STEP 4: Research Study Investigating How Well Semaglutide Works in People Suffering From Overweight or Obesity

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03548987
• Collaborator: (none)
• Enrollment: 902
• Locations: 72
• Arms: 2
• Actual Duration (Months): 21.5
• Patients Per Site: 12.5
• Patients Per Site Per Month: 0.6

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. In addition to taking the medicine, the participant will have talks with study staff about healthy food choices, how to be more physically active and what a participant can do to lose weight.

The participant will get semaglutide for the first 20 weeks. Then the participant will get either semaglutide or "dummy" medicine - which treatment the participant gets after the 20 weeks is decided by chance. The participants 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. The study will last for about 1.5 years.

Condition or Disease	Intervention/Treatment	Phase
Metabolism and Nutrition Disorder; Obesity	Drug: Semaglutide; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 902 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Sponsor staff involved in the clinical trial is masked according to company standard procedures.
• Primary Purpose: Treatment
• Official Title: Effect and Safety of Semaglutide 2.4 mg Once-weekly in Subjects With Overweight or Obesity Who Have Reached Target Dose During run-in Period
• Actual Study Start Date: Jun 4, 2018
• Actual Primary Completion Date: Feb 22, 2020
• Actual Study Completion Date: Mar 20, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Semaglutide Run-in Period: Participants will receive semaglutide at an escalating doses (0.25 mg, 0.5 mg, 1 mg, 1.7 mg, 2.4 mg) for 20 weeks (week 0 to week 20). The dose will be escalated to next level every 4 weeks. Maintenance period: Participants will be randomized to receive semaglutide injection for 48 weeks (from week 20 to week 68). The trial product will be administered as an adjunct to a reduced-calorie diet and increased physical activity during the trial period.	Drug: Semaglutide; Subcutaneous (under the skin) injection of semaglutide once-weekly.
Placebo Comparator: Placebo Run-in Period: Participants will receive semaglutide at an escalating doses (0.25 mg, 0.5 mg, 1 mg, 1.7 mg, 2.4 mg) for 20 weeks (week 0 to week 20). The dose will be escalated to next level every 4 weeks. Maintenance period: Participants will be randomized to receive semaglutide placebo injection for 48 weeks (from week 20 to week 68). The trial product will be administered as an adjunct to a reduced-calorie diet and increased physical activity during the trial period.	Drug: Semaglutide; Subcutaneous (under the skin) injection of semaglutide once-weekly.; Drug: Placebo; Subcutaneous (under the skin) injection of semaglutide placebo once-weekly.

Outcome Measures

Primary Outcome Measures

1. Change From Randomisation to Week 68 in Body Weight (%) [Randomisation (week 20) to week 68]

   Change in body weight from baseline (week 20) to week 68 is presented. 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 run-in (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).

Secondary Outcome Measures

1. Change in Waist Circumference [Randomization (week 20) to week 68]

   Change in waist circumference from baseline (week 20) 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 run-in (week 0) to last trial-related subject-site contact (week 75).

2. Change in Systolic Blood Pressure [Randomization (week 20) to week 68]

   Change in systolic blood pressure from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75).

3. Change in Diastolic Blood Pressure [Randomization (week 20) to week 68]

   Change in diastolic blood pressure from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75).

4. Change in Physical Functioning Score (Short Form 36 [SF-36]) [Randomization (week 20) 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 20 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 run-in (week 0) to last trial-related subject-site contact (week 75).

5. Change in Body Weight [Kilogram (Kg)] [Randomisation (week 20) to week 68]

   Change in body weight from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75).

6. Change in Body Mass Index (BMI) [Randomization (week 20) to week 68]

   Change in BMI from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75).

7. Change in Haemoglobin A1c (HbA1c) [%] [Randomization (week 20) to week 68]

   Change in HbA1c from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75).

8. Change in HbA1c [Millimoles Per Mole (mmol/Mol)] [Randomization (week 20) to week 68]

   Change in HbA1c from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75).

9. Change in Fasting Plasma Glucose [Milligrams Per Deciliter (mg/dL)] [Randomization (week 20) to week 68]

   Change in fasting plasma glucose from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75).

10. Change in Fasting Plasma Glucose [Millimoles Per Litre (mmol/L)] [Randomization (week 20) to week 68]

    Change in fasting plasma glucose from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75).

11. Change in Fasting Serum Insulin [Randomization (week 20) to week 68]

    Change in fasting serum insulin from baseline (week 20) 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 run-in (week 0) to last trial-related subject-site contact (week 75).

12. Change in Total Cholesterol [Randomization (week 20) to week 68]

    Change in fasting total cholesterol from baseline (week 20) to week 68 (measured as mmol/L) 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 run-in (week 0) to last trial-related subject-site contact (week 75).

13. Change in High-density Lipoproteins (HDL) [Randomization (week 20) to week 68]

    Change in fasting HDL from baseline (week 20) to week 68 (measured as mmol/L) 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 run-in (week 0) to last trial-related subject-site contact (week 75).

14. Change in Low-density Lipoproteins (LDL) [Randomization (week 20) to week 68]

    Change in fasting LDL from baseline (week 20) to week 68 (measured as mmol/L) 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 run-in (week 0) to last trial-related subject-site contact (week 75).

15. Change in Very Low-density Lipoproteins (VLDL) [Randomization (week 20) to week 68]

    Change in fasting VLDL from baseline (week 20) to week 68 (measured as mmol/L) 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 run-in (week 0) to last trial-related subject-site contact (week 75).

