Last Update Posted: Nov 9, 2021
• Last Verified: Nov 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Obesity; Overweight

Study Results

Participant Flow

Recruitment Details	The trial was conducted at 149 sites in 12 countries as follows: Argentina (5 sites), Canada (10 sites), Germany (9 sites), Greece (6 sites), India (18 sites), Japan (12 sites), Russian Federation (9 sites), South Africa (6 sites), Spain (8 sites), United Arab Emirates (5 sites), United Kingdom (10 sites) and United States (51 sites).
Pre-assignment Detail	Participants were randomised in 1:1:1 ratio to receive either 'semaglutide 2.4 milligram (mg) and placebo II (placebo matched to semaglutide 1.0 mg) once weekly', 'semaglutide 1.0 mg and placebo I (placebo matched to semaglutide 2.4 mg) once weekly' or 'placebo I and placebo II once weekly'.

Arm/Group Title	Semaglutide 1.0 mg	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly subcutaneous (s.c; under the skin) semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Period Title: Overall Study
STARTED	403	404	403
Exposed	402	403	402
Full Analysis Set (FAS)	403	404	403
Safety Analysis Set (SAS)	402	403	402
COMPLETED	390	391	383
NOT COMPLETED	13	13	20

Baseline Characteristics

Arm/Group Title	Semaglutide 1.0 mg	Semaglutide 2.4 mg	Placebo	Total
Arm/Group Description	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Total of all reporting groups
Overall Participants	403	404	403	1210
Age (Year) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Year]	56 (10)	55 (11)	55 (11)	55 (11)
Sex: Female, Male (Count of Participants)
Female	203 50.4%	223 55.2%	190 47.1%	616 50.9%
Male	200 49.6%	181 44.8%	213 52.9%	594 49.1%
Race/Ethnicity, Customized (Count of Participants)
White	272 67.5%	237 58.7%	242 60%	751 62.1%
Asian	97 24.1%	112 27.7%	108 26.8%	317 26.2%
Black or African American	28 6.9%	35 8.7%	37 9.2%	100 8.3%
Other	6 1.5%	16 4%	13 3.2%	35 2.9%
American Indian or Alaska Native	0 0%	4 1%	2 0.5%	6 0.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	1 0.2%	1 0.1%
Not Applicable	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
Not Hispanic or Latino	344 85.4%	357 88.4%	354 87.8%	1055 87.2%
Hispanic or Latino	59 14.6%	47 11.6%	49 12.2%	155 12.8%
Not Applicable	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Change in Body Weight (%) - Semaglutide 2.4 mg Versus Placebo
Description	Change in body weight (%) from baseline (week 0) to week 68 is presented. Results are based on the data from both in-trial and on-treatment observation periods. In-trial observation period: the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact (week 75). On-treatment observation period: the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 2-week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses.
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

Overall number of participants analysed = FAS which comprised all randomised participants. Number analysed = number of participants with available data.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Measure Participants	404	403
In-trial observation period	-9.9 (8.0)	-3.3 (5.5)
On-treatment observation period	-10.7 (7.8)	-3.1 (5.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Semaglutide 2.4 mg, Placebo
	Comments	Results are based on the data from in-trial observation period. Week 68 responses were analysed using an analysis of covariance model (ANCOVA) with randomised treatment, stratification groups (oral anti-diabetic (OAD) treatment status and HbA1c category at screening) and the interaction between stratification groups as factors and baseline body weight as covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-6.21
	Confidence Interval	(2-Sided) 95%; -7.28 to -5.15
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Semaglutide 2.4 mg, Placebo
	Comments	Results are based on the data from on-treatment observation period. All responses prior to first discontinuation of treatment (or initiation of other anti-obesity medication or bariatric surgery) were included in a mixed model for repeated measurements (MMRM) with randomised treatment, stratification groups (OAD treatment status and HbA1c category at screening) and the interaction between stratification groups as factors and baseline body weight as covariate, all nested within visit.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-7.57
	Confidence Interval	(2-Sided) 95%; -8.56 to -6.58
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Participants Who Achieve (Yes/no): Body Weight Reduction ≥5% - Semaglutide 2.4 mg Versus Placebo
Description	Number of participants who achieved weight reduction ≥5% of their baseline body weight (yes/no) at week 68 is presented. Results are based on the data from both in-trial and on-treatment observation periods. In-trial observation period: the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact. On-treatment observation period: the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 2 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses.
Time Frame	At week 68

Outcome Measure Data

Analysis Population Description

Overall number of participants analysed = FAS which comprised all randomised participants. Number analysed = number of participants with available data.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Measure Participants	404	403
Yes	267 66.3%	107 26.5%
No	121 30%	269 66.6%
Yes	257 63.8%	94 23.3%
No	94 23.3%	246 60.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Semaglutide 2.4 mg, Placebo
	Comments	Results are based on the data from in-trial observation period. Week 68 responses were analysed using a binary logistic regression model with randomised treatment, stratification groups (OAD treatment status and HbA1c category at screening) and the interaction between stratification groups as factors and baseline body weight as covariate.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	4.88
	Confidence Interval	(2-Sided) 95%; 3.58 to 6.64
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Semaglutide 2.4 mg, Placebo
	Comments	Results are based on the data from on-treatment observation period. All responses prior to first discontinuation of treatment (or initiation of other anti-obesity medication or bariatric surgery) were included in a MMRM with randomised treatment, stratification groups (OAD treatment status and HbA1c category at screening) and the interaction between stratification groups as factors and baseline body weight as covariate, all nested within visit.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	8.69
	Confidence Interval	(2-Sided) 95%; 6.31 to 11.97
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change in Body Weight (%) - Semaglutide 2.4 mg Versus Semaglutide 1.0 mg
Description	Change in body weight (%) from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.

