STEP 5: Two-year 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

NCT03693430

Collaborator

(none)

304

Enrollment

Locations

Arms

29.6

Actual Duration (Months)

7.4

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will look at the change in body weight from the start to the end of the study. Researchers will compare the weight loss in people taking semaglutide (a new medicine) to people taking "dummy" medicine. In addition to taking the medicine, participants will also have talks with study staff about healthy food choices, how the participant can be more physically active and what participants can do to lose weight. Participants will either get semaglutide or "dummy" medicine - which treatment the participant gets 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 will last for about 2 years. The participants will have 19 clinic visits and 15 phone calls with the study doctor.

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

Study Design

Study Type:

Interventional

Actual Enrollment :

304 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Two-year Effect and Safety of Semaglutide 2.4 mg Once-weekly in Subjects With Overweight or Obesity

Actual Study Start Date :

Oct 5, 2018

Actual Primary Completion Date :

Jan 29, 2021

Actual Study Completion Date :

Mar 23, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Semaglutide Participants will receive semaglutide 2.4 mg during 104-week treatment period in addition to a reduced-calorie diet and increased physical activity.	Drug: Semaglutide Subcutaneous (s.c., under the skin) injections of semaglutide once weekly at escalating doses (0.25 mg/week, 0.5 mg/week, 1.0 mg/week, 1.7 mg/week, 2.4 mg/week). The dose will be escalated to next level every 4 weeks
Placebo Comparator: Placebo Participants will receive placebo (semaglutide) during 104-week treatment period in addition to a reduced-calorie diet and increased physical activity.	Drug: Placebo (Semaglutide) S.c. injections of placebo once weekly at a similar dose escalation manner as semaglutide (placebo matched to semaglutide 0.25 mg/week, 0.5 mg/week, 1.0 mg/week, 1.7 mg/week, 2.4 mg/week). The dose will be escalated to next level every 4 weeks

Arm

Intervention/Treatment

Experimental: Semaglutide

Participants will receive semaglutide 2.4 mg during 104-week treatment period in addition to a reduced-calorie diet and increased physical activity.

Drug: Semaglutide

Subcutaneous (s.c., under the skin) injections of semaglutide once weekly at escalating doses (0.25 mg/week, 0.5 mg/week, 1.0 mg/week, 1.7 mg/week, 2.4 mg/week). The dose will be escalated to next level every 4 weeks

Placebo Comparator: Placebo

Participants will receive placebo (semaglutide) during 104-week treatment period in addition to a reduced-calorie diet and increased physical activity.

Drug: Placebo (Semaglutide)

S.c. injections of placebo once weekly at a similar dose escalation manner as semaglutide (placebo matched to semaglutide 0.25 mg/week, 0.5 mg/week, 1.0 mg/week, 1.7 mg/week, 2.4 mg/week). The dose will be escalated to next level every 4 weeks

Outcome Measures

Primary Outcome Measures

Percentage Change From Baseline (Week 0) to Week 104 in Body Weight [From Baseline (Week 0) to Week 104]
Percentage change in body weight for both in-trial and on-treatment observation period from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from both in-trial and on-treatment periods. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site. On-treatment observation period: the interval from first to last trial product administration plus 2 weeks of follow-up and excluding any period of temporary treatment interruption defined as >2 consecutive missed doses (corresponding to >2 weeks off-treatment).
Number of Participants Who Achieved (Yes/no): Body Weight Reduction More Than or Equal to 5% [At Week 104]
Number of participants who achieved greater than or equal to (>=) 5% weight loss at 104 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved >=5% weight loss, whereas 'No' infers the number of participants who have not achieved >=5% weight loss. The outcome measure was evaluated based on the data from both in-trial and on-treatment periods. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site. On-treatment observation period: the interval from first to last trial product administration plus 2 weeks of follow-up and excluding any period of temporary treatment interruption defined as >2 consecutive missed doses (corresponding to >2 weeks off-treatment).