16. Change in Free Fatty Acids [Randomization (week 20) to week 68]

    Change in fasting free fatty acids from baseline (week 20) to week 68 (measured as mmol/L) 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 run-in (week 0) to last trial-related subject-site contact (week 75).

17. Change in Triglycerides [Randomization (week 20) to week 68]

    Change in fasting triglycerides from baseline (week 20) to week 68 (measured as mmol/L) 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 run-in (week 0) to last trial-related subject-site contact (week 75).

18. Subjects Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score [Randomisation (week 20) to week 68]

    The number of participants achieving at least a 4.3-point increase in SF-36 physical functioning score from baseline (week 20) to week 68 is presented. In the reported data, 'Yes' infers number of participants who have achieved 4.3 points of increase of the score and 'No' infers number of participants who have not achieved 4.3 points of increase of the score. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of run-in (week 0) to last trial-related subject-site contact (week 75).

19. Subjects Who Gain Weight (Yes/no) [Randomisation (week 20) to week 68]

    The number of participants with weight gain from the start of the randomised period (week 20) to week 68 is presented. In the reported data, 'Yes' infers number of participants who have gained weight and 'No' infers number of participants who have not gained weight. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of run-in (week 0) to last trial-related subject-site contact (week 75).

20. Change in Body Weight [Run-in (week 0) to week 68]

    The body weight change (%) 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 run-in (week 0) to last trial-related subject-site contact (week 75).

21. Subjects Who Achieve (Yes/no): Body Weight Reduction < 0% [Run-in (week 0) to week 68]

    The number of participants who achieved less than (<) 0% weight loss from week 0 to week 68 is presented. In the reported data, 'Yes' infers number of participants who have achieved <0% weight loss whereas 'No' infers number of participants who have not achieved <0% 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 run-in (week 0) to last trial-related subject-site contact (week 75).

22. Subjects Who Achieve (Yes/no): Body Weight Reduction ≥ 5% [Run-in (week 0) to week 68]

    The number of participants who achieved greater than or equal to (≥) 5% weight loss from week 0 to week 68 is presented. In the reported data, 'Yes' infers number of participants who have achieved ≥ 5% weight loss whereas 'No' infers number of participants who have not achieved ≥ 5% 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 run-in (week 0) to last trial-related subject-site contact (week 75).

23. Subjects Who Achieve (Yes/no): Body Weight Reduction ≥ 10% [Run-in (week 0) to week 68]

    The number of participants who achieved ≥ 10% weight loss from week 0 to week 68 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 run-in (week 0) to last trial-related subject-site contact (week 75).

24. Subjects Who Achieve (Yes/no): Body Weight Reduction ≥ 15% [Run-in (week 0) to week 68]

    The number of participants who achieved ≥ 15% weight loss from week 0 to week 68 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 run-in (week 0) to last trial-related subject-site contact (week 75).

25. Number of Treatment-emergent Adverse Events (AEs) [Run-in (week 0) to randomisation (week 20)]

    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 (week 0-20 run-in period). 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. Number of Treatment-emergent AEs [Randomisation (week 20) to week 75]

    An 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 TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to treatment (week 20-75). 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).

27. Number of Serious Adverse Events (SAEs) [Run-in (week 0) to randomisation (week 20)]

    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 during run-in period from week 0 to week 20 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).

28. Number of Serious Adverse Events (SAEs) [Randomisation (week 20) 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 during run-in period from week 0 to week 20 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).

29. Change in Pulse [Run-in (week 0) to randomisation (week 20)]

    Change in pulse rate from week 0 week to week 20 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).

30. Change in Pulse [Randomisation (week 20) to week 68]

    Change in pulse from week 20 and 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).

31. Change in Amylase [Run-in (week) 0 to randomization (week 20)]

    Change in amylase (measured as units per liter [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).

32. Change in Amylase [Randomisation (week 20) 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).

33. Change in Lipase [Run-in (week 0) to randomization (week 20)]

    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).

34. Change in Lipase [Randomisation (week 20) 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).

35. Change in Calcitonin [Run-in (week 0) to randomization (week 20)]

    Change in calcitonin (measured as nanogram per liter (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).

36. Change in Calcitonin [Randomisation (week 20) 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 greater than or equal to 18 years at the time of signing informed consent

• Body mass index greater than or equal to 30 kg/sqm or greater than or equal to 27 kg/sqm 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:

