STEP 3: Research Study to Look at How Well Semaglutide is at Lowering Weight When Taken Together With an Intensive Lifestyle Program

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03611582
• Collaborator: (none)
• Enrollment: 611
• Locations: 41
• Arms: 2
• Actual Duration (Months): 20.9
• Patients Per Site: 14.9
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

This study will look at the change in 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. Together with the medicine, the participant will also be part of an intensive lifestyle program where the participant will have talks with study staff about healthy food choices, what the participant can do to lose weight and be more physically active. The participant will either get semaglutide or "dummy" medicine - which treatment the participant gets is decided by chance. The participant will need to take 1 injection once a week. The study medicine is injected with a thin needle in a skin fold in the stomach, thigh or upper arm. For the first 2 months the participant will be on a low calorie diet. The diet is made up of bars, shakes and 1 low calorie pre-prepared meal for each day. The study will last for about 1.5 years. The participant will have 32 clinic visits with the study doctor.

Condition or Disease	Intervention/Treatment	Phase
Overweight; Obesity	Drug: Semaglutide; Drug: Placebo (semaglutide)	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 611 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 as Adjunct to Intensive Behavioural Therapy in Subjects With Overweight or Obesity
• Actual Study Start Date: Aug 1, 2018
• Actual Primary Completion Date: Mar 18, 2020
• Actual Study Completion Date: Apr 28, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Semaglutide Participants will receive semaglutide 2.4 mg during 68-week treatment period in addition to intensive behavioural therapy.	Drug: Semaglutide; Subcutaneous (s.c., under the skin) injections of semaglutide once weekly at escalating doses (0.25 mg/week, 0.5 mg/week, 1.0 mg/week, 1.7 mg/week, 2.4 mg/week). The dose will be escalated to next level every 4 weeks.
Placebo Comparator: Semaglutide placebo Participants will receive semaglutide placebo during 68-week treatment period in addition to intensive behavioural therapy.	Drug: Placebo (semaglutide); S.c. injections of placebo once weekly at a similar dose escalation manner as semaglutide (placebo matched to semaglutide 0.25 mg/week, 0.5 mg/week, 1.0 mg/week, 1.7 mg/week, 2.4 mg/week). The dose will be escalated to next level every 4 weeks.

Outcome Measures

Primary Outcome Measures

1. Change in Body Weight (%) [Baseline (week 0) to week 68]

   Change in body weight from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from both in-trial and on-treatment 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: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68), including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).

2. Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 5% [After 68 weeks]

   Number of participants who achieved greater than or equal to (≥) 5% weight loss after 68 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved ≥ 5% weight loss, whereas 'No' infers the number of participants who have not achieved ≥ 5% weight loss. The endpoint was evaluated based on the data from both in-trial and on-treatment observation periods. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75). On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68), including 2 weeks of follow-up. It excludes any period of temporary treatment interruption.

Secondary Outcome Measures

1. Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 10% [After 68 weeks]

   Number of participants who achieved greater than or equal to (≥) 10% weight loss after 68 weeks is presented. In the reported data, 'Yes' infers number of participants who have achieved ≥ 10% weight loss whereas 'No' infers number of participants who have not achieved ≥ 10% weight loss. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).

2. Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 15% [After 68 weeks]

   Number of participants who achieved greater than or equal to (≥) 15% weight loss after 68 weeks is presented. In the reported data, 'Yes' infers number of participants who have achieved ≥ 15% weight loss whereas 'No' infers number of participants who have not achieved ≥ 15% weight loss. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).

3. Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 20% [After 68 weeks]

   Number of participants who achieved greater than or equal to (≥) 20% weight loss after 68 weeks is presented. In the reported data, 'Yes' infers number of participants who have achieved ≥ 20% weight loss whereas 'No' infers number of participants who have not achieved ≥ 20% weight loss. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).

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

   Change in waist circumference from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).

5. 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. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).

6. Change in Short Form-36 (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 eight domains of functional health and well-being as well as two component summary scores (physical component summary and mental component summary). 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. These endpoints were evaluated based on the data from in-trial observation period which is the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).

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

   Change in body weight from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).

8. Change in Body Mass Index [Baseline (week 0) to week 68]

   Change in body mass index from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).