Arm/Group Title	Semaglutide 2.4 mg	Semaglutide 1.0 mg
Arm/Group Description	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Measure Participants	388	380
Mean (Standard Deviation) [Percentage point of body weight]	-9.9 (8.0)	-7.2 (6.6)

4. Secondary Outcome

Title	Participants Who Achieve (Yes/no): Body Weight Reduction ≥5% - Semaglutide 2.4 mg Versus Semaglutide 1.0 mg
Description	Number of participants who achieved weight reduction ≥5% of their baseline body weight (yes/no) at week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time Frame	At week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.

Arm/Group Title	Semaglutide 2.4 mg	Semaglutide 1.0 mg
Arm/Group Description	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Measure Participants	388	380
Yes	267 66.3%	217 53.7%
No	121 30%	163 40.3%

5. Secondary Outcome

Title	Change in Waist Circumference
Description	Change in waist circumference from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Measure Participants	380	387	375
Mean (Standard Deviation) [Centimetre (cm)]	-6.9 (6.8)	-9.7 (8.1)	-4.3 (6.5)

6. Secondary Outcome

Title	Change in Body Weight (Kg)
Description	Change in body weight (kg) from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Measure Participants	380	388	376
Mean (Standard Deviation) [Kilogram (kg)]	-7.1 (6.7)	-9.9 (8.5)	-3.4 (6.2)

7. Secondary Outcome

Title	Change in BMI
Description	Change in body mass index (BMI) from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Measure Participants	380	388	376
Mean (Standard Deviation) [kilogram per square meter (kg/m^2)]	-2.6 (2.4)	-3.6 (3.1)	-1.2 (2.1)

8. Secondary Outcome

Title	Participants Who Achieve (Yes/no): Body Weight Reduction ≥10%
Description	Number of participants who achieved weight reduction ≥10% of their baseline body weight (yes/no) at week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time Frame	At week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Measure Participants	380	388	376
Yes	109 27%	177 43.8%	31 7.7%
No	271 67.2%	211 52.2%	345 85.6%

9. Secondary Outcome

Title	Participants Who Achieve (Yes/no): Body Weight Reduction ≥15%
Description	Number of participants who achieved weight reduction ≥15% of their baseline body weight (yes/no) at week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time Frame	At week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Measure Participants	380	388	376
Yes	52 12.9%	100 24.8%	12 3%
No	328 81.4%	288 71.3%	364 90.3%

10. Secondary Outcome

Title	Participants Who Achieve (Yes/no): Body Weight Reduction ≥20%
Description	Number of participants who achieved weight reduction ≥20% of their baseline body weight (yes/no) at week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time Frame	At week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Measure Participants	380	388	376
Yes	18 4.5%	51 12.6%	6 1.5%
No	362 89.8%	337 83.4%	370 91.8%

11. Secondary Outcome

Title	Change in HbA1c (%)
Description	Change in glycated haemoglobin (HbA1c (%)) from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Measure Participants	376	381	374
Mean (Standard Deviation) [Percentage point of HbA1c]	-1.5 (1.1)	-1.7 (1.2)	-0.3 (1.3)

12. Secondary Outcome

Title	Change in HbA1c (mmol/Mol)
Description	Change in HbA1c (mmol/mol) from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Measure Participants	376	381	374
Mean (Standard Deviation) [millimoles per mole (mmol/mol)]	-16.9 (12.3)	-18.7 (13.0)	-3.4 (14.3)

13. Secondary Outcome

Title	Change in FPG (mg/dL)
Description	Change in fasting plasma glucose (FPG) from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Measure Participants	367	375	370
Mean (Standard Deviation) [milligrams per deciliter (mg/dL)]	-36.5 (45.1)	-37.9 (45.9)	-2.3 (53.1)

14. Secondary Outcome

Title	Change in Fasting Serum Insulin
Description	Change in fasting serum insulin from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Measure Participants	352	360	351
Geometric Mean (Geometric Coefficient of Variation) [Picomoles per litre (pmol/L)]	0.94 (59.8)	0.90 (65.4)	0.93 (53.6)

15. Secondary Outcome

Title	Participants Who Achieve (Yes/no): HbA1c <7.0% (53 mmol/Mol)
Description	Number of participants who achieved HbA1c <7% (yes/no) at week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time Frame	At week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Measure Participants	376	381	374
Yes	272 67.5%	299 74%	99 24.6%
No	104 25.8%	82 20.3%	275 68.2%

16. Secondary Outcome

Title	Participants Who Achieve (Yes/no): HbA1c ≤6.5% (48 mmol/Mol)
Description	Number of participants who achieved HbA1c ≤6.5% (yes/no) at week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time Frame	At week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Measure Participants	376	381	374
Yes	226 56.1%	257 63.6%	58 14.4%
No	150 37.2%	124 30.7%	316 78.4%