Secondary Outcome Measures

Number of Participants Who Achieved (Yes/no): Body Weight Reduction More Than or Equal to 10% [At Week 104]
Number of participants who achieved >=10% weight loss at 104 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved >=10% weight loss, whereas 'No' infers the number of participants who have not achieved >=10% weight loss. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Number of Participants Who Achieved (Yes/no): Body Weight Reduction More Than or Equal to 15% [At Week 104]
Number of participants who achieved >=15% weight loss at 104 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved >=15% weight loss, whereas 'No' infers the number of participants who have not achieved >=15% weight loss. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Number of Participants Who Achieved (Yes/no): Body Weight Reduction More Than or Equal to 20% [At Week 104]
Number of participants who achieved >=20% weight loss at 104 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved >=20% weight loss, whereas 'No' infers the number of participants who have not achieved >=20% weight loss. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Change From Baseline (Week 0) to Week 104 in Waist Circumference [From Baseline (Week 0) to Week 104]
Change in waist circumference from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Change From Baseline (Week 0) to Week 104 in Body Weight (kg) [From Baseline (Week 0) to Week 104]
Change in body weight from baseline (week 0) to week 104 in kilogram (kg) is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Change From Baseline (Week 0) to Week 104 in Body Mass Index (BMI) [From Baseline (Week 0) to Week 104]
Change in BMI from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Change From Baseline (Week 0) to Week 104 in Systolic Blood Pressure [From Baseline (Week 0) to Week 104]
Change in systolic blood pressure from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Change From Baseline (Week 0) to Week 104 in Diastolic Blood Pressure [From Baseline (Week 0) to Week 104]
Change in diastolic blood pressure from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Change in Total Cholesterol-ratio to Baseline [From Baseline (Week 0) to Week 104]
Change in total cholesterol from baseline (week 0) to week 104 measured in milligrams per deciliter (mg/dL) is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Change in High Density Lipoprotein (HDL) Cholesterol-ratio to Baseline [From Baseline (Week 0) to Week 104]
Change in HDL cholesterol from baseline (week 0) to week 104 measured in mg/dL is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Change in Low Density Lipoprotein (LDL) Cholesterol-ratio to Baseline [From Baseline (Week 0) to Week 104]
Change in LDL cholesterol from baseline (week 0) to week 104 measured in mg/dL is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Change in Very Low Density Lipoprotein (VLDL) Cholesterol-ratio to Baseline [From Baseline (Week 0) to Week 104]
Change in VLDL cholesterol from baseline (week 0) to week 104 measured in mg/dL is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Change in Free Fatty Acids-ratio to Baseline [From Baseline (Week 0) to Week 104]
Change in free fatty acids from baseline (week 0) to week 104 measured in mg/dL is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Change in Triglycerides-ratio to Baseline [From Baseline (Week 0) to Week 104]
Change in triglycerides from baseline (week 0) to week 104 measured in mg/dL is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Change in High Sensitivity C-reactive Protein (hsCRP)-Ratio to Baseline [From Baseline (Week 0) to Week 104]
Change in hsCRP from baseline (week 0) to week 104 measured in mg/dL is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Change in Glycated Haemoglobin (HbA1c) (Percent [%]) [From Baseline (Week 0) to Week 104]
Change in HbA1c from baseline (week 0) to week 104 in % is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Change From Baseline (Week 0) to Week 104 in HbA1c (mmol/Mol) [From Baseline (Week 0) to Week 104]
Change in HbA1c from baseline (week 0) to week 104 in millimole per mole (mmol/mol) is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Change From Baseline (Week 0) to Week 104 in Fasting Plasma Glucose (FPG) (mmol/L) [From Baseline (Week 0) to Week 104]
Change in FPG from baseline (week 0) to week 104 in millimoles per liter (mmol/L) is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Change From Baseline (Week 0) to Week 104 in FPG (mg/dL) [From Baseline (Week 0) to Week 104]
Change in FPG from baseline (week 0) to week 104 in mg/dL is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Change in Fasting Serum Insulin-ratio to Baseline (Pmol/L) [From Baseline (Week 0) to Week 104]
Change in fasting serum insulin from baseline (week 0) to week 104 measured in picomole per liter (pmol) is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Change in Fasting Serum Insulin-ratio to Baseline (mIU/mL) [From Baseline (Week 0) to Week 104]
