STEP 1: 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: NCT03548935
• Collaborator: (none)
• Enrollment: 1,961
• Locations: 128
• Arms: 2
• Actual Duration (Months): 33
• Patients Per Site: 15.3
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

This study will look at the change in participants' body weight from the start to the end of the study. The weight loss in participants taking semaglutide (a new medicine) will be compared to the weight loss of participants taking "dummy" medicine. In addition to taking the medicine, participants will have talks with study staff about healthy food choices, how to be more physically active and what you can do to lose weight. Participants will either get semaglutide or "dummy" medicine - which treatment participants get, is decided by chance. 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 has two phases: A main phase and an extension phase.The main phase will last for about 1.5 years. Participants will have 15 clinic visits and 10 phone calls with the study doctor. Extension phase: Approximately 300 participants will continue in the extension phase in the following countries only: Canada, Germany, the UK and selected sites in the US and Japan. These participants will be in the study for about 2.5 years.They will not receive treatment, but will attend another 5 follow-up visits with the study doctor.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 1961 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
• Actual Study Start Date: Jun 4, 2018
• Actual Primary Completion Date: Mar 30, 2020
• Actual Study Completion Date: Mar 5, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Semaglutide s.c. 2.4 mg once weekly Participants will receive semaglutide for 68 weeks.	Drug: Semaglutide; Participants will receive semaglutide subcutaneous (s.c.; under the skin) injection(s) once-weekly as well as diet and physical activity counselling for 68 weeks. Dose escalation of semaglutide will take place as follows: 0.25 mg from week 1 to 4, 0.5 mg from week 5 to 8, 1.0 mg from week 9 to 12, 1.7 mg from week 13 to 16 and 2.4 mg from week 17 to week 68.
Placebo Comparator: Semaglutide placebo Participants will receive semaglutide matching placebo for 68 weeks.	Drug: Placebo (semaglutide); Participants will receive semaglutide matching placebo s.c. injection(s) once-weekly as well as diet and physical activity counselling for 68 weeks.

Outcome Measures

Primary Outcome Measures

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

   Change in body weight from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from both in-trial and on-treatment observation periods. In-trial observation period: the uninterrupted time interval from date of randomization (week 0) to date of last contact with trial site (week 75). On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68), including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).

2. Participants Who Achieve 5 or More Percent Body Weight Reduction (Yes/no) [After week 68]

   Number of participants who achieved weight loss more than or equal to 5% (yes/no) at week 68 are 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 randomization (week 0) to last trial-related subject-site contact (week 75). On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68), including 2 weeks of follow-up. It excludes any period of temporary treatment interruption.

Secondary Outcome Measures

1. Subjects Who Achieve 10 or More Percent Body Weight Reduction (Yes/no) [Week 68]

   Number of participants who achieved weight loss more than or equal to (≥) 10% at 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 date of randomization (week 0) to date of last contact with trial site (week 75).

2. Participants Who Achieve 15 or More Percent Body Weight Reduction (Yes/no) [Week 68]

   Number of participants who achieved more than or equal to (≥) 15% weight loss at 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 randomization (week 0) to last trial-related subject-site contact (week 75).

3. Participants Who Achieve 20 or More Percent Body Weight Reduction (Yes/no) [Week 68]

   Number of participants who achieved more than or equal to (≥) 20% weight loss at 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 randomization (week 0) to last trial-related subject-site contact (week 75).

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

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

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

   Change in systolic blood pressure from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to date of last contact with trial site (week 75).

6. Change in Short Form 36 (SF-36) [Baseline (week 0) to week 68]

   SF-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ questionnaire measured eight domains of functional health and well-being as well as two component summary scores (physical component summary and mental component summary). In the metric of norm-based scores, 50 and 10 corresponds to the mean and standard deviation, respectively, for the 2009 US general population. Change from week 0 in the domain scores and component summary scores were evaluated at week 68. A positive change score indicates an improvement since baseline. These endpoints were evaluated based on the data from in-trial observation period which is the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).

7. Change in Impact of Weight on Quality of Life-Lite for Clinical Trial (IWQoL-Lite for CT) Score [Baseline (week 0) to week 68]

   IWQoL-Lite for CT is a modified version of an instrument designed to assess weight-related quality of life. It is used to assess the impact of body weight changes on patients' physical and psychosocial functioning in three composite scores (physical function, physical and psychosocial) and a total score. The scores range between 0-100 where higher scores indicate a better quality of life. 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 randomization (week 0) to last trial-related subject-site contact (week 75).

8. Change in Body Weight (kg) [Baseline (week 0) to week 68]

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

9. Change in Body Mass Index (BMI) (kg/m2) [Baseline (week 0) to week 68]

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

10. Change in HbA1C (%) [Baseline (week 0) to week 68]

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

11. Change in HbA1C (mmol/Mol) [Baseline (week 0) to week 68]

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

12. Change in Fasting Plasma Glucose (FPG) (mg/dL) [Baseline (week 0) to week 68]

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

13. Change in Fasting Serum Insulin (mIU/L) - Ratio to Baseline [Baseline (week 0) to week 68]

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

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

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

15. Change in Total Cholesterol (mg/dL) - Ratio to Baseline [Baseline (week 0) to week 68]

    Change in fasting total cholesterol from baseline (week 0) to week 68 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 randomization (week 0) to last trial-related subject-site contact (week 75).

16. Change in High-density Lipoproteins (HDL) (mg/dL) - Ratio to Baseline [Baseline (week 0) to week 68]

    Change in fasting HDL from baseline (week 0) to week 68 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 randomization (week 0) to last trial-related subject-site contact (week 75).

17. Change in Low-density Lipoproteins (LDL) (mg/dL) - Ratio to Baseline [Baseline (week 0) to week 68]

    Change in fasting LDL from baseline (week 0) to week 68 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 randomization (week 0) to last trial-related subject-site contact (week 75).

18. Change in Very Low-density Lipoproteins (VLDL) (mg/dL) - Ratio to Baseline [Baseline (week 0) to week 68]

    Change in fasting VLDL from baseline (week 0) to week 68 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 randomization (week 0) to last trial-related subject-site contact (week 75).

19. Change in Free Fatty Acids (mg/dL) - Ratio to Baseline [Baseline (week 0) to week 68]

    Change in fasting free fatty acids from baseline (week 0) to week 68 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 randomization (week 0) to last trial-related subject-site contact (week 75).

20. Change in Triglycerides (mg/dL) - Ratio to Baseline [Baseline (week 0) to week 68]

    Change in fasting triglycerides from baseline (week 0) to week 68 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 randomization (week 0) to last trial-related subject-site contact (week 75).

21. Change in High Sensitivity C-Reactive Protein (hsCRP) - (mg/L) - Ratio to Baseline [Baseline (week 0) to week 68]

    Change in high sensitivity C-reactive protein from baseline (week 0) to week 68 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 randomization (week 0) to last trial-related subject-site contact (week 75).