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

   Change in glycosylated haemoglobin (HbA1c) from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).

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

    Change in HbA1c from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).

11. Change in Fasting Plasma Glucose [Baseline (week 0) to week 68]

    Change in fasting plasma glucose from week 0 to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).

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

    Change in fasting serum insulin from week 0 to week 68 [measured as milli-international units per milliliter (mIU/mL)] is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).

13. 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. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).

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

    Change in fasting total cholesterol from baseline (week 0) to week 68 (measured as mg/dL) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).

15. Change in High-density Lipoproteins (HDL) [Baseline (week 0) to week 68]

    Change in fasting HDL from baseline (week 0) to week 68 (measured as mg/dL) is presented as ratio to baseline.The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).

16. Change in Low-density Lipoproteins (LDL) [Baseline (week 0) to week 68]

    Change in fasting LDL from baseline (week 0) to week 68 (measured as mg/dL) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).

17. Change in Very Low Density Lipoprotein (VLDL) [Baseline (week 0) to week 68]

    Change in fasting VLDL from baseline (week 0) to week 68 (measured as mg/dL) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).

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

    Change in fasting free fatty acids from baseline (week 0) to week 68 (measured as mg/dL) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).

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

    Change in fasting triglycerides from baseline (week 0) to week 68 (measured as mg/dL) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).

20. Change in High Sensitivity C-reactive Protein [Baseline (week 0) to week 68]

    Change in high sensitivity C-reactive protein from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).

21. Change in Plasminogen Activator Inhibitor-1 Activity [Baseline (week 0) to week 68]

    Change in plasminogen activator inhibitor-1 activity from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).

22. Participants Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score [After 68 weeks]

    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 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. The endpoint was evaluated based on the in-trial observation period which is uninterrupted time interval from randomization (week 0) to last trial related subject-site contact (week 75).

23. Change in Body Weight [Baseline (week 0) to week 8]

    Change in body weight from baseline (week 0) to week 8 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).

24. Number of Treatment-emergent Adverse Events (AEs) [Baseline (week 0) to week 75]

    An adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. All AEs mentioned here are treatment emergent adverse events (TEAE) defined as an event that had onset date (or increase in severity) on or after the first day of exposure to treatment. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68), including 7 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 7 consecutive missed doses (off-treatment period).

25. Number of Serious Adverse Events (SAEs) [Baseline (week 0) to week 75]

    A serious adverse event (SAE) is defined as any untoward medical occurrence that at any dose results in death, or is life-threatening, or requires inpatient hospitalization or causes prolongation of existing hospitalization results in persistent or significant disability/incapacity, or may have caused a congenital anomaly/birth defect, or requires intervention to prevent permanent impairment or damage. The SAEs occurred from week 0 to week 75 is presented. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68), including 7 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 7 consecutive missed doses (off-treatment period).

26. Change in Pulse [Baseline (week 0) to week 68]

    Change in pulse from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).

27. Change in Amylase [Baseline (week 0) to week 68]

    Change in amylase (measured as U/L) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).

28. Change in Lipase [Baseline (week 0) to week 68]

    Change in lipase (measured as U/L) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).

29. Change in Calcitonin [Baseline (week 0) to week 68]

    Change in calcitonin (measured as ng/L) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).

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 more than or equal to 18 years at the time of signing informed consent

• Body mass index more than or equal to 30 kg/m^{2 or more than or equal to 27 kg/m}2 with the presence of at least one of the following weight-related comorbidities (treated or untreated): hypertension, dyslipidaemia, obstructive sleep apnoea or cardiovascular disease

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

Exclusion Criteria:

• Hemoglobin A1c more than or equal to 48 mmol/mol (6.5%) as measured by the central laboratory at screening