Change in fasting serum insulin from baseline (week 0) to week 104 measured in milli-international units per milliliter (mIU/mL) is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Percentage Change From Baseline (Week 0) to Week 52 in Body Weight [From Baseline (Week 0) to Week 52]
Percentage change in body weight from baseline (week 0) to week 52 is presented.
Change From Baseline (Week 0) to Week 52 in Body Weight (kg) [From Baseline (Week 0) to Week 52]
Change in body weight from baseline (week 0) to week 52 in kg is presented.
Change From Baseline (Week 0) to Week 52 in Body Mass Index (BMI) [From Baseline (Week 0) to Week 52]
Change in BMI from baseline (week 0) to week 52 is presented.
Change From Baseline (Week 0) to Week 52 in Waist Circumference [From Baseline (Week 0) to Week 52]
Change in waist circumference from baseline (week 0) to week 52 is presented.
Number of Participants Who at 52 Weeks Achieved (Yes/no): Body Weight Reduction More Than or Equal to 5% [At Week 52]
Number of participants who achieved >=5% weight loss at 52 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved >=5% weight loss, whereas 'No' infers the number of participants who have not achieved >=5% weight loss.
Number of Participants Who at 52 Weeks Achieved (Yes/no): Body Weight Reduction More Than or Equal to 10% [At Week 52]
Number of participants who achieved >=10% weight loss at 52 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved >=10% weight loss, whereas 'No' infers the number of participants who have not achieved >=10% weight loss.
Number of Participants Who at 52 Weeks Achieved (Yes/no): Body Weight Reduction More Than or Equal to 15% [At Week 52]
Number of participants who achieved >=15% weight loss at 52 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved >=15% weight loss, whereas 'No' infers the number of participants who have not achieved >=15% weight loss.
Number of Participants Who at 52 Weeks Achieved (Yes/no): Body Weight Reduction More Than or Equal to 20% [At Week 52]
Number of participants who achieved >=20% weight loss at 52 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved >=20% weight loss, whereas 'No' infers the number of participants who have not achieved >=20% weight loss.
Number of Treatment-emergent Adverse Events (TEAEs) [From Baseline (Week 0) to Week 111]
An adverse event (AE) was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to treatment. The outcome measure was evaluated based on the data from on-treatment observation period, which was defined as the interval from first to last trial product administration plus 7 weeks of follow-up and excluding any period of temporary treatment interruption defined as >7 consecutive missed doses (corresponding to >7 weeks off-treatment).
Number of Serious Adverse Events (SAEs) [From Baseline (Week 0) to Week 111]
A SAE was 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 111 is presented. The outcome measure was evaluated based on the data from on-treatment observation period, which was defined as the interval from first to last trial product administration plus 7 weeks of follow-up and excluding any period of temporary treatment interruption defined as >7 consecutive missed doses (corresponding to >7 weeks off-treatment).
Change From Baseline (Week 0) to Week 104 in Pulse [From Baseline (Week 0) to Week 104]
Change in pulse from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from on-treatment observation period, which was defined as the interval from first to last trial product administration plus 2 weeks of follow-up and excluding any period of temporary treatment interruption defined as >2 consecutive missed doses (corresponding to >2 weeks off-treatment).
Change From Baseline (Week 0) to Week 104 in Amylase [From Baseline (Week 0) to Week 104]
Change in amylase from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from on-treatment observation period, which was defined as the interval from first to last trial product administration plus 2 weeks of follow-up and excluding any period of temporary treatment interruption defined as >2 consecutive missed doses (corresponding to >2 weeks off-treatment).
Change From Baseline (Week 0) to Week 104 in Lipase [From Baseline (Week 0) to Week 104]
Change in lipase from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from on-treatment observation period, which was defined as the interval from first to last trial product administration plus 2 weeks of follow-up and excluding any period of temporary treatment interruption defined as >2 consecutive missed doses (corresponding to >2 weeks off-treatment).
Change From Baseline (Week 0) to Week 104 in Calcitonin [From Baseline (Week 0) to Week 104]
Change in calcitonin from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from on-treatment observation period, which was defined as the interval from first to last trial product administration plus 2 weeks of follow-up and excluding any period of temporary treatment interruption defined as >2 consecutive missed doses (corresponding to >2 weeks off-treatment).