22. Change in Plasminogen Activator Inhibitor-1 (PAI-1) Activity (AU/ml) - Ratio to Baseline [Baseline (week 0) to week 68]

    Change in plasminogen activator inhibitor-1 activity from baseline (week 0) to week 68 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 randomization (week 0) to last trial-related subject-site contact (week 75).

23. Change in Soluble Leptin Receptor (ng/mL) - Ratio to Baseline [Baseline (week 0) to week 68]

    Change in soluble leptin receptor from baseline (week 0) to week 68 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 randomization (week 0) to last trial-related subject-site contact (week 75).

24. Change in Leptin (ng/mL) - Ratio to Baseline [Baseline (week 0) to week 68]

    Change in leptin from baseline (week 0) to week 68 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 randomization (week 0) to last trial-related subject-site contact (week 75).

25. Change in Body Composition (Total Fat Mass) (%) [Baseline (week 0) to week 68]

    Change in body composition (total fat mass) from baseline (week 0) to week 68 is presented. Body composition was assessed using Dual Energy X-ray Absorpmetry (DEXA). The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).

26. Change in Body Composition (Total Fat Mass) (kg) [Baseline (week 0) to week 68]

    Change in body composition (total fat mass) from baseline (week 0) to week 68 is presented. Body composition was assessed using Dual Energy X-ray Absorpmetry (DEXA). The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).

27. Change in Body Composition (Lean Body Mass) (%) [Baseline (week 0) to week 68]

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

28. Change in Body Composition (Lean Body Mass) (kg) [Baseline (week 0) to week 68]

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

29. Change in Body Composition (Visceral Fat Mass) (%) [Baseline (week 0) to week 68]

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

30. Change in Body Composition (Visceral Fat Mass) (kg) [Baseline (week 0) to week 68]

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

31. Change in Body Weight (%) - DEXA Subpopulation [Baseline (week 0) to week 68]

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

32. Change in Body Weight (kg) - DEXA Subpopulation [Baseline (week 0) to week 68]

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

33. Participants Who Achieve "Responder Definition Value" (Yes/no) for SF-36 Physical Functioning Score [After week 68]

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

34. Participants Who Achieve "Responder Definition Value" (Yes/no) for IWQoL-Lite for CT Physical Function Domain (5-items) Score [After week 68]

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

35. Number of Treatment Emergent Adverse Events (TEAEs) [Baseline (week 0) to week 75]

    An adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. All AEs mentioned here are treatment emergent adverse events (TEAE) defined as an event for which the onset of the event occurs in the on-treatment 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).

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

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

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

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

38. Change in Amylase - Ratio to Baseline [Baseline (week 0) to week 68]

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

39. Change in Lipase - Ratio to Baseline [Baseline (week 0) to week 68]

    Change in lipase (measured as units per litre [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).

40. Change in Calcitonin - Ratio to Baseline [Baseline (week 0) to week 68]

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

Eligibility Criteria

Criteria

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

Inclusion Criteria:

Main phase:

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

• Body mass index (BMI) greater than or equal to 30.0 kg/sqm or greater than or equal to 27.0 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

Extension phase:

• Informed consent for the extension phase obtained before any trial related activities for the extension phase

• On randomised treatment on the target dose at week 68, i.e. treated with 2.4 mg semaglutide once-weekly or semaglutide placebo

Exclusion Criteria:

Main phase:

• Glycated haemoglobin (HbA1C) greater than or equal to 48 mmol/mol (6.5%) as measured by the central laboratory at screening

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

Extension phase:

• Female who is pregnant or intends to become pregnant during the extension phase

• Any disorder, unwillingness or inability, not covered by any of the other exclusion criteria, which in the investigator's opinion, might jeopardise the subject's compliance with the extension of the trial