• Haemoglobin A1c greater than or equal to 48 mmol/mol (6.5%) as measured by 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	Anniston	Alabama	United States	36207
2	Novo Nordisk Investigational Site	Fresno	California	United States	93720
3	Novo Nordisk Investigational Site	San Diego	California	United States	92108
4	Novo Nordisk Investigational Site	Alpharetta	Georgia	United States	30022
5	Novo Nordisk Investigational Site	Roswell	Georgia	United States	30076
6	Novo Nordisk Investigational Site	Suwanee	Georgia	United States	30024
7	Novo Nordisk Investigational Site	Louisville	Kentucky	United States	40213
8	Novo Nordisk Investigational Site	Baton Rouge	Louisiana	United States	70808
9	Novo Nordisk Investigational Site	Elkridge	Maryland	United States	21075-6437
10	Novo Nordisk Investigational Site	Buckley	Michigan	United States	49620
11	Novo Nordisk Investigational Site	Omaha	Nebraska	United States	68198-3020
12	Novo Nordisk Investigational Site	New York	New York	United States	10016
13	Novo Nordisk Investigational Site	Greensboro	North Carolina	United States	27408
14	Novo Nordisk Investigational Site	Greenville	North Carolina	United States	27834
15	Novo Nordisk Investigational Site	Raleigh	North Carolina	United States	27612
16	Novo Nordisk Investigational Site	Salisbury	North Carolina	United States	28144
17	Novo Nordisk Investigational Site	Cincinnati	Ohio	United States	45242
18	Novo Nordisk Investigational Site	Dayton	Ohio	United States	45406
19	Novo Nordisk Investigational Site	Bristol	Tennessee	United States	37620-7352
20	Novo Nordisk Investigational Site	Bristol	Tennessee	United States	37620
21	Novo Nordisk Investigational Site	Chattanooga	Tennessee	United States	37404
22	Novo Nordisk Investigational Site	Austin	Texas	United States	78731
23	Novo Nordisk Investigational Site	Dallas	Texas	United States	75226
24	Novo Nordisk Investigational Site	Dallas	Texas	United States	75230
25	Novo Nordisk Investigational Site	Dallas	Texas	United States	75231
26	Novo Nordisk Investigational Site	Arlington	Virginia	United States	22206
27	Novo Nordisk Investigational Site	Richmond	Virginia	United States	23226
28	Novo Nordisk Investigational Site	Wenatchee	Washington	United States	98801-2028
29	Novo Nordisk Investigational Site	Frederiksberg C		Denmark	1958
30	Novo Nordisk Investigational Site	Køge		Denmark	4600
31	Novo Nordisk Investigational Site	Haifa		Israel	35152
32	Novo Nordisk Investigational Site	Jerusalem		Israel	91120
33	Novo Nordisk Investigational Site	Kfar Saba		Israel	44281
34	Novo Nordisk Investigational Site	Petah-Tikva		Israel	49372
35	Novo Nordisk Investigational Site	Tel Hashomer		Israel	52621
36	Novo Nordisk Investigational Site	Tel-Aviv		Israel	64239
37	Novo Nordisk Investigational Site	Amsterdam		Netherlands	1066 EC
38	Novo Nordisk Investigational Site	Amsterdam		Netherlands	1105 AZ
39	Novo Nordisk Investigational Site	Arnhem		Netherlands	6815 AD
40	Novo Nordisk Investigational Site	Braga		Portugal	4710-243
41	Novo Nordisk Investigational Site	Coimbra		Portugal	3000-561
42	Novo Nordisk Investigational Site	Matosinhos		Portugal	4464-513
43	Novo Nordisk Investigational Site	Porto		Portugal	4099-001
44	Novo Nordisk Investigational Site	Porto		Portugal	4200-319
45	Novo Nordisk Investigational Site	Vila Nova de Gaia		Portugal	4400-346
46	Novo Nordisk Investigational Site	Johannesburg	Gauteng	South Africa	2001
47	Novo Nordisk Investigational Site	Johannesburg	Gauteng	South Africa	2013
48	Novo Nordisk Investigational Site	Pretoria	Gauteng	South Africa	0181
49	Novo Nordisk Investigational Site	Pretoria	Gauteng	South Africa	0184
50	Novo Nordisk Investigational Site	Durban	KwaZulu-Natal	South Africa	4001
51	Novo Nordisk Investigational Site	Brits	North West	South Africa	0250
52	Novo Nordisk Investigational Site	Almeria		Spain	04009
53	Novo Nordisk Investigational Site	Madrid		Spain	28009
54	Novo Nordisk Investigational Site	Madrid		Spain	28040
55	Novo Nordisk Investigational Site	Sabadell		Spain	08208
56	Novo Nordisk Investigational Site	Sevilla		Spain	41003
57	Novo Nordisk Investigational Site	Sevilla		Spain	41009
58	Novo Nordisk Investigational Site	Sevilla		Spain	41013
59	Novo Nordisk Investigational Site	Malmö		Sweden	205 02
60	Novo Nordisk Investigational Site	Stockholm		Sweden	141 86
61	Novo Nordisk Investigational Site	Uppsala		Sweden	751 85
62	Novo Nordisk Investigational Site	Genève 14		Switzerland	1211
63	Novo Nordisk Investigational Site	Olten		Switzerland	4600
64	Novo Nordisk Investigational Site	St. Gallen		Switzerland	9007
65	Novo Nordisk Investigational Site	St. Gallen		Switzerland	9016
66	Novo Nordisk Investigational Site	Zollikerberg		Switzerland	8125
67	Novo Nordisk Investigational Site	Zürich		Switzerland	8091
68	Novo Nordisk Investigational Site	Kharkiv		Ukraine	61039
69	Novo Nordisk Investigational Site	Kyiv		Ukraine	03039
70	Novo Nordisk Investigational Site	Kyiv		Ukraine	04050
71	Novo Nordisk Investigational Site	Kyiv		Ukraine	04114
72	Novo Nordisk Investigational Site	Odesa		Ukraine	65059

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 - Jun 3, 2020
• Statistical Analysis Plan - Jun 25, 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: NCT03548987
• Other Study ID Numbers: NN9536-4376; U1111-1201-0898; 2017-003473-34
• First Posted: Jun 7, 2018
• Last Update Posted: Jan 19, 2022
• Last Verified: Jan 1, 2022

• 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; Nutrition Disorders; Overweight

Study Results

Participant Flow

Recruitment Details

The trial was conducted in 73 sites in Denmark (2), Israel (6), Netherlands (3), Portugal (6), South Africa (6), Spain (7), Sweden (4), Switzerland (6), Ukraine (5) and United States (28).