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or female, age more than or equal to 18 years at the time of signing informed consent
Body mass index (BMI) more than or equal to 30 kg/m^{2 or more than or equal to 27
kg/m}2 with the presence of at least one of the following weight-related comorbidities (treated or untreated): hypertension, dyslipidaemia, obstructive sleep apnoea or cardiovascular disease
History of at least one self-reported unsuccessful dietary effort to lose body weight

Exclusion criteria:

HbA1c more than or equal to 48 mmol/mol (6.5%) as measured by the central laboratory at screening
A self-reported change in body weight more than 5 kg (11 lbs) within 90 days before screening irrespective of medical records

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Birmingham	Alabama	United States	35294
2	Novo Nordisk Investigational Site	Los Angeles	California	United States	90057
3	Novo Nordisk Investigational Site	Aurora	Colorado	United States	80045
4	Novo Nordisk Investigational Site	Golden	Colorado	United States	80401
5	Novo Nordisk Investigational Site	Waterbury	Connecticut	United States	06708
6	Novo Nordisk Investigational Site	Jacksonville	Florida	United States	32205
7	Novo Nordisk Investigational Site	Ocala	Florida	United States	34471
8	Novo Nordisk Investigational Site	Saint Peters	Missouri	United States	63303
9	Novo Nordisk Investigational Site	Butte	Montana	United States	59701
10	Novo Nordisk Investigational Site	Albany	New York	United States	12203
11	Novo Nordisk Investigational Site	Rochester	New York	United States	14609
12	Novo Nordisk Investigational Site	Kingsport	Tennessee	United States	37660
13	Novo Nordisk Investigational Site	Austin	Texas	United States	78731
14	Novo Nordisk Investigational Site	Round Rock	Texas	United States	78681
15	Novo Nordisk Investigational Site	Arlington	Virginia	United States	22206
16	Novo Nordisk Investigational Site	Surrey	British Columbia	Canada	V3Z 2N6
17	Novo Nordisk Investigational Site	Moncton	New Brunswick	Canada	E1G 1A7
18	Novo Nordisk Investigational Site	Halifax	Nova Scotia	Canada	B3H 1V7
19	Novo Nordisk Investigational Site	Hamilton	Ontario	Canada	L8L 5G8
20	Novo Nordisk Investigational Site	Hamilton	Ontario	Canada	L8M 1K7
21	Novo Nordisk Investigational Site	Toronto	Ontario	Canada	M4G 3E8
22	Novo Nordisk Investigational Site	Toronto	Ontario	Canada	M4P 1P2
23	Novo Nordisk Investigational Site	Montreal	Quebec	Canada	H4N 2W2
24	Novo Nordisk Investigational Site	Quebec		Canada	G1V 4G2
25	Novo Nordisk Investigational Site	Budapest		Hungary	1132
26	Novo Nordisk Investigational Site	Budapest		Hungary	1152
27	Novo Nordisk Investigational Site	Budapest		Hungary	H-1134
28	Novo Nordisk Investigational Site	Debrecen		Hungary	4043
29	Novo Nordisk Investigational Site	Komarom		Hungary	2900
30	Novo Nordisk Investigational Site	Szekszárd		Hungary	7100
31	Novo Nordisk Investigational Site	Bologna		Italy	40138
32	Novo Nordisk Investigational Site	Palermo		Italy	90127
33	Novo Nordisk Investigational Site	Pisa		Italy	56124
34	Novo Nordisk Investigational Site	Rome		Italy	00168
35	Novo Nordisk Investigational Site	Siena		Italy	53100
36	Novo Nordisk Investigational Site	Alcorcón		Spain	28922
37	Novo Nordisk Investigational Site	Almeria		Spain	04009
38	Novo Nordisk Investigational Site	Hospitalet de Llobregat		Spain	08907
39	Novo Nordisk Investigational Site	Pamplona		Spain	31008
40	Novo Nordisk Investigational Site	Pozuelo de Alarcon		Spain	28223
41	Novo Nordisk Investigational Site	Sevilla		Spain	41010