17. Secondary Outcome

Title	Participants Who Achieve (Yes/no): Body Weight Reduction ≥10% and HbA1c <7.0%
Description	Number of participants who achieved weight reduction ≥10% of their baseline body weight and HbA1c <7.0% (yes/no) at week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time Frame	At week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Measure Participants	376	381	374
Yes	105 26.1%	170 42.1%	25 6.2%
No	271 67.2%	211 52.2%	349 86.6%

18. Secondary Outcome

Title	Participants Who Achieve (Yes/no): Body Weight Reduction ≥15% and HbA1c <7.0%
Description	Number of participants who achieved weight reduction ≥15% of their baseline body weight and HbA1c <7.0% (yes/no) at week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time Frame	At week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Measure Participants	376	381	374
Yes	49 12.2%	98 24.3%	11 2.7%
No	327 81.1%	283 70%	363 90.1%

19. Secondary Outcome

Title	Change in Systolic Blood Pressure
Description	Change in systolic blood pressure from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Measure Participants	379	387	376
Mean (Standard Deviation) [Millimetre of mercury (mmHg)]	-3 (15)	-4 (14)	0 (15)

20. Secondary Outcome

Title	Change in Diastolic Blood Pressure
Description	Change in diastolic blood pressure from baseline (week 0) to week 68 is presented. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Measure Participants	379	387	376
Mean (Standard Deviation) [Millimetre of mercury (mmHg)]	-1 (9)	-2 (9)	-1 (9)

21. Secondary Outcome

Title	Change in Total Cholesterol
Description	Change in total cholesterol (measured in milligram per decilitre (mg/dL)) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Measure Participants	372	380	373
Geometric Mean (Geometric Coefficient of Variation) [Ratio of total cholesterol]	0.97 (20.1)	0.99 (17.9)	1.00 (18.9)

22. Secondary Outcome

Title	Change in HDL Cholesterol
Description	Change in high density lipoprotein (HDL; measured in mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Measure Participants	372	375	369
Geometric Mean (Geometric Coefficient of Variation) [Ratio of HDL cholesterol]	1.06 (16.0)	1.07 (15.7)	1.04 (15.3)

23. Secondary Outcome

Title	Change in LDL Cholesterol
Description	Change in low density lipoprotein (LDL; measured in mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Measure Participants	372	380	373
Geometric Mean (Geometric Coefficient of Variation) [Ratio of LDL cholesterol]	0.99 (37.5)	1.00 (30.9)	1.00 (28.9)

24. Secondary Outcome

Title	Change in VLDL Cholesterol
Description	Change in very low density lipoprotein (VLDL; measured in mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Measure Participants	372	380	373
Geometric Mean (Geometric Coefficient of Variation) [Ratio of VLDL cholesterol]	0.82 (42.1)	0.80 (42.0)	0.92 (40.5)

25. Secondary Outcome

Title	Change in Free Fatty Acids
Description	Change in free fatty acids (measured in mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Measure Participants	353	361	354
Geometric Mean (Geometric Coefficient of Variation) [Ratio of free fatty acids]	0.85 (61.4)	0.84 (68.7)	1.01 (62.3)

26. Secondary Outcome

Title	Change in Triglycerides
Description	Change in triglycerides (measured in mg/dL) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Measure Participants	372	380	373
Geometric Mean (Geometric Coefficient of Variation) [Ratio of triglycerides]	0.81 (44.5)	0.79 (43.8)	0.92 (44.5)

27. Secondary Outcome

Title	Change in hsCRP
Description	Change in high sensitivity C-reactive protein (hsCRP; measured in milligram per ilitre (mg/L)) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Measure Participants	372	380	373
Geometric Mean (Geometric Coefficient of Variation) [Ratio of hsCRP]	0.59 (115.7)	0.50 (125.7)	0.84 (90.9)

28. Secondary Outcome

Title	Change in PAI-1 Activity
Description	Change in Plasminogen Activator Inhibitor-1 (PAI-1; measured in arbritary units per millilitre (AU/mL)) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Measure Participants	334	353	336
Geometric Mean (Geometric Coefficient of Variation) [Ratio of PAI-1 activity]	1.21 (73.7)	1.06 (80.8)	1.42 (68.9)

29. Secondary Outcome

Title	Change in Short Form 36 v2.0 Acute (SF-36) (Physical Functioning Score)
Description	SF-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ questionnaire measured 8 domains of functional health and well-being as well as 2 component summary scores (physical component summary and mental component summary). This endpoint shows results for 'physical functioning domain'. The 0-100 scale scores from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. In the metric of norm-based scores, 50 and 10 corresponds to the mean and standard deviation respectively. Change from week 0 in the domain scores were evaluated at week 68. A positive change score indicates an improvement since baseline. Results are based on the data from in-trial observation period.
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Measure Participants	370	376	365
Mean (Standard Deviation) [Score on a scale]	2.1 (6.8)	2.8 (7.7)	0.8 (7.0)