Pre-assignment Detail

The trial included 20-week run-in period and 48-week maintenance period. During the run-in period, participant started with a semaglutide dose of 0.25 mg and the dose was increased every fourth week until the target dose, 2.4 mg was reached. Out of 902 participants, 803 have completed the run-in period. Thus, these were randomised in 2:1 ratio either to receive semaglutide 2.4 mg or placebo. The treatment is an adjunct to reduced-calorie diet and increased physical activity.

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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.	Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Period Title: Run-in Period (Week 0 to Week 20)
STARTED	902	0
Safety Analysis Set (SAS)	902	0
COMPLETED	803	0
NOT COMPLETED	99	0
Period Title: Run-in Period (Week 0 to Week 20)
STARTED	535	268
Full Analysis Set (FAS)	535	268
COMPLETED	504	237
NOT COMPLETED	31	31

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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.	Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.	Total of all reporting groups
Overall Participants	535	268	803
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	47 (12)	46 (12)	46 (12)
Sex: Female, Male (Count of Participants)
Female	429 80.2%	205 76.5%	634 79%
Male	106 19.8%	63 23.5%	169 21%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	42 7.9%	21 7.8%	63 7.8%
Not Hispanic or Latino	493 92.1%	247 92.2%	740 92.2%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	15 2.8%	4 1.5%	19 2.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	69 12.9%	35 13.1%	104 13%
White	446 83.4%	226 84.3%	672 83.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	5 0.9%	3 1.1%	8 1%

Outcome Measures

1. Primary Outcome

Title	Change From Randomisation to Week 68 in Body Weight (%)
Description	Change in body weight from baseline (week 20) to week 68 is presented. 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 run-in (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	Randomisation (week 20) to week 68

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = FAS which comprised all randomised participants. Number 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.	Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Measure Participants	535	268
In-trial	-8.3 (8.1)	6.5 (7.7)
On-treatment	-8.8 (7.8)	6.1 (7.7)

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	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-14.75
	Confidence Interval	(2-Sided) 95%; -16.00 to -13.50
	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	Other
	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	-15.33
	Confidence Interval	(2-Sided) 95%; -16.52 to -14.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change in Waist Circumference
Description	Change in waist circumference from baseline (week 20) 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Randomization (week 20) 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.	Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Measure Participants	518	248
Mean (Standard Deviation) [Centimeter (cm)]	-6.9 (7.5)	3.2 (7.0)

3. Secondary Outcome

Title	Change in Systolic Blood Pressure
Description	Change in systolic blood pressure from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Randomization (week 20) 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.	Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Measure Participants	518	248
Mean (Standard Deviation) [Millimeters of mercury (mmHg)]	0 (14)	5 (13)

4. Secondary Outcome

Title	Change in Diastolic Blood Pressure
Description	Change in diastolic blood pressure from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Randomization (week 20) 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.	Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Measure Participants	518	248
Mean (Standard Deviation) [mmHg]	0 (9)	1 (9)

5. Secondary Outcome

Title	Change in Physical Functioning Score (Short Form 36 [SF-36])
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 20 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Randomization (week 20) 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.	Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Measure Participants	515	245
Change in physical functioning score (SF-36)	1.0 (3.8)	-1.2 (4.5)
Change in SF-36 role-physical score	0.3 (5.0)	-0.9 (5.3)
Change in SF-36 bodily pain score	0.5 (7.0)	-1.5 (7.7)
Change in SF-36 general health score	0.3 (5.2)	-1.8 (5.8)
Change in SF-36 vitality score	1.1 (7.1)	-2.1 (7.6)
Change in SF-36 social functioning score	0.1 (6.2)	-1.8 (6.9)
Change in SF-36 mental health score	0.2 (6.2)	-2.2 (7.6)
Change in SF-36 physical component summary	0.8 (4.9)	-0.9 (5.6)
Change in SF-36 mental component summary	0.0 (6.2)	-2.4 (8.5)
Change in SF-36 role-emotional score	0.0 (5.5)	-2.2 (7.0)

6. Secondary Outcome

Title	Change in Body Weight [Kilogram (Kg)]
Description	Change in body weight from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Randomisation (week 20) 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.	Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Measure Participants	520	250
Mean (Standard Deviation) [Kg]	-7.5 (7.6)	5.7 (6.7)

7. Secondary Outcome

Title	Change in Body Mass Index (BMI)
Description	Change in BMI from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Randomization (week 20) 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.	Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Measure Participants	520	250
Mean (Standard Deviation) [Kilogram per square meter (kg/sqm)]	-2.7 (2.7)	2.0 (2.4)

8. Secondary Outcome

Title	Change in Haemoglobin A1c (HbA1c) [%]
Description	Change in HbA1c from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Randomization (week 20) 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.	Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Measure Participants	515	246
Mean (Standard Deviation) [Percentage point of HbA1c]	-0.2 (0.3)	0.1 (0.2)

9. Secondary Outcome

Title	Change in HbA1c [Millimoles Per Mole (mmol/Mol)]
Description	Change in HbA1c from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Randomization (week 20) 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.	Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Measure Participants	515	246
Mean (Standard Deviation) [mmol/mol]	-1.7 (2.8)	1.2 (2.7)

10. Secondary Outcome

Title	Change in Fasting Plasma Glucose [Milligrams Per Deciliter (mg/dL)]
Description	Change in fasting plasma glucose from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Randomization (week 20) 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.	Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Measure Participants	511	242
Mean (Standard Deviation) [mg/dL]	-1.1 (8.6)	7.6 (10.0)