Sponsors and Collaborators

Novo Nordisk A/S

Investigators

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

Study Documents (Full-Text)

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:

NCT03693430

Other Study ID Numbers:

NN9536-4378
2017-003726-32
U1111-1202-1740

First Posted:

Oct 3, 2018

Last Update Posted:

Mar 23, 2022

Last Verified:

Mar 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Obesity

Overweight

Study Results

Participant Flow

Recruitment Details	The trial was conducted at 41 sites in 5 countries as follows: Canada (9 sites), Hungary (6 sites), Italy (5 sites), Spain (6 sites), and United States (15 sites).
Pre-assignment Detail	Participants were randomized in a 1:1 manner to receive treatment with semaglutide 2.4 milligram (mg) or placebo once weekly as an adjunct to a reduced-calorie diet and increased physical activity. The trial has a 104 weeks treatment period (16 weeks of dose escalation period and 88 weeks of maintenance dose).

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly subcutaneous (s.c) injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Period Title: Overall Study
STARTED	152	152
Full Analysis Set (FAS)	152	152
Safety Analysis Set (SAS)	152	152
COMPLETED	148	134
NOT COMPLETED	4	18

Baseline Characteristics

Arm/Group Title	Semaglutide 2.4 mg	Placebo	Total
Arm/Group Description	Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.	Total of all reporting groups
Overall Participants	152	152	304
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47 (12)	47 (10)	47 (11)
Sex: Female, Male (Count of Participants)
Female	123 80.9%	113 74.3%	236 77.6%
Male	29 19.1%	39 25.7%	68 22.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	18 11.8%	21 13.8%	39 12.8%
Not Hispanic or Latino	134 88.2%	131 86.2%	265 87.2%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
White	141 92.8%	142 93.4%	283 93.1%
Black or African American	7 4.6%	5 3.3%	12 3.9%
Other	0 0%	4 2.6%	4 1.3%
American Indian or Alaska Native	2 1.3%	1 0.7%	3 1%
Asian	2 1.3%	0 0%	2 0.7%

Outcome Measures

1. Primary Outcome

Title	Percentage Change From Baseline (Week 0) to Week 104 in Body Weight
Description	Percentage change in body weight for both in-trial and on-treatment observation period from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from both in-trial and on-treatment periods. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site. On-treatment observation period: the interval from first to last trial product administration plus 2 weeks of follow-up and excluding any period of temporary treatment interruption defined as >2 consecutive missed doses (corresponding to >2 weeks off-treatment).
Time Frame	From Baseline (Week 0) to Week 104

Outcome Measure Data

Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure and Number Analyzed = participants with available data for each specified category.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Measure Participants	144	128
In-trial observation period	-15.9 (12.3)	-1.9 (8.9)
On-treatment observation period	-17.3 (11.9)	-2.0 (8.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Semaglutide 2.4 mg, Placebo
	Comments	Treatment policy estimand
	Type of Statistical Test	Superiority
	Comments	Week 104 responses were analysed using an analysis of covariance model with randomised treatment as factor and baseline body weight as covariate. Missing observations were multiple (x1000) imputed from retrieved subjects of the same randomised treatment arm.

Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-12.55
	Confidence Interval	(2-Sided) 95% -15.33 to -9.77
	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	All responses prior to first discontinuation of treatment (or initiation of other anti-obesity medication or bariatric surgery) were included in a mixed model for repeated measurements with randomised treatment as factor and baseline body weight as covariate, all nested within visit.