30. Secondary Outcome

Title	Change in SF-36 (All Scores Except Physical Functioning)
Description	SF-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ questionnaire measured 8 domains of functional health and well-being as well as 2 component summary scores (physical component summary and mental component summary). This endpoint shows results for all the domains, except physical functioning. The 0-100 scale scores from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. In the metric of norm-based scores, 50 and 10 corresponds to the mean and standard deviation respectively. Change from week 0 in the domain scores and component summary scores were evaluated at week 68. A positive change score indicates an improvement since baseline. Results are based on the data from in-trial observation period.
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Measure Participants	370	376	365
Role-Physical	0.6 (6.9)	0.8 (7.4)	0.0 (7.1)
Bodily Pain	0.4 (8.3)	0.3 (9.0)	-0.4 (8.6)
General Health	1.7 (7.2)	2.2 (7.3)	0.6 (7.5)
Vitality	-0.1 (7.8)	0.8 (7.9)	-0.9 (7.9)
Social Functioning	-0.3 (6.6)	0.2 (6.6)	-0.7 (7.4)
Role-Emotional	-0.4 (7.3)	-0.4 (7.7)	-1.1 (7.8)
Mental Health	-0.9 (7.5)	-0.4 (6.9)	-1.6 (7.5)
Physical component summary	1.9 (6.4)	2.3 (7.2)	0.9 (6.6)
Mental component summary	-1.4 (7.4)	-0.9 (6.9)	-1.8 (7.6)

31. Secondary Outcome

Title	Change in IWQOL-Lite for CT (Physical Function Domain (5-items) Score)
Description	The Impact of Weight on Quality of Life Clinical Trials Version (IWQOL-Lite-CT) is designed to assess the impact of changes in weight on patients' quality of life within the context of clinical trials. IWQOL-Lite-CT is a 20-item questionnaire-based instrument used to assess the impact of body weight changes on participant's overall health-related quality of life (HRQoL). All IWQOL-Lite-CT composite scores range from 0 to 100, with higher scores reflecting better levels of functioning. This endpoint shows results for 'physical function domain'. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Measure Participants	369	376	365
Mean (Standard Deviation) [Score on a scale]	8.5 (18.8)	11.4 (20.8)	4.9 (20.4)

32. Secondary Outcome

Title	Change in IWQOL-Lite for CT (All Scores Except Physical Function)
Description	The Impact of Weight on Quality of Life Clinical Trials Version (IWQOL-Lite-CT) is designed to assess the impact of changes in weight on patients' quality of life within the context of clinical trials. IWQOL-Lite-CT is a 20-item questionnaire-based instrument used to assess the impact of body weight changes on participant's overall health-related quality of life (HRQoL). All IWQOL-Lite-CT composite scores range from 0 to 100, with higher scores reflecting better levels of functioning. This endpoint shows results for 'physical and psychosocial domains, and for total'. Results are based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact.
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Measure Participants	369	376	365
Physical	7.6 (18.0)	11.0 (19.6)	4.4 (19.1)
Psychosocial	8.6 (15.7)	9.6 (16.7)	5.6 (16.5)
Total	8.2 (14.8)	10.1 (15.9)	5.2 (15.5)

33. Secondary Outcome

Title	Participants Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score
Description	The observed number of participants experiencing a meaningful within participant improvement in SF-36 Physical function after 68 weeks was determined based on two thresholds. The threshold of 4.3 is the default generic responder threshold defined in SF-36 manual for a general population. The threshold of 3.7 is specific for overweight or obese population included in the study and calculated using patient global rating anchor questionnaires to reflect participants' own perspective based on Food and Drug Administration (FDA) recommendations. In the reported data, "Yes" infers the number of participants who have achieved an improvement in score greater than or equal to the threshold and "No" infers number of participants who have not achieved an improvement in score greater than or equal to the threshold. Endpoint was evaluated based on in-trial observation period which is the uninterrupted time interval from randomization (week 0) to last trial related subject-site contact (week 75).
Time Frame	At week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Measure Participants	370	376	365
Yes (with threshold 4.3)	88 21.8%	111 27.5%	68 16.9%
No (with threshold 4.3)	282 70%	265 65.6%	297 73.7%
Yes (with threshold 3.7)	130 32.3%	158 39.1%	102 25.3%
No (with threshold 3.7)	240 59.6%	218 54%	263 65.3%

34. Secondary Outcome

Title	Participants Who Achieve (Yes/no): Responder Definition Value for IWQOL-Lite for CT Physical Function Domain (5-items) Score
Description	The observed number of participants experiencing a meaningful within participant improvement in IWQOL-Lite-CT physical function after 68 weeks was determined based on two different thresholds. The threshold of 20 was a preliminary responder threshold based on earlier studies. The threshold of 14.6 is specific for the population with overweight or obesity included in the study and calculated using patient global rating anchor questionnaires to reflect participants' own perspective based on FDA recommendations. In the reported data, "Yes" infers the number of participants who have achieved an improvement in score greater than or equal to the threshold and "No" infers the number of participants who have not achieved an improvement in score greater than or equal to the threshold. The endpoint was evaluated based on the in-trial observation period which was defined as the uninterrupted time interval from randomization (week 0) to last trial related subject-site contact (week 75).
Time Frame	At week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomised participants. 'Overall Number of Participants Analysed' = participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Measure Participants	369	376	365
Yes (with threshold 20)	107 26.6%	131 32.4%	83 20.6%
No (with threshold 20)	262 65%	245 60.6%	282 70%
Yes (with threshold 14.6)	144 35.7%	160 39.6%	113 28%
No (with threshold 14.6)	225 55.8%	216 53.5%	252 62.5%