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Birmingham	Alabama	United States	35294
2	Novo Nordisk Investigational Site	Montgomery	Alabama	United States	36106
3	Novo Nordisk Investigational Site	Peoria	Arizona	United States	85381
4	Novo Nordisk Investigational Site	Anaheim	California	United States	92801
5	Novo Nordisk Investigational Site	Escondido	California	United States	92025
6	Novo Nordisk Investigational Site	Fresno	California	United States	93720
7	Novo Nordisk Investigational Site	Fullerton	California	United States	92835
8	Novo Nordisk Investigational Site	Huntington Beach	California	United States	92648
9	Novo Nordisk Investigational Site	Los Angeles	California	United States	90057
10	Novo Nordisk Investigational Site	Walnut Creek	California	United States	94598
11	Novo Nordisk Investigational Site	Golden	Colorado	United States	80401
12	Novo Nordisk Investigational Site	Kissimmee	Florida	United States	34744
13	Novo Nordisk Investigational Site	Panama City	Florida	United States	32401
14	Novo Nordisk Investigational Site	Plantation	Florida	United States	33324
15	Novo Nordisk Investigational Site	Roswell	Georgia	United States	30076
16	Novo Nordisk Investigational Site	Honolulu	Hawaii	United States	96814
17	Novo Nordisk Investigational Site	Chicago	Illinois	United States	60607
18	Novo Nordisk Investigational Site	Evanston	Illinois	United States	60201-2477
19	Novo Nordisk Investigational Site	Skokie	Illinois	United States	60077
20	Novo Nordisk Investigational Site	Albany	New York	United States	12203
21	Novo Nordisk Investigational Site	Endwell	New York	United States	13760
22	Novo Nordisk Investigational Site	Chapel Hill	North Carolina	United States	27517
23	Novo Nordisk Investigational Site	Greensboro	North Carolina	United States	27408
24	Novo Nordisk Investigational Site	Hickory	North Carolina	United States	28601
25	Novo Nordisk Investigational Site	Raleigh	North Carolina	United States	27609
26	Novo Nordisk Investigational Site	Wilmington	North Carolina	United States	28401
27	Novo Nordisk Investigational Site	Philadelphia	Pennsylvania	United States	19104-3317
28	Novo Nordisk Investigational Site	Charleston	South Carolina	United States	29425
29	Novo Nordisk Investigational Site	Mount Pleasant	South Carolina	United States	29464
30	Novo Nordisk Investigational Site	Knoxville	Tennessee	United States	37912
31	Novo Nordisk Investigational Site	Austin	Texas	United States	78731
32	Novo Nordisk Investigational Site	Dallas	Texas	United States	75226
33	Novo Nordisk Investigational Site	Dallas	Texas	United States	75230
34	Novo Nordisk Investigational Site	Dallas	Texas	United States	75231
35	Novo Nordisk Investigational Site	Rockwall	Texas	United States	75032
36	Novo Nordisk Investigational Site	Round Rock	Texas	United States	78681
37	Novo Nordisk Investigational Site	Saint George	Utah	United States	84790
38	Novo Nordisk Investigational Site	Arlington	Virginia	United States	22206
39	Novo Nordisk Investigational Site	Newport News	Virginia	United States	23606
40	Novo Nordisk Investigational Site	Winchester	Virginia	United States	22601-3834
41	Novo Nordisk Investigational Site	Olympia	Washington	United States	98502

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 - Aug 3, 2020
• Statistical Analysis Plan - Jul 28, 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: NCT03611582
• Other Study ID Numbers: NN9536-4375; U1111-1200-8199
• First Posted: Aug 2, 2018
• Last Update Posted: Nov 11, 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 in 41 sites in the United States.
Pre-assignment Detail	The trial has a 68-week treatment period (16 weeks of dose escalation and 52 weeks of maintenance dose). Participants were randomised in 2:1 ratio either to receive semaglutide 2.4 mg or placebo.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.	Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Period Title: Overall Study
STARTED	407	204
Full Analysis Set (FAS)	407	204
Safety Analysis Set (SAS)	407	204
COMPLETED	339	166
NOT COMPLETED	68	38

Baseline Characteristics

Arm/Group Title	Semaglutide 2.4 mg	Placebo	Total
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.	Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.	Total of all reporting groups
Overall Participants	407	204	611
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	46 (13)	46 (13)	46 (13)
Sex: Female, Male (Count of Participants)
Female	315 77.4%	180 88.2%	495 81%
Male	92 22.6%	24 11.8%	116 19%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	75 18.4%	46 22.5%	121 19.8%
Not Hispanic or Latino	332 81.6%	158 77.5%	490 80.2%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.2%	0 0%	1 0.2%
Asian	5 1.2%	6 2.9%	11 1.8%
Native Hawaiian or Other Pacific Islander	3 0.7%	0 0%	3 0.5%
Black or African American	80 19.7%	36 17.6%	116 19%
White	307 75.4%	158 77.5%	465 76.1%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	11 2.7%	4 2%	15 2.5%