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	Anaheim	California	United States	92801
3	Novo Nordisk Investigational Site	Lomita	California	United States	90717
4	Novo Nordisk Investigational Site	Spring Valley	California	United States	91978
5	Novo Nordisk Investigational Site	Aurora	Colorado	United States	80045
6	Novo Nordisk Investigational Site	Waterbury	Connecticut	United States	06708
7	Novo Nordisk Investigational Site	Chiefland	Florida	United States	32626
8	Novo Nordisk Investigational Site	Crystal River	Florida	United States	34429
9	Novo Nordisk Investigational Site	Jacksonville	Florida	United States	32205
10	Novo Nordisk Investigational Site	Jacksonville	Florida	United States	32216
11	Novo Nordisk Investigational Site	Ocala	Florida	United States	34470
12	Novo Nordisk Investigational Site	Panama City	Florida	United States	32401
13	Novo Nordisk Investigational Site	Plantation	Florida	United States	33324
14	Novo Nordisk Investigational Site	Ponte Vedra	Florida	United States	32081
15	Novo Nordisk Investigational Site	Roswell	Georgia	United States	30076
16	Novo Nordisk Investigational Site	Chicago	Illinois	United States	60607
17	Novo Nordisk Investigational Site	Chicago	Illinois	United States	60611
18	Novo Nordisk Investigational Site	Indianapolis	Indiana	United States	46260
19	Novo Nordisk Investigational Site	Topeka	Kansas	United States	66606
20	Novo Nordisk Investigational Site	Louisville	Kentucky	United States	40213
21	Novo Nordisk Investigational Site	Buckley	Michigan	United States	49620
22	Novo Nordisk Investigational Site	Saint Peters	Missouri	United States	63303
23	Novo Nordisk Investigational Site	Butte	Montana	United States	59701
24	Novo Nordisk Investigational Site	Omaha	Nebraska	United States	68105
25	Novo Nordisk Investigational Site	Rochester	New York	United States	14609
26	Novo Nordisk Investigational Site	Salisbury	North Carolina	United States	28144
27	Novo Nordisk Investigational Site	Wilmington	North Carolina	United States	28401
28	Novo Nordisk Investigational Site	West Reading	Pennsylvania	United States	19611
29	Novo Nordisk Investigational Site	Charleston	South Carolina	United States	29425
30	Novo Nordisk Investigational Site	Simpsonville	South Carolina	United States	29681
31	Novo Nordisk Investigational Site	Nashville	Tennessee	United States	37212-1150
32	Novo Nordisk Investigational Site	Austin	Texas	United States	78749
33	Novo Nordisk Investigational Site	Dallas	Texas	United States	75226
34	Novo Nordisk Investigational Site	Dallas	Texas	United States	75230
35	Novo Nordisk Investigational Site	Dallas	Texas	United States	75234
36	Novo Nordisk Investigational Site	Round Rock	Texas	United States	78681
37	Novo Nordisk Investigational Site	Bountiful	Utah	United States	84010
38	Novo Nordisk Investigational Site	Richmond	Virginia	United States	23294
39	Novo Nordisk Investigational Site	Renton	Washington	United States	98057
40	Novo Nordisk Investigational Site	Caba		Argentina	C1093AAS
41	Novo Nordisk Investigational Site	Ciudad de Buenos Aires		Argentina	C1204AAD
42	Novo Nordisk Investigational Site	Corrientes		Argentina	3400
43	Novo Nordisk Investigational Site	Córdoba		Argentina	X5006IKK
44	Novo Nordisk Investigational Site	Santa Rosa		Argentina	6300
45	Novo Nordisk Investigational Site	Boussu		Belgium	7300
46	Novo Nordisk Investigational Site	Bruxelles		Belgium	1200
47	Novo Nordisk Investigational Site	Edegem		Belgium	2650
48	Novo Nordisk Investigational Site	Leuven		Belgium	3000
49	Novo Nordisk Investigational Site	Liège		Belgium	4000
50	Novo Nordisk Investigational Site	Plovdiv		Bulgaria	4002
51	Novo Nordisk Investigational Site	Sofia		Bulgaria	1431
52	Novo Nordisk Investigational Site	Sofia		Bulgaria	1606
53	Novo Nordisk Investigational Site	Sofia		Bulgaria	1797
54	Novo Nordisk Investigational Site	Edmonton	Alberta	Canada	T6H 2L4
55	Novo Nordisk Investigational Site	Surrey	British Columbia	Canada	V3Z 2N6
56	Novo Nordisk Investigational Site	Hamilton	Ontario	Canada	L8L 5G8
57	Novo Nordisk Investigational Site	North York	Ontario	Canada	M2M 4J5
58	Novo Nordisk Investigational Site	Toronto	Ontario	Canada	M4P 1P2
59	Novo Nordisk Investigational Site	Quebec		Canada	G1V 4G2
60	Novo Nordisk Investigational Site	Quebec		Canada	G1V 4G5
61	Novo Nordisk Investigational Site	Aarhus N		Denmark	8200
62	Novo Nordisk Investigational Site	Oulu		Finland	90220
63	Novo Nordisk Investigational Site	University Of Helsinki		Finland	00014
64	Novo Nordisk Investigational Site	Le Coudray		France	28630
65	Novo Nordisk Investigational Site	Narbonne		France	11108
66	Novo Nordisk Investigational Site	PARIS cedex 13		France	75651
67	Novo Nordisk Investigational Site	Paris		France	75908
68	Novo Nordisk Investigational Site	Pessac		France	33600
69	Novo Nordisk Investigational Site	Pierre Benite		France	69310
70	Novo Nordisk Investigational Site	Venissieux		France	69200
71	Novo Nordisk Investigational Site	Berlin		Germany	12627
72	Novo Nordisk Investigational Site	Bochum		Germany	44787
73	Novo Nordisk Investigational Site	Essen		Germany	45136
74	Novo Nordisk Investigational Site	Essen		Germany	45219
75	Novo Nordisk Investigational Site	Falkensee		Germany	14612
76	Novo Nordisk Investigational Site	Frankfurt		Germany	60313
77	Novo Nordisk Investigational Site	Giessen		Germany	35392
78	Novo Nordisk Investigational Site	Hamburg		Germany	22607
79	Novo Nordisk Investigational Site	Hohenmölsen		Germany	06679
80	Novo Nordisk Investigational Site	Leipzig		Germany	04103
81	Novo Nordisk Investigational Site	Saint Ingbert-Oberwürzbach		Germany	66386
82	Novo Nordisk Investigational Site	Stuttgart		Germany	70378
83	Novo Nordisk Investigational Site	Wangen		Germany	88239
84	Novo Nordisk Investigational Site	Guntur	Andhra Pradesh	India	522001
85	Novo Nordisk Investigational Site	Secunderabad,	Andhra Pradesh	India	500003
86	Novo Nordisk Investigational Site	Surat	Gujarat	India	395002
87	Novo Nordisk Investigational Site	Rohtak	Haryana	India	124001
88	Novo Nordisk Investigational Site	Thiruvananthapuram	Kerala	India	695031
89	Novo Nordisk Investigational Site	Nagpur	Maharashtra	India	440003
90	Novo Nordisk Investigational Site	Pune	Maharashtra	India	411004
91	Novo Nordisk Investigational Site	Pune	Maharashtra	India	411021
92	Novo Nordisk Investigational Site	New Dehli	New Delhi	India	110029
93	Novo Nordisk Investigational Site	Chennai	Tamil Nadu	India	600116
94	Novo Nordisk Investigational Site	Kolkata	West Bengal	India	700054
95	Novo Nordisk Investigational Site	Hyderabad		India	500 012
96	Novo Nordisk Investigational Site	Ludhiana		India	141001
97	Novo Nordisk Investigational Site	Chiba-shi, Chiba		Japan	260-8677
98	Novo Nordisk Investigational Site	Suita-shi, Osaka		Japan	565-0853
99	Novo Nordisk Investigational Site	Tokyo		Japan	103-0027
100	Novo Nordisk Investigational Site	Tokyo		Japan	103-0028
101	Novo Nordisk Investigational Site	Tokyo		Japan	160-0008
102	Novo Nordisk Investigational Site	Guadalajara	Jalisco	Mexico	44670
103	Novo Nordisk Investigational Site	Hermosillo	Sonora	Mexico	83280
104	Novo Nordisk Investigational Site	Merida	Yucatan	Mexico	97070
105	Novo Nordisk Investigational Site	Gdynia		Poland	81-338
106	Novo Nordisk Investigational Site	Lodz		Poland	90-242
107	Novo Nordisk Investigational Site	Poznan		Poland	60-589
108	Novo Nordisk Investigational Site	Szczecin		Poland	70-376
109	Novo Nordisk Investigational Site	San Juan		Puerto Rico	00921
110	Novo Nordisk Investigational Site	Moscow		Russian Federation	117036
111	Novo Nordisk Investigational Site	Novosibirsk		Russian Federation	630099
112	Novo Nordisk Investigational Site	Novosibirsk		Russian Federation	630117
113	Novo Nordisk Investigational Site	Penza		Russian Federation	440026
114	Novo Nordisk Investigational Site	Saint-Petersburg		Russian Federation	194358
115	Novo Nordisk Investigational Site	Tomsk		Russian Federation	634041
116	Novo Nordisk Investigational Site	Voronezh		Russian Federation	394018
117	Novo Nordisk Investigational Site	Yaroslavl		Russian Federation	150003
118	Novo Nordisk Investigational Site	Taipei		Taiwan	100
119	Novo Nordisk Investigational Site	Bristol		United Kingdom	BS10 5NB
120	Novo Nordisk Investigational Site	Cambridge		United Kingdom	CB2 0QQ
121	Novo Nordisk Investigational Site	Coventry		United Kingdom	CV2 2DX
122	Novo Nordisk Investigational Site	Glasgow		United Kingdom	G31 2ER
123	Novo Nordisk Investigational Site	Liverpool		United Kingdom	L9 7AL
124	Novo Nordisk Investigational Site	London		United Kingdom	SE1 9RT
125	Novo Nordisk Investigational Site	London		United Kingdom	W1T 7HA
126	Novo Nordisk Investigational Site	Norwich		United Kingdom	NR4 7UQ
127	Novo Nordisk Investigational Site	Rotherham		United Kingdom	S65 1DA
128	Novo Nordisk Investigational Site	Taunton		United Kingdom	TA1 5DA