35. Secondary Outcome

Title	Number of TEAEs - Semaglutide 2.4 mg Versus Placebo
Description	Adverse events (AEs) with onset during the on-treatment observation period were defined as treatment-emergent AEs (TEAEs). On-treatment observation period: the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 7 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least seven consecutive missed doses.
Time Frame	Week 0 to week 75

Outcome Measure Data

Analysis Population Description

Safety analysis set (SAS) included all randomised participants exposed to at least one dose of randomised treatment. 'Overall Number of Participants Analysed' = participants with available data.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Measure Participants	403	402
Number [Events]	2197	1388

36. Secondary Outcome

Title	Number of SAEs - Semaglutide 2.4 mg Versus Placebo
Description	Serious adverse event (SAE) results are based on the on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 7 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least seven consecutive missed doses.
Time Frame	Week 0 to week 75

Outcome Measure Data

Analysis Population Description

SAS included all randomised participants exposed to at least one dose of randomised treatment. 'Overall Number of Participants Analysed' = participants with available data.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Measure Participants	403	402
Number [Events]	71	53

37. Secondary Outcome

Title	Number of Treatment Emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemia Episodes - Semaglutide 2.4 mg Versus Placebo
Description	Hypoglycaemic episodes with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 7 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least 7 consecutive missed doses. Severe hypoglycaemia: An episode requiring assistance of another person to actively administer carbohydrate, glucagon or take other corrective actions. plasma glucose (PG) concentrations may not be available during an event, but neurological recovery following the return of PG to normal is considered sufficient evidence that the event was induced by a low PG concentration. Blood glucose (BG) confirmed symptomatic hypoglycaemia: An episode that is BG confirmed by PG value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.
Time Frame	Week 0 to week 75

Outcome Measure Data

Analysis Population Description

SAS included all randomised participants exposed to at least one dose of randomised treatment. 'Overall Number of Participants Analysed' = participants with available data.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Measure Participants	403	402
Number [Episodes]	51	18

38. Secondary Outcome

Title	Change in Pulse - Semaglutide 2.4 mg Versus Placebo
Description	Change in pulse from baseline (week 0) to week 68 is presented. Results are based on the data from on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 2 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses.
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

SAS included all randomised participants exposed to at least one dose of randomised treatment. 'Overall Number of Participants Analysed' = participants with available data.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Measure Participants	351	340
Mean (Standard Deviation) [Beats/minute]	2 (9)	0 (9)

39. Secondary Outcome

Title	Change in Amylase - Semaglutide 2.4 mg Versus Placebo
Description	Change in amylase (units/litre) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 2 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses.
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

SAS included all randomised participants exposed to at least one dose of randomised treatment. 'Overall Number of Participants Analysed' = participants with available data.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Measure Participants	350	338
Geometric Mean (Geometric Coefficient of Variation) [Ratio of amylase]	1.24 (28.3)	1.06 (25.0)

40. Secondary Outcome

Title	Change in Lipase - Semaglutide 2.4 mg Versus Placebo
Description	Change in lipase (units/litre) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 2 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses.
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

SAS included all randomised participants exposed to at least one dose of randomised treatment. 'Overall Number of Participants Analysed' = participants with available data.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Measure Participants	350	338
Geometric Mean (Geometric Coefficient of Variation) [Ratio of lipase]	1.41 (57.2)	0.99 (51.8)

41. Secondary Outcome

Title	Change in Calcitonin - Semaglutide 2.4 mg Versus Placebo
Description	Change in calcitonin (nanogram/litre) from baseline (week 0) to week 68 is presented as ratio to baseline. Results are based on the data from on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 2 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses.
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

SAS included all randomised participants exposed to at least one dose of randomised treatment. 'Overall Number of Participants Analysed' = participants with available data.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Measure Participants	348	339
Geometric Mean (Geometric Coefficient of Variation) [Ratio of calcitonin]	0.94 (60.3)	0.96 (38.6)