Outcome Measures

1. Primary Outcome

Title	Change in Body Weight (%)
Description	Change in body weight from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from both in-trial and on-treatment 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: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68), including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = full analysis set (FAS) which comprised all randomized participants. Number Analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.	Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Measure Participants	407	204
In-trial observation period	-16.5 (10.1)	-5.8 (7.7)
On-treatment observation period	-17.6 (9.6)	-6.1 (7.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Semaglutide 2.4 mg, Placebo
	Comments	Treatment policy estimand
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-10.27
	Confidence Interval	(2-Sided) 95%; -11.97 to -8.57
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Semaglutide 2.4 mg, Placebo
	Comments	Hypothetical estimand
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	MMRM (mixed model repeated measurement)
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-12.67
	Confidence Interval	(2-Sided) 95%; -14.34 to -11.00
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 5%
Description	Number of participants who achieved greater than or equal to (≥) 5% weight loss after 68 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved ≥ 5% weight loss, whereas 'No' infers the number of participants who have not achieved ≥ 5% weight loss. The endpoint was evaluated based on the data from both in-trial and on-treatment observation periods. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75). On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68), including 2 weeks of follow-up. It excludes any period of temporary treatment interruption.
Time Frame	After 68 weeks

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = full analysis set (FAS) which comprised all randomized participants. Number Analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.	Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Measure Participants	407	204
Yes	323 79.4%	90 44.1%
No	50 12.3%	99 48.5%
Yes	300 73.7%	82 40.2%
No	34 8.4%	82 40.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Semaglutide 2.4 mg, Placebo
	Comments	Treatment policy estimand
	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	6.11
	Confidence Interval	(2-Sided) 95%; 4.04 to 9.26
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Semaglutide 2.4 mg, Placebo
	Comments	Hypothetical estimand
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	MMRM (mixed model repeated measurement)
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	11.67
	Confidence Interval	(2-Sided) 95%; 7.64 to 17.81
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 10%
Description	Number of participants who achieved greater than or equal to (≥) 10% weight loss after 68 weeks is presented. In the reported data, 'Yes' infers number of participants who have achieved ≥ 10% weight loss whereas 'No' infers number of participants who have not achieved ≥ 10% weight loss. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
Time Frame	After 68 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.	Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Measure Participants	373	189
Yes	281 69%	51 25%
No	92 22.6%	138 67.6%

4. Secondary Outcome

Title	Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 15%
Description	Number of participants who achieved greater than or equal to (≥) 15% weight loss after 68 weeks is presented. In the reported data, 'Yes' infers number of participants who have achieved ≥ 15% weight loss whereas 'No' infers number of participants who have not achieved ≥ 15% weight loss. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
Time Frame	After 68 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.	Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Measure Participants	373	189
Yes	208 51.1%	25 12.3%
No	165 40.5%	164 80.4%

5. Secondary Outcome

Title	Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 20%
Description	Number of participants who achieved greater than or equal to (≥) 20% weight loss after 68 weeks is presented. In the reported data, 'Yes' infers number of participants who have achieved ≥ 20% weight loss whereas 'No' infers number of participants who have not achieved ≥ 20% weight loss. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
Time Frame	After 68 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.	Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Measure Participants	373	189
Yes	133 32.7%	7 3.4%
No	240 59%	182 89.2%

6. Secondary Outcome

Title	Change in Waist Circumference
Description	Change in waist circumference from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.	Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Measure Participants	371	189
Mean (Standard Deviation) [Centimeter (cm)]	-15.2 (10.2)	-6.1 (8.6)

7. Secondary Outcome

Title	Change in Systolic Blood Pressure
Description	Change in systolic blood pressure from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.	Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Measure Participants	372	188
Mean (Standard Deviation) [Millimeters of mercury (mmHg)]	-6 (14)	-2 (15)