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 - Mar 29, 2019
• Statistical Analysis Plan - Jul 3, 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: NCT03548935
• Other Study ID Numbers: NN9536-4373; U1111-1200-8053; 2017-003436-36
• First Posted: Jun 7, 2018
• Last Update Posted: Nov 19, 2021
• Last Verified: Nov 1, 2021

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

Study Results

Participant Flow

Recruitment Details

The trial was conducted at 129 sites in 16 countries as follows (all sites screened and randomized): Argentina (5 sites), Belgium (5 sites), Bulgaria (5 sites), Canada (7 sites), Denmark (1 site), Finland (2 sites), France (7 sites), Germany (13 sites), India (13 sites), Japan (5 sites), Mexico (3 sites), Poland (4 sites), Russian Federation (8 sites), Taiwan(1 site), UK (10 sites), US (40 sites).

Pre-assignment Detail

The trial included an initial 16-week dose-escalation period and a 52-week dose maintenance period. Participants were randomized 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 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Period Title: Overall Study
STARTED	1306	655
Full Analysis Set (FAS)	1306	655
Safety Analysis Set (SAS)	1306	655
COMPLETED	1240	609
NOT COMPLETED	66	46

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 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Total of all reporting groups
Overall Participants	1306	655	1961
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	46 (13)	47 (12)	46 (13)
Sex: Female, Male (Count of Participants)
Female	955 73.1%	498 76%	1453 74.1%
Male	351 26.9%	157 24%	508 25.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	150 11.5%	86 13.1%	236 12%
Not Hispanic or Latino	1118 85.6%	551 84.1%	1669 85.1%
Unknown or Not Reported	38 2.9%	18 2.7%	56 2.9%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	17 1.3%	10 1.5%	27 1.4%
Asian	181 13.9%	80 12.2%	261 13.3%
Native Hawaiian or Other Pacific Islander	0 0%	2 0.3%	2 0.1%
Black or African American	72 5.5%	39 6%	111 5.7%
White	973 74.5%	499 76.2%	1472 75.1%
More than one race	25 1.9%	8 1.2%	33 1.7%
Unknown or Not Reported	38 2.9%	17 2.6%	55 2.8%

Outcome Measures

1. Primary Outcome

Title	Change in Body Weight (%)
Description	Change in body weight from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from both in-trial and on-treatment observation periods. In-trial observation period: the uninterrupted time interval from date of randomization (week 0) to date of last contact with trial site (week 75). On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68), including 2 weeks of follow-up. It excludes any period of temporary treatment interruption. Temporary treatment interruption is defined as more than 2 consecutive missed doses (off-treatment period).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Measure Participants	1306	655
In-trial observation period	-15.6 (10.1)	-2.8 (6.5)
On-treatment observation period	-16.9 (9.4)	-3.1 (6.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Semaglutide 2.4 mg, Placebo
	Comments	Treatment policy estimand
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-12.44
	Confidence Interval	(2-Sided) 95%; -13.37 to -11.51
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Semaglutide 2.4 mg, Placebo
	Comments	Hypothetical estimand
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-14.42
	Confidence Interval	(2-Sided) 95%; -15.29 to -13.55
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Participants Who Achieve 5 or More Percent Body Weight Reduction (Yes/no)
Description	Number of participants who achieved weight loss more than or equal to 5% (yes/no) at week 68 are 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 randomization (week 0) to last trial-related subject-site contact (week 75). On-treatment observation period: includes all time intervals in which participants are considered to be on treatment from the first (week 0) to last trial product administration (week 68), including 2 weeks of follow-up. It excludes any period of temporary treatment interruption.
Time Frame	After week 68

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Measure Participants	1306	655
Yes	1047 80.2%	182 27.8%
No	165 12.6%	395 60.3%
Yes	978 74.9%	165 25.2%
No	81 6.2%	334 51%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Semaglutide 2.4 mg, Placebo
	Comments	Treatment policy estimand
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	11.22
	Confidence Interval	(2-Sided) 95%; 8.88 to 14.19
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Semaglutide 2.4 mg, Placebo
	Comments	Hypothetical estimand
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	37.03
	Confidence Interval	(2-Sided) 95%; 28.02 to 48.95
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Subjects Who Achieve 10 or More Percent Body Weight Reduction (Yes/no)
Description	Number of participants who achieved weight loss more than or equal to (≥) 10% at 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 date of randomization (week 0) to date of last contact with trial site (week 75).
Time Frame	Week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomized 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 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Measure Participants	1212	577
Yes	838 64.2%	69 10.5%
No	374 28.6%	508 77.6%

4. Secondary Outcome

Title	Participants Who Achieve 15 or More Percent Body Weight Reduction (Yes/no)
Description	Number of participants who achieved more than or equal to (≥) 15% weight loss at 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 randomization (week 0) to last trial-related subject-site contact (week 75).
Time Frame	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 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Measure Participants	1212	577
Yes	612 46.9%	28 4.3%
No	600 45.9%	549 83.8%

5. Secondary Outcome

Title	Participants Who Achieve 20 or More Percent Body Weight Reduction (Yes/no)
Description	Number of participants who achieved more than or equal to (≥) 20% weight loss at 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 randomization (week 0) to last trial-related subject-site contact (week 75).
Time Frame	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 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Measure Participants	1212	577
Yes	388 29.7%	10 1.5%
No	824 63.1%	567 86.6%

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Measure Participants	1210	575
Mean (Standard Deviation) [Centimeter (cm)]	-14.1 (9.6)	-4.4 (6.9)

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Measure Participants	1210	574
Mean (Standard Deviation) [Millimeters of mercury (mmHg)]	-7 (14)	-1 (13)

8. Secondary Outcome

Title	Change in 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). In the metric of norm-based scores, 50 and 10 corresponds to the mean and standard deviation, respectively, for the 2009 US general population. Change from week 0 in the domain scores and component summary scores were evaluated at week 68. A positive change score indicates an improvement since baseline. These endpoints were evaluated based on the data from in-trial observation period which is the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Measure Participants	1195	566
Change in physical functioning score (SF-36)	2.3 (6.6)	0.4 (7.4)
Change in SF-36 (role-physical score)	1.1 (7.2)	-0.2 (7.2)
Change in SF-36 (bodily pain score)	0.5 (8.2)	-1.3 (8.9)
Change in SF-36 (general health score)	2.0 (7.2)	-0.6 (7.1)
Change in SF-36 (vitality score)	0.7 (8.0)	-1.3 (7.9)
Change in SF-36 (social functioning score)	-0.3 (6.6)	-1.4 (7.4)
Change in SF-36 (role-emotional score)	-0.9 (7.3)	-1.5 (7.6)
Change in SF-36 (mental health score)	-0.8 (7.0)	-1.7 (7.4)
Change in SF-36 (physical component summary)	2.4 (6.7)	0.2 (7.1)
Change in SF-36 (mental component summary)	-1.5 (7.1)	-2.1 (7.7)