Adverse Events

Time Frame	Week 0 to week 75. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.
Adverse Event Reporting Description	All presented AEs are treatment-emergent (i.e., TEAEs).
Arm/Group Title	Semaglutide 1.0 mg		Semaglutide 2.4 mg		Placebo
Arm/Group Description	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.		Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.		Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
All Cause Mortality
	Semaglutide 1.0 mg		Semaglutide 2.4 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/402 (0.2%)		1/403 (0.2%)		1/402 (0.2%)
Serious Adverse Events
	Semaglutide 1.0 mg		Semaglutide 2.4 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/402 (7.7%)		40/403 (9.9%)		37/402 (9.2%)
Cardiac disorders
Acute myocardial infarction	2/402 (0.5%)	2	1/403 (0.2%)	1	1/402 (0.2%)	1
Angina pectoris	1/402 (0.2%)	1	0/403 (0%)	0	1/402 (0.2%)	1
Angina unstable	0/402 (0%)	0	1/403 (0.2%)	1	0/402 (0%)	0
Atrial fibrillation	2/402 (0.5%)	2	2/403 (0.5%)	2	2/402 (0.5%)	2
Bradycardia	1/402 (0.2%)	1	0/403 (0%)	0	0/402 (0%)	0
Cardiac failure acute	0/402 (0%)	0	0/403 (0%)	0	1/402 (0.2%)	1
Cardiac failure congestive	1/402 (0.2%)	1	1/403 (0.2%)	1	1/402 (0.2%)	1
Myocardial infarction	1/402 (0.2%)	1	1/403 (0.2%)	1	0/402 (0%)	0
Myocardial ischaemia	1/402 (0.2%)	1	0/403 (0%)	0	0/402 (0%)	0
Supraventricular tachycardia	0/402 (0%)	0	1/403 (0.2%)	1	0/402 (0%)	0
Eye disorders
Cataract	0/402 (0%)	0	0/403 (0%)	0	1/402 (0.2%)	1
Glaucoma	0/402 (0%)	0	1/403 (0.2%)	1	0/402 (0%)	0
Gastrointestinal disorders
Abdominal pain	3/402 (0.7%)	3	0/403 (0%)	0	0/402 (0%)	0
Diarrhoea	1/402 (0.2%)	1	0/403 (0%)	0	0/402 (0%)	0
Diverticular perforation	0/402 (0%)	0	0/403 (0%)	0	1/402 (0.2%)	1
Food poisoning	0/402 (0%)	0	1/403 (0.2%)	1	0/402 (0%)	0
Gastric ulcer	1/402 (0.2%)	1	0/403 (0%)	0	0/402 (0%)	0
Gastritis	0/402 (0%)	0	1/403 (0.2%)	1	0/402 (0%)	0
Inguinal hernia	0/402 (0%)	0	0/403 (0%)	0	1/402 (0.2%)	1
Nausea	2/402 (0.5%)	2	1/403 (0.2%)	1	0/402 (0%)	0
Obstructive pancreatitis	0/402 (0%)	0	0/403 (0%)	0	1/402 (0.2%)	1
Small intestinal obstruction	0/402 (0%)	0	1/403 (0.2%)	1	0/402 (0%)	0
Upper gastrointestinal haemorrhage	0/402 (0%)	0	1/403 (0.2%)	1	0/402 (0%)	0
Vomiting	0/402 (0%)	0	2/403 (0.5%)	2	0/402 (0%)	0
General disorders
Chest pain	0/402 (0%)	0	0/403 (0%)	0	1/402 (0.2%)	1
Hepatobiliary disorders
Cholecystitis acute	0/402 (0%)	0	0/403 (0%)	0	1/402 (0.2%)	1
Cholecystitis chronic	0/402 (0%)	0	1/403 (0.2%)	1	0/402 (0%)	0
Cholelithiasis	1/402 (0.2%)	1	1/403 (0.2%)	1	0/402 (0%)	0
Non-alcoholic steatohepatitis	0/402 (0%)	0	1/403 (0.2%)	1	0/402 (0%)	0
Immune system disorders
Immunisation reaction	1/402 (0.2%)	1	0/403 (0%)	0	0/402 (0%)	0
Infections and infestations
Appendicitis	0/402 (0%)	0	1/403 (0.2%)	1	1/402 (0.2%)	1
Bronchitis	0/402 (0%)	0	0/403 (0%)	0	1/402 (0.2%)	1
Cellulitis	2/402 (0.5%)	2	0/403 (0%)	0	1/402 (0.2%)	1
Colonic abscess	0/402 (0%)	0	0/403 (0%)	0	1/402 (0.2%)	1
Cystitis	0/402 (0%)	0	1/403 (0.2%)	1	0/402 (0%)	0
Diverticulitis	1/402 (0.2%)	1	0/403 (0%)	0	1/402 (0.2%)	1
Empyema	0/402 (0%)	0	0/403 (0%)	0	1/402 (0.2%)	1
Gastroenteritis	3/402 (0.7%)	3	3/403 (0.7%)	3	1/402 (0.2%)	1
Herpes zoster	0/402 (0%)	0	1/403 (0.2%)	1	0/402 (0%)	0
Joint abscess	0/402 (0%)	0	0/403 (0%)	0	1/402 (0.2%)	1
Kidney infection	0/402 (0%)	0	0/403 (0%)	0	1/402 (0.2%)	1
Osteomyelitis	0/402 (0%)	0	0/403 (0%)	0	1/402 (0.2%)	1
Pharyngitis streptococcal	0/402 (0%)	0	0/403 (0%)	0	1/402 (0.2%)	1
Pneumonia	1/402 (0.2%)	1	1/403 (0.2%)	1	2/402 (0.5%)	2