8. Secondary Outcome

Title	Change in Short Form-36 (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 eight domains of functional health and well-being as well as two component summary scores (physical component summary and mental component summary). 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. These endpoints were evaluated based on the data from in-trial observation period which is the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = full analysis set (FAS) which comprised all randomized participants. Number Analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.	Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Measure Participants	407	204
Change in physical functioning score (SF-36)	2.5 (5.7)	1.7 (5.7)
Change in SF-36: Role-Physical score	1.6 (6.5)	1.5 (6.7)
Change in SF-36: Bodily Pain score	1.3 (7.1)	0.6 (8.3)
Change in SF-36: General Health score	3.4 (6.6)	1.9 (6.4)
Change in SF-36: Vitality score	2.0 (8.2)	0.9 (7.8)
Change in SF-36: Social Functioning score	0.1 (6.6)	-1.2 (8.0)
Change in SF-36: Mental Health score	-0.5 (6.0)	-1.5 (7.1)
Change in SF-36: Physical component summary	3.2 (6.0)	2.6 (6.5)
Change in SF-36: Mental component summary	-0.9 (6.0)	-2.2 (8.0)
Change in SF-36: Role-Emotional score	-0.6 (5.6)	-1.5 (7.7)

9. Secondary Outcome

Title	Change in Body Weight (Kg)
Description	Change in body weight from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.	Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Measure Participants	373	189
Mean (Standard Deviation) [Kilogram (kg)]	-17.5 (11.4)	-6.2 (8.6)

10. Secondary Outcome

Title	Change in Body Mass Index
Description	Change in body mass index from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = full analysis set (FAS) which comprised all randomized participants. Number Analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.	Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Measure Participants	373	189
Mean (Standard Deviation) [Kilogram per square meter (kg/sqm)]	-6.2 (4.0)	-2.2 (3.1)

11. Secondary Outcome

Title	Change in HbA1c (%)
Description	Change in glycosylated haemoglobin (HbA1c) from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.	Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Measure Participants	369	184
Mean (Standard Deviation) [Percentage point of HbA1c]	-0.5 (0.3)	-0.3 (0.2)

12. Secondary Outcome

Title	Change in HbA1c (mmol/Mol)
Description	Change in HbA1c from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.	Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Measure Participants	369	184
Mean (Standard Deviation) [mmol/mol]	-5.8 (3.1)	-3.1 (2.5)

13. Secondary Outcome

Title	Change in Fasting Plasma Glucose
Description	Change in fasting plasma glucose from week 0 to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.	Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Measure Participants	355	176
Mean (Standard Deviation) [milligrams per deciliter (mg/dL)]	-7.3 (10.9)	-1.1 (10.6)

14. Secondary Outcome

Title	Change in Fasting Serum Insulin
Description	Change in fasting serum insulin from week 0 to week 68 [measured as milli-international units per milliliter (mIU/mL)] is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.	Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Measure Participants	346	170
Geometric Mean (Geometric Coefficient of Variation) [Ratio of fasting serum insulin]	0.68 (67.4)	0.84 (50.6)

15. Secondary Outcome

Title	Change in Diastolic Blood Pressure
Description	Change in diastolic blood pressure from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.	Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Measure Participants	372	188
Mean (Standard Deviation) [mmHg]	-3 (10)	-1 (10)

16. Secondary Outcome

Title	Change in Total Cholesterol
Description	Change in fasting total cholesterol from baseline (week 0) to week 68 (measured as mg/dL) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.	Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Measure Participants	363	181
Geometric Mean (Geometric Coefficient of Variation) [Ratio of fasting total cholesterol]	0.96 (15.0)	1.01 (12.3)

17. Secondary Outcome

Title	Change in High-density Lipoproteins (HDL)
Description	Change in fasting HDL from baseline (week 0) to week 68 (measured as mg/dL) is presented as ratio to baseline.The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.	Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Measure Participants	363	181
Geometric Mean (Geometric Coefficient of Variation) [Ratio of fasting HDL cholesterol]	1.06 (14.6)	1.05 (15.0)

18. Secondary Outcome

Title	Change in Low-density Lipoproteins (LDL)
Description	Change in fasting LDL from baseline (week 0) to week 68 (measured as mg/dL) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.	Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Measure Participants	363	181
Geometric Mean (Geometric Coefficient of Variation) [Ratio of fasting LDL cholesterol]	0.96 (23.2)	1.01 (18.6)