9. Secondary Outcome

Title	Change in Impact of Weight on Quality of Life-Lite for Clinical Trial (IWQoL-Lite for CT) Score
Description	IWQoL-Lite for CT is a modified version of an instrument designed to assess weight-related quality of life. It is used to assess the impact of body weight changes on patients' physical and psychosocial functioning in three composite scores (physical function, physical and psychosocial) and a total score. The scores range between 0-100 where higher scores indicate a better quality of life. 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 randomization (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomized 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 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Measure Participants	1193	566
Change in physical function domain score	15.0 (21.6)	6.0 (21.1)
Change in physical domain score	14.0 (20.0)	5.0 (19.5)
Change in psychosocial domain score	17.4 (19.2)	6.9 (17.8)
Change in total score	16.2 (17.8)	6.3 (16.8)

10. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

FAS included all randomized 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 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Measure Participants	1212	577
Mean (Standard Deviation) [Kilogram (kg)]	-16.1 (10.6)	-2.9 (7.2)

11. Secondary Outcome

Title	Change in Body Mass Index (BMI) (kg/m2)
Description	Change in body mass index from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Measure Participants	1212	577
Mean (Standard Deviation) [Kilogram per square meter (kg/sqm)]	-5.8 (3.8)	-1.0 (2.5)

12. Secondary Outcome

Title	Change in HbA1C (%)
Description	Change in glycosylated haemoglobin (HbA1c) from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomized 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 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Measure Participants	1197	563
Mean (Standard Deviation) [Percentage point of HbA1c]	-0.5 (0.3)	-0.2 (0.3)

13. Secondary Outcome

Title	Change in HbA1C (mmol/Mol)
Description	Change in HbA1c from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

FAS included all randomized 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 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Measure Participants	1197	563
Mean (Standard Deviation) [millimoles per mole (mmol/mol)]	-5.1 (3.3)	-1.8 (3.0)

14. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

FAS included all randomized 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 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Measure Participants	1175	557
Mean (Standard Deviation) [milligrams per deciliter (mg/dL)]	-9.2 (10.9)	-0.4 (12.7)

15. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Measure Participants	1147	550
Geometric Mean (Geometric Coefficient of Variation) [Ratio of fasting serum insulin]	0.73 (62.3)	0.92 (56.5)

16. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

FAS included all randomized 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 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Measure Participants	1210	574
Mean (Standard Deviation) [Millimeters of mercury (mmHg)]	-3 (9)	-1 (9)

17. Secondary Outcome

Title	Change in Total Cholesterol (mg/dL) - Ratio to Baseline
Description	Change in fasting total cholesterol from baseline (week 0) to week 68 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 randomization (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Measure Participants	1196	561
Geometric Mean (Geometric Coefficient of Variation) [Ratio of total cholesterol]	0.96 (14.8)	1.00 (15.5)

18. Secondary Outcome

Title	Change in High-density Lipoproteins (HDL) (mg/dL) - Ratio to Baseline
Description	Change in fasting HDL from baseline (week 0) to week 68 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 randomization (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Measure Participants	1192	558
Geometric Mean (Geometric Coefficient of Variation) [Ratio of HDL cholesterol]	1.05 (16.1)	1.02 (14.9)

19. Secondary Outcome

Title	Change in Low-density Lipoproteins (LDL) (mg/dL) - Ratio to Baseline
Description	Change in fasting LDL from baseline (week 0) to week 68 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 randomization (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Measure Participants	1194	561
Geometric Mean (Geometric Coefficient of Variation) [Ratio of LDL cholesterol]	0.97 (23.7)	1.01 (25.5)

20. Secondary Outcome

Title	Change in Very Low-density Lipoproteins (VLDL) (mg/dL) - Ratio to Baseline
Description	Change in fasting VLDL from baseline (week 0) to week 68 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 randomization (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Measure Participants	1193	561
Geometric Mean (Geometric Coefficient of Variation) [Ratio of VLDL cholesterol]	0.77 (37.7)	0.92 (35.2)

21. Secondary Outcome

Title	Change in Free Fatty Acids (mg/dL) - Ratio to Baseline
Description	Change in fasting free fatty acids from baseline (week 0) to week 68 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 randomization (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Measure Participants	1154	552
Geometric Mean (Geometric Coefficient of Variation) [Ratio of free fatty acids]	0.83 (78.3)	0.93 (70.8)

22. Secondary Outcome

Title	Change in Triglycerides (mg/dL) - Ratio to Baseline
Description	Change in fasting triglycerides from baseline (week 0) to week 68 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 randomization (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Measure Participants	1194	561
Geometric Mean (Geometric Coefficient of Variation) [Ratio of triglycerides]	0.77 (38.3)	0.92 (36.2)

23. Secondary Outcome

Title	Change in High Sensitivity C-Reactive Protein (hsCRP) - (mg/L) - Ratio to Baseline
Description	Change in high sensitivity C-reactive protein from baseline (week 0) to week 68 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 randomization (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Measure Participants	1200	562
Geometric Mean (Geometric Coefficient of Variation) [Ratio of hsCRP]	0.45 (128.2)	0.84 (102.5)

24. Secondary Outcome

Title	Change in Plasminogen Activator Inhibitor-1 (PAI-1) Activity (AU/ml) - Ratio to Baseline
Description	Change in plasminogen activator inhibitor-1 activity from baseline (week 0) to week 68 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 randomization (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Measure Participants	1131	546
Geometric Mean (Geometric Coefficient of Variation) [Ratio of PAI-1]	1.15 (86.5)	1.53 (77.3)

25. Secondary Outcome

Title	Change in Soluble Leptin Receptor (ng/mL) - Ratio to Baseline
Description	Change in soluble leptin receptor from baseline (week 0) to week 68 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 randomization (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Measure Participants	1194	562
Geometric Mean (Geometric Coefficient of Variation) [Ratio of soluble leptin receptor]	1.07 (24.9)	1.02 (22.2)

26. Secondary Outcome

Title	Change in Leptin (ng/mL) - Ratio to Baseline
Description	Change in leptin from baseline (week 0) to week 68 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 randomization (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Measure Participants	1197	563
Geometric Mean (Geometric Coefficient of Variation) [Ratio of leptin]	0.52 (75.9)	0.87 (52.7)

27. Secondary Outcome

Title	Change in Body Composition (Total Fat Mass) (%)
Description	Change in body composition (total fat mass) from baseline (week 0) to week 68 is presented. Body composition was assessed using Dual Energy X-ray Absorpmetry (DEXA). The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