Pneumonia influenzal	0/402 (0%)	0	1/403 (0.2%)	1	0/402 (0%)	0
Postoperative wound infection	1/402 (0.2%)	1	0/403 (0%)	0	0/402 (0%)	0
Respiratory tract infection	0/402 (0%)	0	1/403 (0.2%)	1	0/402 (0%)	0
Sepsis	3/402 (0.7%)	3	0/403 (0%)	0	0/402 (0%)	0
Urosepsis	0/402 (0%)	0	1/403 (0.2%)	1	0/402 (0%)	0
Viral infection	0/402 (0%)	0	1/403 (0.2%)	1	0/402 (0%)	0
Wound infection staphylococcal	0/402 (0%)	0	0/403 (0%)	0	1/402 (0.2%)	1
Injury, poisoning and procedural complications
Anaemia postoperative	0/402 (0%)	0	0/403 (0%)	0	1/402 (0.2%)	1
Ankle fracture	1/402 (0.2%)	1	0/403 (0%)	0	0/402 (0%)	0
Cervical vertebral fracture	0/402 (0%)	0	1/403 (0.2%)	1	0/402 (0%)	0
Fall	0/402 (0%)	0	1/403 (0.2%)	1	0/402 (0%)	0
Hip fracture	1/402 (0.2%)	1	0/403 (0%)	0	0/402 (0%)	0
Humerus fracture	0/402 (0%)	0	1/403 (0.2%)	1	0/402 (0%)	0
Joint dislocation	0/402 (0%)	0	0/403 (0%)	0	1/402 (0.2%)	1
Ligament rupture	1/402 (0.2%)	1	0/403 (0%)	0	0/402 (0%)	0
Lisfranc fracture	0/402 (0%)	0	0/403 (0%)	0	1/402 (0.2%)	1
Post procedural haemorrhage	0/402 (0%)	0	1/403 (0.2%)	1	0/402 (0%)	0
Rib fracture	0/402 (0%)	0	2/403 (0.5%)	2	0/402 (0%)	0
Road traffic accident	0/402 (0%)	0	1/403 (0.2%)	1	0/402 (0%)	0
Skin laceration	0/402 (0%)	0	1/403 (0.2%)	1	0/402 (0%)	0
Spinal compression fracture	0/402 (0%)	0	1/403 (0.2%)	1	0/402 (0%)	0
Subdural haematoma	0/402 (0%)	0	0/403 (0%)	0	1/402 (0.2%)	1
Thoracic vertebral fracture	0/402 (0%)	0	1/403 (0.2%)	1	0/402 (0%)	0
Traumatic haemothorax	0/402 (0%)	0	1/403 (0.2%)	1	0/402 (0%)	0
Upper limb fracture	0/402 (0%)	0	1/403 (0.2%)	1	0/402 (0%)	0
Metabolism and nutrition disorders
Cachexia	1/402 (0.2%)	1	0/403 (0%)	0	0/402 (0%)	0
Decreased appetite	1/402 (0.2%)	1	0/403 (0%)	0	0/402 (0%)	0
Dehydration	2/402 (0.5%)	2	1/403 (0.2%)	1	1/402 (0.2%)	1
Diabetes mellitus inadequate control	0/402 (0%)	0	0/403 (0%)	0	1/402 (0.2%)	1
Diabetic ketoacidosis	0/402 (0%)	0	1/403 (0.2%)	1	0/402 (0%)	0
Diabetic metabolic decompensation	0/402 (0%)	0	0/403 (0%)	0	1/402 (0.2%)	1
Hyperglycaemia	1/402 (0.2%)	1	0/403 (0%)	0	0/402 (0%)	0
Hyponatraemia	0/402 (0%)	0	1/403 (0.2%)	1	0/402 (0%)	0
Ketoacidosis	0/402 (0%)	0	1/403 (0.2%)	1	0/402 (0%)	0
Lactic acidosis	1/402 (0.2%)	1	0/403 (0%)	0	0/402 (0%)	0
Obesity	0/402 (0%)	0	0/403 (0%)	0	1/402 (0.2%)	1
Musculoskeletal and connective tissue disorders
Neuropathic arthropathy	0/402 (0%)	0	0/403 (0%)	0	1/402 (0.2%)	1
Osteoarthritis	0/402 (0%)	0	1/403 (0.2%)	1	0/402 (0%)	0
Pain in extremity	0/402 (0%)	0	0/403 (0%)	0	1/402 (0.2%)	1
Rotator cuff syndrome	1/402 (0.2%)	1	0/403 (0%)	0	0/402 (0%)	0
Spondylolisthesis	1/402 (0.2%)	1	0/403 (0%)	0	0/402 (0%)	0
Trigger finger	0/402 (0%)	0	1/403 (0.2%)	1	0/402 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma gastric	1/402 (0.2%)	1	0/403 (0%)	0	0/402 (0%)	0
Adenocarcinoma of colon	1/402 (0.2%)	1	0/403 (0%)	0	0/402 (0%)	0
Gastric cancer	0/402 (0%)	0	0/403 (0%)	0	1/402 (0.2%)	1
Gastric cancer stage IV	0/402 (0%)	0	0/403 (0%)	0	1/402 (0.2%)	1
Gastrointestinal lymphoma	0/402 (0%)	0	1/403 (0.2%)	1	0/402 (0%)	0
Gastrointestinal stromal tumour	1/402 (0.2%)	1	0/403 (0%)	0	0/402 (0%)	0
Hepatocellular carcinoma	0/402 (0%)	0	0/403 (0%)	0	1/402 (0.2%)	1
Invasive ductal breast carcinoma	1/402 (0.2%)	1	0/403 (0%)	0	0/402 (0%)	0
Keratinising squamous cell carcinoma of nasopharynx	0/402 (0%)	0	0/403 (0%)	0	1/402 (0.2%)	1
Myeloid leukaemia	0/402 (0%)	0	1/403 (0.2%)	1	0/402 (0%)	0
Neuroendocrine tumour	1/402 (0.2%)	1	0/403 (0%)	0	0/402 (0%)	0
Prostate cancer	0/402 (0%)	0	0/403 (0%)	0	2/402 (0.5%)	2