19. Secondary Outcome

Title	Change in Very Low Density Lipoprotein (VLDL)
Description	Change in fasting VLDL from baseline (week 0) to week 68 (measured as mg/dL) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.	Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Measure Participants	363	181
Geometric Mean (Geometric Coefficient of Variation) [Ratio of fasting VLDL cholesterol]	0.77 (40.9)	0.91 (38.6)

20. Secondary Outcome

Title	Change in Free Fatty Acids
Description	Change in fasting free fatty acids from baseline (week 0) to week 68 (measured as mg/dL) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.	Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Measure Participants	346	171
Geometric Mean (Geometric Coefficient of Variation) [Ratio of fasting free fatty acids]	0.86 (69.9)	1.08 (71.8)

21. Secondary Outcome

Title	Change in Triglycerides
Description	Change in fasting triglycerides from baseline (week 0) to week 68 (measured as mg/dL) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.	Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Measure Participants	363	181
Geometric Mean (Geometric Coefficient of Variation) [Ratio of fasting triglycerides]	0.77 (41.3)	0.91 (39.1)

22. Secondary Outcome

Title	Change in High Sensitivity C-reactive Protein
Description	Change in high sensitivity C-reactive protein from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.	Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Measure Participants	363	182
Geometric Mean (Geometric Coefficient of Variation) [milligrams per litre (mg/L)]	0.40 (108.7)	0.76 (75.5)

23. Secondary Outcome

Title	Change in Plasminogen Activator Inhibitor-1 Activity
Description	Change in plasminogen activator inhibitor-1 activity from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.	Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Measure Participants	343	162
Geometric Mean (Geometric Coefficient of Variation) [Arbritary units per milliliter (AU/ml)]	0.92 (80.6)	1.26 (74.2)

24. 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 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. The endpoint was evaluated based on the in-trial observation period which is uninterrupted time interval from randomization (week 0) to last trial related subject-site contact (week 75).
Time Frame	After 68 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.	Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Measure Participants	364	181
Yes (with threshold 4.3)	86 21.1%	36 17.6%
No (with threshold 4.3)	278 68.3%	145 71.1%
Yes (with threshold 3.7)	133 32.7%	51 25%
No (with threshold 3.7)	231 56.8%	130 63.7%

25. Secondary Outcome

Title	Change in Body Weight
Description	Change in body weight from baseline (week 0) to week 8 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Baseline (week 0) to week 8

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.	Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Measure Participants	396	197
Mean (Standard Deviation) [Percentage]	-7.8 (3.1)	-6.0 (3.6)

26. Secondary Outcome

Title	Number of Treatment-emergent Adverse Events (AEs)
Description	An adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. All AEs mentioned here are treatment emergent adverse events (TEAE) defined as an event that had onset date (or increase in severity) on or after the first day of exposure to treatment. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68), including 7 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 7 consecutive missed doses (off-treatment period).
Time Frame	Baseline (week 0) to week 75

Outcome Measure Data

Analysis Population Description

SAS included all participants who received at least one dose of trial product.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.	Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Measure Participants	407	204
Number [events]	4035	1325

27. Secondary Outcome

Title	Number of Serious Adverse Events (SAEs)
Description	A serious adverse event (SAE) is defined as any untoward medical occurrence that at any dose results in death, or is life-threatening, or requires inpatient hospitalization or causes prolongation of existing hospitalization results in persistent or significant disability/incapacity, or may have caused a congenital anomaly/birth defect, or requires intervention to prevent permanent impairment or damage. The SAEs occurred from week 0 to week 75 is presented. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68), including 7 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 7 consecutive missed doses (off-treatment period).
Time Frame	Baseline (week 0) to week 75

Outcome Measure Data

Analysis Population Description

SAS included all participants who received at least one dose of trial product.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.	Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Measure Participants	407	204
Number [events]	55	7

28. Secondary Outcome

Title	Change in Pulse
Description	Change in pulse from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

SAS included all participants who received at least one dose of trial product. Overall number of participants analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.	Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Measure Participants	334	163
Mean (Standard Deviation) [beats per minute (bpm)]	3 (11)	2 (10)