DEXA analysis set (DXA) includes participants in the sub-population of FAS that have had a DEXA scan performed at baseline. '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 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Measure Participants	83	39
Mean (Standard Deviation) [Percentage point]	-3.9 (5.4)	-0.3 (2.8)

28. Secondary Outcome

Title	Change in Body Composition (Total Fat Mass) (kg)
Description	Change in body composition (total fat mass) from baseline (week 0) to week 68 is presented. Body composition was assessed using Dual Energy X-ray Absorpmetry (DEXA). The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

DEXA analysis set (DXA) includes participants in the sub-population of FAS that have had a DEXA scan performed at baseline. '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 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Measure Participants	83	39
Mean (Standard Deviation) [Kilograms]	-9.3 (8.5)	-1.5 (5.1)

29. Secondary Outcome

Title	Change in Body Composition (Lean Body Mass) (%)
Description	Change in body composition (lean body mass) from baseline (week 0) to week 68 is presented. Body composition was assessed using DEXA. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

DEXA analysis set (DXA) includes participants in the sub-population of FAS that have had a DEXA scan performed at baseline. '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 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Measure Participants	83	39
Mean (Standard Deviation) [Percentage point]	3.4 (5.1)	0.2 (2.7)

30. Secondary Outcome

Title	Change in Body Composition (Lean Body Mass) (kg)
Description	Change in body composition (lean body mass) from baseline (week 0) to week 68 is presented. Body composition was assessed using DEXA. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

DEXA analysis set (DXA) includes participants in the sub-population of FAS that have had a DEXA scan performed at baseline. '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 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Measure Participants	83	39
Mean (Standard Deviation) [Kilograms]	-5.8 (4.6)	-1.8 (2.5)

31. Secondary Outcome

Title	Change in Body Composition (Visceral Fat Mass) (%)
Description	Change in body composition (visceral fat mass) from baseline (week 0) to week 68 is presented. Body composition was assessed using DEXA. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

DEXA analysis set (DXA) includes participants in the sub-population of FAS that have had a DEXA scan performed at baseline. '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 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Measure Participants	83	39
Mean (Standard Deviation) [Percentage point]	-2.2 (4.4)	-0.1 (4.5)

32. Secondary Outcome

Title	Change in Body Composition (Visceral Fat Mass) (kg)
Description	Change in body composition (visceral fat mass) from baseline (week 0) to week 68 is presented. Body composition was assessed using DEXA. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

DEXA analysis set (DXA) includes participants in the sub-population of FAS that have had a DEXA scan performed at baseline. '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 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Measure Participants	83	39
Mean (Standard Deviation) [Kilograms]	-0.4 (0.3)	-0.1 (0.3)

33. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

DEXA analysis set (DXA) includes participants in the sub-population of FAS that have had a DEXA scan performed at baseline. '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 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Measure Participants	89	42
Mean (Standard Deviation) [Percentage point]	-15.8 (11.1)	-3.4 (6.1)

34. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

DEXA analysis set (DXA) includes participants in the sub-population of FAS that have had a DEXA scan performed at baseline. '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 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Measure Participants	89	42
Mean (Standard Deviation) [Kilograms]	-15.5 (11.4)	-3.2 (6.1)

35. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

FAS included all randomized 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 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Measure Participants	1195	566
Yes (with threshold 4.3)	318 24.3%	97 14.8%
No (with threshold 4.3)	877 67.2%	469 71.6%
Yes (with threshold 3.7)	478 36.6%	153 23.4%
No (with threshold 3.7)	717 54.9%	413 63.1%

36. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

FAS included all randomized 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 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Measure Participants	1193	566
Yes (with threshold 20)	473 36.2%	145 22.1%
No (with threshold 20)	720 55.1%	421 64.3%
Yes (with threshold 14.6)	611 46.8%	186 28.4%
No (with threshold 14.6)	582 44.6%	380 58%

37. Secondary Outcome

Title	Number of Treatment Emergent Adverse Events (TEAEs)
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 for which the onset of the event occurs in the on-treatment 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	Baseline (week 0) to week 75

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Measure Participants	1306	655
Number [Events]	9658	3302

38. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Measure Participants	1306	655
Number [Events]	164	53

39. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Measure Participants	1059	499
Mean (Standard Deviation) [beats per minute (bpm)]	3 (10)	-1 (10)

40. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Measure Participants	1053	497
Geometric Mean (Geometric Coefficient of Variation) [Ratio of amylase]	1.14 (21.6)	1.03 (21.4)

41. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Measure Participants	1053	496
Geometric Mean (Geometric Coefficient of Variation) [Ratio of lipase]	1.41 (49.3)	0.97 (37.3)

42. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Measure Participants	1050	497
Geometric Mean (Geometric Coefficient of Variation) [Ratio of calcitonin]	0.99 (37.6)	0.95 (40.9)