11. Secondary Outcome

Title	Change in Fasting Plasma Glucose [Millimoles Per Litre (mmol/L)]
Description	Change in fasting plasma glucose from week 20 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Randomization (week 20) 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.	Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Measure Participants	511	242
Mean (Standard Deviation) [mmol/L]	-0.1 (0.5)	0.4 (0.6)

12. Secondary Outcome

Title	Change in Fasting Serum Insulin
Description	Change in fasting serum insulin from baseline (week 20) 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Randomization (week 20) 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.	Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Measure Participants	498	240
Geometric Mean (Geometric Coefficient of Variation) [Ratio of fasting serum insulin]	0.81 (60.9)	1.03 (64.6)

13. Secondary Outcome

Title	Change in Total Cholesterol
Description	Change in fasting total cholesterol from baseline (week 20) to week 68 (measured as mmol/L) 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Randomization (week 20) 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.	Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Measure Participants	517	245
Geometric Mean (Geometric Coefficient of Variation) [Ratio of fasting total cholesterol]	1.05 (13.5)	1.11 (14.4)

14. Secondary Outcome

Title	Change in High-density Lipoproteins (HDL)
Description	Change in fasting HDL from baseline (week 20) to week 68 (measured as mmol/L) 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Randomization (week 20) 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.	Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Measure Participants	515	245
Geometric Mean (Geometric Coefficient of Variation) [Ratio of fasting HDL cholesterol]	1.18 (13.2)	1.18 (16.3)

15. Secondary Outcome

Title	Change in Low-density Lipoproteins (LDL)
Description	Change in fasting LDL from baseline (week 20) to week 68 (measured as mmol/L) 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Randomization (week 20) 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.	Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Measure Participants	517	245
Geometric Mean (Geometric Coefficient of Variation) [Ratio of fasting LDL cholesterol]	1.01 (19.8)	1.07 (21.3)

16. Secondary Outcome

Title	Change in Very Low-density Lipoproteins (VLDL)
Description	Change in fasting VLDL from baseline (week 20) to week 68 (measured as mmol/L) 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Randomization (week 20) 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.	Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Measure Participants	517	245
Geometric Mean (Geometric Coefficient of Variation) [Ratio of fasting VLDL]	0.94 (33.6)	1.12 (39.0)

17. Secondary Outcome

Title	Change in Free Fatty Acids
Description	Change in fasting free fatty acids from baseline (week 20) to week 68 (measured as mmol/L) 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Randomization (week 20) 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.	Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Measure Participants	498	240
Geometric Mean (Geometric Coefficient of Variation) [Ratio of fasting free fatty acids]	0.78 (79.4)	0.89 (73.1)

18. Secondary Outcome

Title	Change in Triglycerides
Description	Change in fasting triglycerides from baseline (week 20) to week 68 (measured as mmol/L) 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Randomization (week 20) 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.	Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Measure Participants	517	245
Geometric Mean (Geometric Coefficient of Variation) [Ratio of fasting triglycerides]	0.94 (33.9)	1.12 (39.4)

19. Secondary Outcome

Title	Subjects Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score
Description	The number of participants achieving at least a 4.3-point increase in SF-36 physical functioning score from baseline (week 20) to week 68 is presented. In the reported data, 'Yes' infers number of participants who have achieved 4.3 points of increase of the score and 'No' infers number of participants who have not achieved 4.3 points of increase of the score. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Randomisation (week 20) 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.	Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Measure Participants	515	245
Yes	58 10.8%	11 4.1%
No	457 85.4%	234 87.3%

20. Secondary Outcome

Title	Subjects Who Gain Weight (Yes/no)
Description	The number of participants with weight gain from the start of the randomised period (week 20) to week 68 is presented. In the reported data, 'Yes' infers number of participants who have gained weight and 'No' infers number of participants who have not gained weight. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Randomisation (week 20) 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.	Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Measure Participants	520	250
Yes	79 14.8%	206 76.9%
No	441 82.4%	44 16.4%

21. Secondary Outcome

Title	Change in Body Weight
Description	The body weight change (%) 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Run-in (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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.	Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Measure Participants	520	250
Mean (Standard Deviation) [Percentage point]	-17.7 (9.8)	-5.4 (7.3)

22. Secondary Outcome

Title	Subjects Who Achieve (Yes/no): Body Weight Reduction < 0%
Description	The number of participants who achieved less than (<) 0% weight loss from week 0 to week 68 is presented. In the reported data, 'Yes' infers number of participants who have achieved <0% weight loss whereas 'No' infers number of participants who have not achieved <0% 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Run-in (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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.	Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Measure Participants	520	250
Yes	22 4.1%	51 19%
No	498 93.1%	199 74.3%

23. Secondary Outcome

Title	Subjects Who Achieve (Yes/no): Body Weight Reduction ≥ 5%
Description	The number of participants who achieved greater than or equal to (≥) 5% weight loss from week 0 to week 68 is presented. In the reported data, 'Yes' infers number of participants who have achieved ≥ 5% weight loss whereas 'No' infers number of participants who have not achieved ≥ 5% 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Run-in (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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.	Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Measure Participants	520	250
Yes	461 86.2%	119 44.4%
No	59 11%	131 48.9%

24. Secondary Outcome

Title	Subjects Who Achieve (Yes/no): Body Weight Reduction ≥ 10%
Description	The number of participants who achieved ≥ 10% weight loss from week 0 to week 68 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Run-in (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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.	Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Measure Participants	520	250
Yes	411 76.8%	51 19%
No	109 20.4%	199 74.3%