29. Secondary Outcome

Title	Change in Amylase
Description	Change in amylase (measured as U/L) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

SAS included all participants who received at least one dose of trial product. Overall number of participants analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.	Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Measure Participants	332	161
Geometric Mean (Geometric Coefficient of Variation) [Ratio of amylase]	1.12 (19)	1.07 (18.1)

30. Secondary Outcome

Title	Change in Lipase
Description	Change in lipase (measured as U/L) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

SAS included all participants who received at least one dose of trial product. Overall number of participants analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.	Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Measure Participants	332	161
Geometric Mean (Geometric Coefficient of Variation) [Ratio of lipase]	1.31 (52)	0.94 (39.4)

31. Secondary Outcome

Title	Change in Calcitonin
Description	Change in calcitonin (measured as ng/L) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment observation period. On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68) including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

SAS included all participants who received at least one dose of trial product. Overall number of participants analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.	Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Measure Participants	332	162
Geometric Mean (Geometric Coefficient of Variation) [Ratio of calcitonin]	0.93 (40.6)	0.94 (33.2)

Adverse Events

Time Frame	week 0 to week 75 Results are based on the SAS which included all participants who received at least one dose of semaglutide or placebo.
Adverse Event Reporting Description	All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomised treatment and no later than the date of last dose + 7 weeks.
Arm/Group Title	Semaglutide 2.4 mg		Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.		Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
All Cause Mortality
	Semaglutide 2.4 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/407 (0%)		0/204 (0%)
Serious Adverse Events
	Semaglutide 2.4 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	37/407 (9.1%)		6/204 (2.9%)
Blood and lymphatic system disorders
Iron deficiency anaemia	1/407 (0.2%)	1	0/204 (0%)	0
Ear and labyrinth disorders
Vertigo	1/407 (0.2%)	1	0/204 (0%)	0
Gastrointestinal disorders
Abdominal pain	1/407 (0.2%)	1	0/204 (0%)	0
Haemorrhoids thrombosed	1/407 (0.2%)	1	0/204 (0%)	0
Incarcerated inguinal hernia	0/407 (0%)	0	1/204 (0.5%)	1
Inguinal hernia	0/407 (0%)	0	1/204 (0.5%)	1
Small intestinal obstruction	0/407 (0%)	0	1/204 (0.5%)	1
General disorders
Non-cardiac chest pain	1/407 (0.2%)	1	0/204 (0%)	0
Hepatobiliary disorders
Biliary dyskinesia	1/407 (0.2%)	1	0/204 (0%)	0
Cholecystitis	2/407 (0.5%)	2	0/204 (0%)	0
Cholecystitis acute	3/407 (0.7%)	3	0/204 (0%)	0
Cholelithiasis	7/407 (1.7%)	7	0/204 (0%)	0
Infections and infestations
Abdominal abscess	1/407 (0.2%)	1	0/204 (0%)	0
Appendicitis	3/407 (0.7%)	4	0/204 (0%)	0
Cellulitis	1/407 (0.2%)	1	0/204 (0%)	0
Gastroenteritis viral	1/407 (0.2%)	1	0/204 (0%)	0
Large intestine infection	1/407 (0.2%)	1	0/204 (0%)	0
Pelvic inflammatory disease	1/407 (0.2%)	1	0/204 (0%)	0