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 randomized treatment and no later than the date of last dose + 7 weeks.
Arm/Group Title	Sema 2.4 mg		Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.		Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
All Cause Mortality
	Sema 2.4 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/1306 (0.1%)		1/655 (0.2%)
Serious Adverse Events
	Sema 2.4 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	128/1306 (9.8%)		42/655 (6.4%)
Blood and lymphatic system disorders
Anaemia	2/1306 (0.2%)	2	0/655 (0%)	0
Splenic haemorrhage	1/1306 (0.1%)	1	0/655 (0%)	0
Cardiac disorders
Acute myocardial infarction	2/1306 (0.2%)	2	1/655 (0.2%)	1
Angina pectoris	0/1306 (0%)	0	1/655 (0.2%)	1
Angina unstable	1/1306 (0.1%)	1	0/655 (0%)	0
Atrial fibrillation	2/1306 (0.2%)	4	1/655 (0.2%)	1
Atrial tachycardia	1/1306 (0.1%)	1	0/655 (0%)	0
Cardiomyopathy	0/1306 (0%)	0	1/655 (0.2%)	1
Coronary artery stenosis	1/1306 (0.1%)	1	0/655 (0%)	0
Myocardial infarction	0/1306 (0%)	0	2/655 (0.3%)	2
Myocarditis	0/1306 (0%)	0	1/655 (0.2%)	1
Palpitations	1/1306 (0.1%)	1	0/655 (0%)	0
Ear and labyrinth disorders
Meniere's disease	1/1306 (0.1%)	1	0/655 (0%)	0
Vertigo	3/1306 (0.2%)	3	0/655 (0%)	0
Eye disorders
Diplopia	1/1306 (0.1%)	2	0/655 (0%)	0
Optic ischaemic neuropathy	2/1306 (0.2%)	2	0/655 (0%)	0
Gastrointestinal disorders
Abdominal hernia	1/1306 (0.1%)	1	0/655 (0%)	0
Abdominal pain	3/1306 (0.2%)	3	0/655 (0%)	0
Abdominal pain lower	1/1306 (0.1%)	1	0/655 (0%)	0
Anal fistula	1/1306 (0.1%)	1	0/655 (0%)	0
Colitis	2/1306 (0.2%)	2	0/655 (0%)	0
Colitis ischaemic	1/1306 (0.1%)	1	0/655 (0%)	0
Constipation	1/1306 (0.1%)	1	0/655 (0%)	0
Diarrhoea	1/1306 (0.1%)	1	0/655 (0%)	0
Duodenal ulcer	1/1306 (0.1%)	1	0/655 (0%)	0
Enteritis	1/1306 (0.1%)	1	0/655 (0%)	0
Hiatus hernia	2/1306 (0.2%)	2	0/655 (0%)	0
Large intestine perforation	1/1306 (0.1%)	1	0/655 (0%)	0
Nausea	1/1306 (0.1%)	1	0/655 (0%)	0
Oesophageal achalasia	1/1306 (0.1%)	1	0/655 (0%)	0
Pancreatitis acute	2/1306 (0.2%)	2	0/655 (0%)	0
Volvulus	1/1306 (0.1%)	1	0/655 (0%)	0
Vomiting	4/1306 (0.3%)	4	0/655 (0%)	0
General disorders
Chest pain	1/1306 (0.1%)	1	0/655 (0%)	0
Non-cardiac chest pain	2/1306 (0.2%)	2	0/655 (0%)	0
Pyrexia	1/1306 (0.1%)	1	0/655 (0%)	0
Vascular stent occlusion	1/1306 (0.1%)	1	0/655 (0%)	0
Hepatobiliary disorders
Bile duct stone	1/1306 (0.1%)	1	0/655 (0%)	0
Cholecystitis	4/1306 (0.3%)	4	0/655 (0%)	0
Cholecystitis acute	3/1306 (0.2%)	3	0/655 (0%)	0
Cholelithiasis	12/1306 (0.9%)	12	1/655 (0.2%)	1
Hypertransaminasaemia	1/1306 (0.1%)	1	0/655 (0%)	0
Immune system disorders
Hypersensitivity	0/1306 (0%)	0	1/655 (0.2%)	1
Infections and infestations
Acute sinusitis	1/1306 (0.1%)	1	0/655 (0%)	0
Appendicitis	5/1306 (0.4%)	5	1/655 (0.2%)	1
Appendicitis perforated	1/1306 (0.1%)	1	0/655 (0%)	0
Arthritis infective	0/1306 (0%)	0	1/655 (0.2%)	1
Bacterial colitis	1/1306 (0.1%)	1	0/655 (0%)	0
Cellulitis	1/1306 (0.1%)	1	0/655 (0%)	0
Chronic sinusitis	1/1306 (0.1%)	1	0/655 (0%)	0
Cytomegalovirus infection	1/1306 (0.1%)	1	0/655 (0%)	0
Device related infection	1/1306 (0.1%)	1	0/655 (0%)	0
Empyema	0/1306 (0%)	0	1/655 (0.2%)	1
Gastroenteritis	5/1306 (0.4%)	5	0/655 (0%)	0
Gastroenteritis astroviral	1/1306 (0.1%)	1	0/655 (0%)	0
Hepatitis E	1/1306 (0.1%)	1	0/655 (0%)	0
Large intestine infection	1/1306 (0.1%)	1	0/655 (0%)	0
Meningitis viral	0/1306 (0%)	0	1/655 (0.2%)	1
Neutropenic sepsis	0/1306 (0%)	0	1/655 (0.2%)	1
Pneumonia	0/1306 (0%)	0	2/655 (0.3%)	2
Pyelonephritis	2/1306 (0.2%)	2	0/655 (0%)	0
Respiratory syncytial virus infection	1/1306 (0.1%)	1	0/655 (0%)	0
Respiratory tract infection	0/1306 (0%)	0	1/655 (0.2%)	1
Septic shock	0/1306 (0%)	0	1/655 (0.2%)	1
Sinusitis	1/1306 (0.1%)	1	0/655 (0%)	0
Staphylococcal infection	1/1306 (0.1%)	1	0/655 (0%)	0
Staphylococcal sepsis	0/1306 (0%)	0	1/655 (0.2%)	1
Subcutaneous abscess	1/1306 (0.1%)	1	0/655 (0%)	0
Tonsillitis	1/1306 (0.1%)	1	0/655 (0%)	0
Toxoplasmosis	0/1306 (0%)	0	1/655 (0.2%)	1
Urinary tract infection	0/1306 (0%)	0	1/655 (0.2%)	1
Injury, poisoning and procedural complications
Ankle fracture	1/1306 (0.1%)	1	1/655 (0.2%)	1
Femur fracture	1/1306 (0.1%)	2	0/655 (0%)	0
Gun shot wound	0/1306 (0%)	0	1/655 (0.2%)	1
Ligament rupture	1/1306 (0.1%)	1	0/655 (0%)	0
Meniscus injury	1/1306 (0.1%)	1	1/655 (0.2%)	1
Post procedural haemorrhage	1/1306 (0.1%)	1	0/655 (0%)	0
Procedural haemorrhage	1/1306 (0.1%)	1	0/655 (0%)	0
Radius fracture	1/1306 (0.1%)	1	0/655 (0%)	0
Rib fracture	1/1306 (0.1%)	1	0/655 (0%)	0
Road traffic accident	1/1306 (0.1%)	1	0/655 (0%)	0
Subdural haematoma	1/1306 (0.1%)	1	0/655 (0%)	0
Thoracic vertebral fracture	1/1306 (0.1%)	1	0/655 (0%)	0
Tibia fracture	1/1306 (0.1%)	1	0/655 (0%)	0
Investigations
Lipase increased	1/1306 (0.1%)	1	0/655 (0%)	0
Weight increased	0/1306 (0%)	0	1/655 (0.2%)	1
Metabolism and nutrition disorders
Gout	1/1306 (0.1%)	1	0/655 (0%)	0
Hypokalaemia	1/1306 (0.1%)	1	0/655 (0%)	0
Musculoskeletal and connective tissue disorders