25. Secondary Outcome

Title	Subjects Who Achieve (Yes/no): Body Weight Reduction ≥ 15%
Description	The number of participants who achieved ≥ 15% weight loss from week 0 to week 68 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 run-in (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Run-in (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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.	Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Measure Participants	520	250
Yes	331 61.9%	23 8.6%
No	189 35.3%	227 84.7%

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 (week 0-20 run-in period). 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	Run-in (week 0) to randomisation (week 20)

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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.	Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Measure Participants	902	0
Number [Events]	3775

27. Secondary Outcome

Title	Number of Treatment-emergent AEs
Description	An 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 TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to treatment (week 20-75). 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	Randomisation (week 20) to week 75

Outcome Measure Data

Analysis Population Description

SAS included all participants who received at least one dose of trial product. Only randomised subjects in the safety analysis set contribute.

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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.	Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Measure Participants	535	268
Number [Events]	1885	779

28. 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 during run-in period from week 0 to week 20 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	Run-in (week 0) to randomisation (week 20)

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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.	Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Measure Participants	902	0
Number [Events]	23

29. 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 during run-in period from week 0 to week 20 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	Randomisation (week 20) to week 75

Outcome Measure Data

Analysis Population Description

SAS included all participants who received at least one dose of trial product. Only randomised subjects in the safety analysis set contribute.

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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.	Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Measure Participants	535	268
Number [Events]	51	19

30. Secondary Outcome

Title	Change in Pulse
Description	Change in pulse rate from week 0 week to week 20 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	Run-in (week 0) to randomisation (week 20)

Outcome Measure Data

Analysis Population Description

SAS included all participants who received at least one dose of trial product. Only randomised subjects in the safety analysis set contribute.

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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.	Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Measure Participants	535	268
Mean (Standard Deviation) [beats per minute (bpm)]	5 (9)	5 (9)

31. Secondary Outcome

Title	Change in Pulse
Description	Change in pulse from week 20 and 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	Randomisation (week 20) to week 68

Outcome Measure Data

Analysis Population Description

SAS included all participants who received at least one dose of trial product. Only randomised subjects in the safety analysis set contribute. '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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.	Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Measure Participants	495	234
Mean (Standard Deviation) [bpm]	-2 (9)	-5 (10)

32. Secondary Outcome

Title	Change in Amylase
Description	Change in amylase (measured as units per liter [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	Run-in (week) 0 to randomization (week 20)

Outcome Measure Data

Analysis Population Description

SAS included all participants who received at least one dose of trial product. Only randomised subjects in the safety analysis set contribute.

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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.	Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Measure Participants	535	268
Geometric Mean (Geometric Coefficient of Variation) [Ratio of amylase]	1.06 (18.7)	1.02 (26.2)

33. 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	Randomisation (week 20) to week 68

Outcome Measure Data

Analysis Population Description

SAS included all participants who received at least one dose of trial product. Only randomised subjects in the safety analysis set contribute. '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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.	Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Measure Participants	494	233
Geometric Mean (Geometric Coefficient of Variation) [Ratio of amylase]	1.06 (19.9)	1.00 (24.9)

34. 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	Run-in (week 0) to randomization (week 20)

Outcome Measure Data

Analysis Population Description

SAS included all participants who received at least one dose of trial product. Only randomised subjects in the safety analysis set contribute.

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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.	Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Measure Participants	535	268
Geometric Mean (Geometric Coefficient of Variation) [Ratio of lipase]	1.44 (40.2)	1.39 (53.5)

35. 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	Randomisation (week 20) to week 68

Outcome Measure Data

Analysis Population Description

SAS included all participants who received at least one dose of trial product. Only randomised subjects in the safety analysis set contribute. '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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.	Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Measure Participants	494	233
Geometric Mean (Geometric Coefficient of Variation) [ratio of lipase]	0.94 (37.8)	0.68 (51.7)

36. Secondary Outcome

Title	Change in Calcitonin
Description	Change in calcitonin (measured as nanogram per liter (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	Run-in (week 0) to randomization (week 20)

Outcome Measure Data

Analysis Population Description

SAS included all participants who received at least one dose of trial product. Only randomised subjects in the safety analysis set contribute.

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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.	Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Measure Participants	535	268
Geometric Mean (Geometric Coefficient of Variation) [Ratio of Calcitonin]	0.98 (28.4)	0.96 (28.1)

37. 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	Randomisation (week 20) to week 68

Outcome Measure Data

Analysis Population Description

SAS included all participants who received at least one dose of trial product. Only randomised subjects in the safety analysis set contribute. '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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly semaglutide s.c 2.4 mg until week 68.	Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20, to receive once weekly placebo until week 68.
Measure Participants	491	233
Geometric Mean (Geometric Coefficient of Variation) [Ratio of Calcitonin]	1.00 (24.8)	0.95 (25.5)