Pneumonia	1/407 (0.2%)	1	0/204 (0%)	0
Sepsis	1/407 (0.2%)	1	0/204 (0%)	0
Urinary tract infection	1/407 (0.2%)	1	0/204 (0%)	0
Injury, poisoning and procedural complications
Hip fracture	1/407 (0.2%)	1	0/204 (0%)	0
Joint dislocation	1/407 (0.2%)	1	0/204 (0%)	0
Overdose	1/407 (0.2%)	1	0/204 (0%)	0
Spinal compression fracture	1/407 (0.2%)	1	0/204 (0%)	0
Upper limb fracture	0/407 (0%)	0	1/204 (0.5%)	1
Metabolism and nutrition disorders
Hypokalaemia	1/407 (0.2%)	1	0/204 (0%)	0
Obesity	0/407 (0%)	0	1/204 (0.5%)	1
Musculoskeletal and connective tissue disorders
Back pain	1/407 (0.2%)	1	0/204 (0%)	0
Cervical spinal stenosis	2/407 (0.5%)	2	0/204 (0%)	0
Intervertebral disc protrusion	1/407 (0.2%)	1	0/204 (0%)	0
Osteoarthritis	3/407 (0.7%)	4	0/204 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	1/407 (0.2%)	1	0/204 (0%)	0
Castleman's disease	0/407 (0%)	0	1/204 (0.5%)	1
Invasive lobular breast carcinoma	0/407 (0%)	0	1/204 (0.5%)	1
Papillary thyroid cancer	1/407 (0.2%)	1	0/204 (0%)	0
Uterine leiomyoma	1/407 (0.2%)	1	0/204 (0%)	0
Nervous system disorders
Cerebral infarction	1/407 (0.2%)	1	0/204 (0%)	0
Syncope	1/407 (0.2%)	1	0/204 (0%)	0
Transient ischaemic attack	1/407 (0.2%)	1	0/204 (0%)	0
Psychiatric disorders
Anxiety	1/407 (0.2%)	1	0/204 (0%)	0
Renal and urinary disorders
Hydronephrosis	1/407 (0.2%)	1	0/204 (0%)	0
Nephrolithiasis	1/407 (0.2%)	1	0/204 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/407 (0.2%)	1	0/204 (0%)	0
Surgical and medical procedures
Neck dissection	1/407 (0.2%)	1	0/204 (0%)	0
Vascular disorders
Deep vein thrombosis	1/407 (0.2%)	1	0/204 (0%)	0
Other (Not Including Serious) Adverse Events
	Semaglutide 2.4 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	379/407 (93.1%)		177/204 (86.8%)
Gastrointestinal disorders
Abdominal distension	41/407 (10.1%)	55	20/204 (9.8%)	28
Abdominal pain	53/407 (13%)	75	10/204 (4.9%)	11
Abdominal pain upper	33/407 (8.1%)	45	5/204 (2.5%)	5
Constipation	150/407 (36.9%)	210	50/204 (24.5%)	62
Diarrhoea	147/407 (36.1%)	307	45/204 (22.1%)	62
Dyspepsia	36/407 (8.8%)	47	10/204 (4.9%)	15
Eructation	36/407 (8.8%)	52	1/204 (0.5%)	1
Flatulence	47/407 (11.5%)	62	23/204 (11.3%)	24
Gastrooesophageal reflux disease	25/407 (6.1%)	32	4/204 (2%)	4
Nausea	237/407 (58.2%)	511	45/204 (22.1%)	60
Vomiting	111/407 (27.3%)	212	22/204 (10.8%)	25
General disorders
Fatigue	52/407 (12.8%)	69	15/204 (7.4%)	19
Immune system disorders
Seasonal allergy	12/407 (2.9%)	18	11/204 (5.4%)	14
Infections and infestations
Gastroenteritis	28/407 (6.9%)	32	12/204 (5.9%)	19
Gastroenteritis viral	41/407 (10.1%)	46	13/204 (6.4%)	13
Influenza	27/407 (6.6%)	32	11/204 (5.4%)	11
Nasopharyngitis	90/407 (22.1%)	128	49/204 (24%)	70
Sinusitis	39/407 (9.6%)	51	26/204 (12.7%)	34
Upper respiratory tract infection	85/407 (20.9%)	115	44/204 (21.6%)	65
Urinary tract infection	41/407 (10.1%)	60	10/204 (4.9%)	11
Metabolism and nutrition disorders
Decreased appetite	35/407 (8.6%)	36	7/204 (3.4%)	7
Musculoskeletal and connective tissue disorders
Arthralgia	39/407 (9.6%)	54	19/204 (9.3%)	23
Back pain	53/407 (13%)	67	22/204 (10.8%)	24
Pain in extremity	17/407 (4.2%)	17	13/204 (6.4%)	14
Nervous system disorders
Dizziness	52/407 (12.8%)	73	11/204 (5.4%)	14
Headache	78/407 (19.2%)	123	20/204 (9.8%)	25
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	13/407 (3.2%)	17	12/204 (5.9%)	12

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.