Arthropathy	0/1306 (0%)	0	1/655 (0.2%)	1
Back pain	1/1306 (0.1%)	1	1/655 (0.2%)	1
Costochondritis	1/1306 (0.1%)	1	0/655 (0%)	0
Intervertebral disc degeneration	1/1306 (0.1%)	1	0/655 (0%)	0
Intervertebral disc protrusion	1/1306 (0.1%)	1	1/655 (0.2%)	1
Muscular weakness	1/1306 (0.1%)	1	0/655 (0%)	0
Musculoskeletal chest pain	0/1306 (0%)	0	1/655 (0.2%)	1
Musculoskeletal pain	1/1306 (0.1%)	1	0/655 (0%)	0
Myalgia intercostal	1/1306 (0.1%)	1	0/655 (0%)	0
Osteoarthritis	3/1306 (0.2%)	3	2/655 (0.3%)	2
Rotator cuff syndrome	1/1306 (0.1%)	1	0/655 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cervix carcinoma stage 0	1/1306 (0.1%)	1	0/655 (0%)	0
Gastrointestinal stromal tumour	1/1306 (0.1%)	1	0/655 (0%)	0
Glioblastoma	0/1306 (0%)	0	1/655 (0.2%)	1
Hairy cell leukaemia	0/1306 (0%)	0	1/655 (0.2%)	1
Intraductal proliferative breast lesion	2/1306 (0.2%)	2	1/655 (0.2%)	1
Invasive ductal breast carcinoma	1/1306 (0.1%)	1	0/655 (0%)	0
Leiomyoma	1/1306 (0.1%)	1	0/655 (0%)	0
Ovarian adenoma	1/1306 (0.1%)	1	0/655 (0%)	0
Papillary thyroid cancer	1/1306 (0.1%)	1	0/655 (0%)	0
Prostate cancer	1/1306 (0.1%)	1	0/655 (0%)	0
Nervous system disorders
Aphasia	1/1306 (0.1%)	1	0/655 (0%)	0
Cerebral infarction	1/1306 (0.1%)	1	0/655 (0%)	0
Cranial nerve disorder	1/1306 (0.1%)	1	0/655 (0%)	0
Dizziness	1/1306 (0.1%)	1	0/655 (0%)	0
Headache	1/1306 (0.1%)	1	0/655 (0%)	0
Idiopathic intracranial hypertension	1/1306 (0.1%)	1	0/655 (0%)	0
Ischaemic stroke	0/1306 (0%)	0	1/655 (0.2%)	1
Nerve compression	1/1306 (0.1%)	1	1/655 (0.2%)	1
Peroneal nerve palsy	0/1306 (0%)	0	1/655 (0.2%)	1
Psychogenic seizure	0/1306 (0%)	0	1/655 (0.2%)	1
Vertigo CNS origin	1/1306 (0.1%)	1	0/655 (0%)	0
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	2/1306 (0.2%)	2	0/655 (0%)	0
Ectopic pregnancy	1/1306 (0.1%)	1	0/655 (0%)	0
Psychiatric disorders
Acute stress disorder	1/1306 (0.1%)	1	0/655 (0%)	0
Anxiety	1/1306 (0.1%)	1	0/655 (0%)	0
Suicidal ideation	1/1306 (0.1%)	1	0/655 (0%)	0
Suicide attempt	0/1306 (0%)	0	1/655 (0.2%)	1
Renal and urinary disorders
Calculus urinary	1/1306 (0.1%)	1	0/655 (0%)	0
Nephrolithiasis	1/1306 (0.1%)	1	0/655 (0%)	0
Reproductive system and breast disorders
Dysfunctional uterine bleeding	1/1306 (0.1%)	1	0/655 (0%)	0
Erectile dysfunction	0/1306 (0%)	0	1/655 (0.2%)	1
Ovarian cyst	1/1306 (0.1%)	1	0/655 (0%)	0
Uterine haemorrhage	1/1306 (0.1%)	1	0/655 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	0/1306 (0%)	0	1/655 (0.2%)	1
Asthma	0/1306 (0%)	0	2/655 (0.3%)	2
Nasal polyps	1/1306 (0.1%)	1	0/655 (0%)	0
Pleurisy	0/1306 (0%)	0	1/655 (0.2%)	1
Pulmonary embolism	2/1306 (0.2%)	2	2/655 (0.3%)	2
Tonsillar hypertrophy	1/1306 (0.1%)	1	0/655 (0%)	0
Skin and subcutaneous tissue disorders
Actinic keratosis	1/1306 (0.1%)	1	0/655 (0%)	0
Decubitus ulcer	1/1306 (0.1%)	1	0/655 (0%)	0
Hidradenitis	1/1306 (0.1%)	1	0/655 (0%)	0
Surgical and medical procedures
Abdominoplasty	0/1306 (0%)	0	1/655 (0.2%)	1
Bone prosthesis insertion	0/1306 (0%)	0	1/655 (0.2%)	1
Cholecystectomy	1/1306 (0.1%)	1	1/655 (0.2%)	1
Gastric bypass	1/1306 (0.1%)	1	1/655 (0.2%)	1
Hip surgery	0/1306 (0%)	0	1/655 (0.2%)	1
Intervertebral disc operation	1/1306 (0.1%)	1	0/655 (0%)	0
Vascular disorders
Deep vein thrombosis	0/1306 (0%)	0	1/655 (0.2%)	1
Haematoma	0/1306 (0%)	0	1/655 (0.2%)	1
Other (Not Including Serious) Adverse Events
	Sema 2.4 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1052/1306 (80.6%)		447/655 (68.2%)
Gastrointestinal disorders
Abdominal distension	96/1306 (7.4%)	135	31/655 (4.7%)	42
Abdominal pain	127/1306 (9.7%)	172	36/655 (5.5%)	41
Abdominal pain upper	125/1306 (9.6%)	176	35/655 (5.3%)	37
Constipation	305/1306 (23.4%)	389	62/655 (9.5%)	73
Diarrhoea	411/1306 (31.5%)	765	104/655 (15.9%)	138
Dyspepsia	135/1306 (10.3%)	179	23/655 (3.5%)	30
Eructation	112/1306 (8.6%)	139	3/655 (0.5%)	3
Gastrooesophageal reflux disease	82/1306 (6.3%)	92	20/655 (3.1%)	21
Nausea	576/1306 (44.1%)	1067	114/655 (17.4%)	146
Vomiting	321/1306 (24.6%)	632	43/655 (6.6%)	52
General disorders
Fatigue	104/1306 (8%)	120	28/655 (4.3%)	29
Infections and infestations
Gastroenteritis	81/1306 (6.2%)	99	30/655 (4.6%)	38
Influenza	89/1306 (6.8%)	112	63/655 (9.6%)	79
Nasopharyngitis	281/1306 (21.5%)	480	133/655 (20.3%)	216
Sinusitis	70/1306 (5.4%)	83	36/655 (5.5%)	40
Upper respiratory tract infection	114/1306 (8.7%)	158	80/655 (12.2%)	116
Urinary tract infection	68/1306 (5.2%)	83	28/655 (4.3%)	33
Metabolism and nutrition disorders
Decreased appetite	124/1306 (9.5%)	139	22/655 (3.4%)	26
Musculoskeletal and connective tissue disorders
Arthralgia	81/1306 (6.2%)	92	43/655 (6.6%)	47
Back pain	106/1306 (8.1%)	120	53/655 (8.1%)	55
Nervous system disorders
Dizziness	98/1306 (7.5%)	129	23/655 (3.5%)	35
Headache	198/1306 (15.2%)	386	80/655 (12.2%)	104
Respiratory, thoracic and mediastinal disorders
Cough	40/1306 (3.1%)	45	33/655 (5%)	35

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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