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: Run-in Period		Semaglutide 2.4: Treatment Period		Placebo: Treatment Period
Arm/Group Description	Participants were to receive once-weekly 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 in run-in period (week 0 to week 20) with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached.		Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20. Thus, out of 803, 535 participants were continued to receive once weekly semaglutide s.c 2.4 mg until week 68.		Participants were to receive once-weekly 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 in 20 week run-in period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg and 2.4 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. The participants with target dose reached were randomised in 2:1 at week 20. Thus, out of 803, 268 participants were switched to receive once weekly placebo until week 68.
All Cause Mortality
	Semaglutide: Run-in Period		Semaglutide 2.4: Treatment Period		Placebo: Treatment Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/902 (0%)		1/535 (0.2%)		1/268 (0.4%)
Serious Adverse Events
	Semaglutide: Run-in Period		Semaglutide 2.4: Treatment Period		Placebo: Treatment Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/902 (2.3%)		41/535 (7.7%)		15/268 (5.6%)
Blood and lymphatic system disorders
Pancytopenia	0/902 (0%)	0	1/535 (0.2%)	1	0/268 (0%)	0
Cardiac disorders
Acute myocardial infarction	2/902 (0.2%)	2	0/535 (0%)	0	1/268 (0.4%)	1
Atrial fibrillation	0/902 (0%)	0	1/535 (0.2%)	1	2/268 (0.7%)	2
Supraventricular tachycardia	0/902 (0%)	0	1/535 (0.2%)	1	0/268 (0%)	0
Ear and labyrinth disorders
Vertigo	1/902 (0.1%)	1	1/535 (0.2%)	1	0/268 (0%)	0
Endocrine disorders
Hypothyroidism	0/902 (0%)	0	1/535 (0.2%)	1	0/268 (0%)	0
Gastrointestinal disorders
Abdominal pain	2/902 (0.2%)	2	1/535 (0.2%)	1	1/268 (0.4%)	1
Constipation	0/902 (0%)	0	0/535 (0%)	0	1/268 (0.4%)	1
Diverticular perforation	0/902 (0%)	0	0/535 (0%)	0	1/268 (0.4%)	1
Intestinal obstruction	0/902 (0%)	0	0/535 (0%)	0	1/268 (0.4%)	1
Nausea	0/902 (0%)	0	1/535 (0.2%)	1	0/268 (0%)	0
Vomiting	0/902 (0%)	0	1/535 (0.2%)	1	0/268 (0%)	0
General disorders
Death	0/902 (0%)	0	1/535 (0.2%)	1	0/268 (0%)	0
Non-cardiac chest pain	0/902 (0%)	0	1/535 (0.2%)	1	0/268 (0%)	0
Hepatobiliary disorders
Biliary cyst	1/902 (0.1%)	1	0/535 (0%)	0	0/268 (0%)	0
Cholecystitis	0/902 (0%)	0	1/535 (0.2%)	1	0/268 (0%)	0
Cholelithiasis	0/902 (0%)	0	5/535 (0.9%)	5	2/268 (0.7%)	2
Infections and infestations
Abscess neck	1/902 (0.1%)	1	0/535 (0%)	0	0/268 (0%)	0
Appendicitis	0/902 (0%)	0	1/535 (0.2%)	1	1/268 (0.4%)	1
Cellulitis	1/902 (0.1%)	1	0/535 (0%)	0	0/268 (0%)	0
Diverticulitis	0/902 (0%)	0	1/535 (0.2%)	1	0/268 (0%)	0
Gastroenteritis	0/902 (0%)	0	2/535 (0.4%)	2	0/268 (0%)	0
Induced abortion infection	0/902 (0%)	0	0/535 (0%)	0	1/268 (0.4%)	1
Pertussis	0/902 (0%)	0	1/535 (0.2%)	1	0/268 (0%)	0
Pyelonephritis acute	0/902 (0%)	0	1/535 (0.2%)	1	0/268 (0%)	0
Tooth abscess	0/902 (0%)	0	0/535 (0%)	0	1/268 (0.4%)	1
Urinary tract infection	0/902 (0%)	0	0/535 (0%)	0	1/268 (0.4%)	1
Injury, poisoning and procedural complications
Ankle fracture	0/902 (0%)	0	0/535 (0%)	0	1/268 (0.4%)	1
Arthropod bite	1/902 (0.1%)	1	0/535 (0%)	0	0/268 (0%)	0
Corneal abrasion	1/902 (0.1%)	1	0/535 (0%)	0	0/268 (0%)	0
Fall	0/902 (0%)	0	1/535 (0.2%)	1	0/268 (0%)	0
Incisional hernia	0/902 (0%)	0	1/535 (0.2%)	1	0/268 (0%)	0
Lower limb fracture	1/902 (0.1%)	1	0/535 (0%)	0	0/268 (0%)	0
Meniscus injury	0/902 (0%)	0	1/535 (0.2%)	1	1/268 (0.4%)	1
Post lumbar puncture syndrome	0/902 (0%)	0	1/535 (0.2%)	1	0/268 (0%)	0
Road traffic accident	0/902 (0%)	0	0/535 (0%)	0	1/268 (0.4%)	1
Spinal compression fracture	0/902 (0%)	0	1/535 (0.2%)	1	0/268 (0%)	0
Metabolism and nutrition disorders
Dehydration	1/902 (0.1%)	1	0/535 (0%)	0	0/268 (0%)	0
Type 2 diabetes mellitus	0/902 (0%)	0	1/535 (0.2%)	1	0/268 (0%)	0