Uterine cancer	1/402 (0.2%)	1	0/403 (0%)	0	0/402 (0%)	0
Nervous system disorders
Cerebral artery thrombosis	0/402 (0%)	0	1/403 (0.2%)	1	0/402 (0%)	0
Cerebral infarction	0/402 (0%)	0	1/403 (0.2%)	1	0/402 (0%)	0
Cerebrovascular accident	0/402 (0%)	0	1/403 (0.2%)	1	1/402 (0.2%)	1
Hepatic encephalopathy	0/402 (0%)	0	1/403 (0.2%)	1	0/402 (0%)	0
Hyperaesthesia	0/402 (0%)	0	1/403 (0.2%)	1	0/402 (0%)	0
Hyponatraemic encephalopathy	0/402 (0%)	0	1/403 (0.2%)	1	0/402 (0%)	0
Ischaemic stroke	1/402 (0.2%)	1	0/403 (0%)	0	1/402 (0.2%)	1
Presyncope	0/402 (0%)	0	0/403 (0%)	0	1/402 (0.2%)	1
Spinal epidural haematoma	0/402 (0%)	0	1/403 (0.2%)	1	0/402 (0%)	0
Subarachnoid haemorrhage	0/402 (0%)	0	1/403 (0.2%)	1	0/402 (0%)	0
Syncope	1/402 (0.2%)	1	1/403 (0.2%)	1	0/402 (0%)	0
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	0/402 (0%)	0	0/403 (0%)	0	1/402 (0.2%)	1
Renal and urinary disorders
Acute kidney injury	2/402 (0.5%)	2	2/403 (0.5%)	3	1/402 (0.2%)	1
Bladder outlet obstruction	0/402 (0%)	0	1/403 (0.2%)	1	0/402 (0%)	0
Stag horn calculus	0/402 (0%)	0	1/403 (0.2%)	1	0/402 (0%)	0
Ureterolithiasis	0/402 (0%)	0	0/403 (0%)	0	2/402 (0.5%)	2
Reproductive system and breast disorders
Uterine polyp	0/402 (0%)	0	1/403 (0.2%)	1	0/402 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/402 (0.2%)	1	1/403 (0.2%)	1	0/402 (0%)	0
Asthma	0/402 (0%)	0	1/403 (0.2%)	1	1/402 (0.2%)	1
Pneumothorax	0/402 (0%)	0	1/403 (0.2%)	1	0/402 (0%)	0
Surgical and medical procedures
Cardiac pacemaker replacement	1/402 (0.2%)	1	0/403 (0%)	0	0/402 (0%)	0
Sperm aspiration	0/402 (0%)	0	0/403 (0%)	0	1/402 (0.2%)	1
Stent placement	0/402 (0%)	0	0/403 (0%)	0	1/402 (0.2%)	1
Thyroidectomy	0/402 (0%)	0	1/403 (0.2%)	1	0/402 (0%)	0
Vascular disorders
Aortic rupture	0/402 (0%)	0	1/403 (0.2%)	1	0/402 (0%)	0
Hypertension	0/402 (0%)	0	2/403 (0.5%)	2	0/402 (0%)	0
Hypertensive urgency	0/402 (0%)	0	0/403 (0%)	0	1/402 (0.2%)	1
Shock	1/402 (0.2%)	1	0/403 (0%)	0	0/402 (0%)	0
Other (Not Including Serious) Adverse Events
	Semaglutide 1.0 mg		Semaglutide 2.4 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	261/402 (64.9%)		284/403 (70.5%)		190/402 (47.3%)
Gastrointestinal disorders
Abdominal distension	9/402 (2.2%)	12	24/403 (6%)	30	11/402 (2.7%)	13
Constipation	51/402 (12.7%)	70	70/403 (17.4%)	82	22/402 (5.5%)	26
Diarrhoea	88/402 (21.9%)	157	86/403 (21.3%)	141	48/402 (11.9%)	66
Dyspepsia	27/402 (6.7%)	27	25/403 (6.2%)	30	5/402 (1.2%)	5
Flatulence	21/402 (5.2%)	25	16/403 (4%)	21	7/402 (1.7%)	9
Nausea	128/402 (31.8%)	196	135/403 (33.5%)	248	37/402 (9.2%)	45
Vomiting	54/402 (13.4%)	93	86/403 (21.3%)	186	11/402 (2.7%)	12
General disorders
Fatigue	19/402 (4.7%)	26	28/403 (6.9%)	29	4/402 (1%)	4
Infections and infestations
Gastroenteritis	21/402 (5.2%)	25	11/403 (2.7%)	12	12/402 (3%)	14
Nasopharyngitis	47/402 (11.7%)	69	68/403 (16.9%)	115	59/402 (14.7%)	92
Upper respiratory tract infection	37/402 (9.2%)	54	42/403 (10.4%)	48	38/402 (9.5%)	50
Metabolism and nutrition disorders
Decreased appetite	29/402 (7.2%)	33	38/403 (9.4%)	41	15/402 (3.7%)	17
Musculoskeletal and connective tissue disorders
Arthralgia	24/402 (6%)	27	23/403 (5.7%)	29	20/402 (5%)	20
Back pain	28/402 (7%)	30	27/403 (6.7%)	30	14/402 (3.5%)	15
Nervous system disorders
Headache	33/402 (8.2%)	48	31/403 (7.7%)	40	20/402 (5%)	27

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

At the end of the trial, one or more scientific publications may be prepared collaboratively by the investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for up to 60 days to protect intellectual property.