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	0/902 (0%)	0	1/535 (0.2%)	1	0/268 (0%)	0
Osteoarthritis	3/902 (0.3%)	3	0/535 (0%)	0	0/268 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Endometrial adenocarcinoma	0/902 (0%)	0	1/535 (0.2%)	1	0/268 (0%)	0
Endometrial cancer stage II	1/902 (0.1%)	1	0/535 (0%)	0	0/268 (0%)	0
Haemangioma	0/902 (0%)	0	1/535 (0.2%)	1	0/268 (0%)	0
Intraductal proliferative breast lesion	0/902 (0%)	0	1/535 (0.2%)	1	0/268 (0%)	0
Invasive breast carcinoma	0/902 (0%)	0	1/535 (0.2%)	1	0/268 (0%)	0
Invasive ductal breast carcinoma	0/902 (0%)	0	1/535 (0.2%)	1	0/268 (0%)	0
Lung cancer metastatic	0/902 (0%)	0	0/535 (0%)	0	1/268 (0.4%)	1
Malignant melanoma	0/902 (0%)	0	1/535 (0.2%)	1	0/268 (0%)	0
Marginal zone lymphoma	0/902 (0%)	0	1/535 (0.2%)	1	0/268 (0%)	0
Uterine leiomyoma	0/902 (0%)	0	1/535 (0.2%)	1	0/268 (0%)	0
Nervous system disorders
Carotid sinus syndrome	0/902 (0%)	0	0/535 (0%)	0	1/268 (0.4%)	1
Hemiparaesthesia	1/902 (0.1%)	1	0/535 (0%)	0	0/268 (0%)	0
Hemiparesis	0/902 (0%)	0	1/535 (0.2%)	1	0/268 (0%)	0
Migraine	0/902 (0%)	0	2/535 (0.4%)	2	0/268 (0%)	0
Paraesthesia	0/902 (0%)	0	1/535 (0.2%)	2	0/268 (0%)	0
Quadriplegia	0/902 (0%)	0	1/535 (0.2%)	1	0/268 (0%)	0
Syncope	1/902 (0.1%)	1	0/535 (0%)	0	0/268 (0%)	0
Transient global amnesia	0/902 (0%)	0	1/535 (0.2%)	1	0/268 (0%)	0
Pregnancy, puerperium and perinatal conditions
Morning sickness	0/902 (0%)	0	1/535 (0.2%)	1	0/268 (0%)	0
Product Issues
Lead dislodgement	0/902 (0%)	0	1/535 (0.2%)	1	0/268 (0%)	0
Renal and urinary disorders
Nephrolithiasis	2/902 (0.2%)	2	1/535 (0.2%)	1	0/268 (0%)	0
Ureterolithiasis	0/902 (0%)	0	1/535 (0.2%)	1	0/268 (0%)	0
Reproductive system and breast disorders
Menorrhagia	0/902 (0%)	0	0/535 (0%)	0	1/268 (0.4%)	1
Ovarian cyst	1/902 (0.1%)	1	0/535 (0%)	0	0/268 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/902 (0.1%)	1	0/535 (0%)	0	0/268 (0%)	0
Surgical and medical procedures
Arthroscopic surgery	1/902 (0.1%)	1	0/535 (0%)	0	0/268 (0%)	0
Orthognathic surgery	0/902 (0%)	0	1/535 (0.2%)	1	0/268 (0%)	0
Vascular disorders
Hypertension	0/902 (0%)	0	1/535 (0.2%)	1	0/268 (0%)	0
Hypotension	0/902 (0%)	0	1/535 (0.2%)	1	0/268 (0%)	0
Other (Not Including Serious) Adverse Events
	Semaglutide: Run-in Period		Semaglutide 2.4: Treatment Period		Placebo: Treatment Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	670/902 (74.3%)		295/535 (55.1%)		114/268 (42.5%)
Gastrointestinal disorders
Abdominal distension	50/902 (5.5%)	53	8/535 (1.5%)	10	2/268 (0.7%)	2
Abdominal pain	67/902 (7.4%)	82	34/535 (6.4%)	45	8/268 (3%)	9
Abdominal pain upper	49/902 (5.4%)	64	20/535 (3.7%)	22	3/268 (1.1%)	3
Constipation	200/902 (22.2%)	232	62/535 (11.6%)	75	16/268 (6%)	18
Diarrhoea	212/902 (23.5%)	309	77/535 (14.4%)	114	19/268 (7.1%)	26
Dyspepsia	103/902 (11.4%)	127	9/535 (1.7%)	9	2/268 (0.7%)	2
Eructation	71/902 (7.9%)	88	14/535 (2.6%)	15	1/268 (0.4%)	1
Flatulence	50/902 (5.5%)	73	14/535 (2.6%)	44	3/268 (1.1%)	4
Gastrooesophageal reflux disease	58/902 (6.4%)	60	5/535 (0.9%)	6	1/268 (0.4%)	1
Nausea	422/902 (46.8%)	629	75/535 (14%)	104	13/268 (4.9%)	13
Vomiting	140/902 (15.5%)	239	54/535 (10.1%)	87	8/268 (3%)	13
General disorders
Fatigue	67/902 (7.4%)	69	26/535 (4.9%)	29	6/268 (2.2%)	6
Infections and infestations
Influenza	28/902 (3.1%)	28	39/535 (7.3%)	45	19/268 (7.1%)	23
Nasopharyngitis	92/902 (10.2%)	102	58/535 (10.8%)	77	39/268 (14.6%)	54
Metabolism and nutrition disorders
Decreased appetite	102/902 (11.3%)	115	7/535 (1.3%)	7	0/268 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	21/902 (2.3%)	23	25/535 (4.7%)	28	14/268 (5.2%)	16
Back pain	26/902 (2.9%)	28	28/535 (5.2%)	32	18/268 (6.7%)	19
Nervous system disorders
Headache	96/902 (10.6%)	119	41/535 (7.7%)	48	10/268 (3.7%)	10

Limitations/Caveats

[Not Specified]

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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.