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	MMRM (Mixed model repeated measurement)
	Comments

Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-16.05
	Confidence Interval	(2-Sided) 95% -18.64 to -13.45
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Number of Participants Who Achieved (Yes/no): Body Weight Reduction More Than or Equal to 5%
Description	Number of participants who achieved greater than or equal to (>=) 5% weight loss at 104 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved >=5% weight loss, whereas 'No' infers the number of participants who have not achieved >=5% weight loss. The outcome measure was evaluated based on the data from both in-trial and on-treatment periods. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site. On-treatment observation period: the interval from first to last trial product administration plus 2 weeks of follow-up and excluding any period of temporary treatment interruption defined as >2 consecutive missed doses (corresponding to >2 weeks off-treatment).
Time Frame	At Week 104

Outcome Measure Data

Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure and Number Analyzed = participants with available data for each specified category.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Measure Participants	144	128
Yes	111 73%	44 28.9%
No	33 21.7%	84 55.3%
Yes	110 72.4%	38 25%
No	22 14.5%	71 46.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Semaglutide 2.4 mg, Placebo
	Comments	Treatment policy estimand
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Regression, Logistic
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	4.99
	Confidence Interval	(2-Sided) 95% 2.95 to 8.42
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Semaglutide 2.4 mg, Placebo
	Comments	Hypothetical estimand
	Type of Statistical Test	Superiority
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	MMRM
	Comments

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	18.06
	Confidence Interval	(2-Sided) 95% 10.04 to 32.49
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Number of Participants Who Achieved (Yes/no): Body Weight Reduction More Than or Equal to 10%
Description	Number of participants who achieved >=10% weight loss at 104 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved >=10% weight loss, whereas 'No' infers the number of participants who have not achieved >=10% weight loss. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Time Frame	At Week 104

Outcome Measure Data

Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Measure Participants	144	128
Yes	89 58.6%	17 11.2%
No	55 36.2%	111 73%

4. Secondary Outcome

Title	Number of Participants Who Achieved (Yes/no): Body Weight Reduction More Than or Equal to 15%
Description	Number of participants who achieved >=15% weight loss at 104 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved >=15% weight loss, whereas 'No' infers the number of participants who have not achieved >=15% weight loss. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Time Frame	At Week 104

Outcome Measure Data

Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Measure Participants	144	128
Yes	75 49.3%	9 5.9%
No	69 45.4%	119 78.3%

5. Secondary Outcome

Title	Number of Participants Who Achieved (Yes/no): Body Weight Reduction More Than or Equal to 20%
Description	Number of participants who achieved >=20% weight loss at 104 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved >=20% weight loss, whereas 'No' infers the number of participants who have not achieved >=20% weight loss. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Time Frame	At Week 104

Outcome Measure Data

Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Measure Participants	144	128
Yes	52 34.2%	3 2%
No	92 60.5%	125 82.2%

6. Secondary Outcome

Title	Change From Baseline (Week 0) to Week 104 in Waist Circumference
Description	Change in waist circumference from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Time Frame	From Baseline (Week 0) to Week 104

Outcome Measure Data

Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Measure Participants	143	126
Mean (Standard Deviation) [centimeter (cm)]	-15.2 (12.4)	-4.3 (9.1)

7. Secondary Outcome

Title	Change From Baseline (Week 0) to Week 104 in Body Weight (kg)
Description	Change in body weight from baseline (week 0) to week 104 in kilogram (kg) is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Time Frame	From Baseline (Week 0) to Week 104

Outcome Measure Data

Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Measure Participants	144	128
Mean (Standard Deviation) [kilogram]	-16.9 (14.0)	-2.1 (9.5)

8. Secondary Outcome

Title	Change From Baseline (Week 0) to Week 104 in Body Mass Index (BMI)
Description	Change in BMI from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Time Frame	From Baseline (Week 0) to Week 104

Outcome Measure Data

Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Measure Participants	144	128
Mean (Standard Deviation) [kilogram per square meter (kg/m^2)]	-6.2 (5.3)	-0.7 (3.5)

9. Secondary Outcome

Title	Change From Baseline (Week 0) to Week 104 in Systolic Blood Pressure
Description	Change in systolic blood pressure from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Time Frame	From Baseline (Week 0) to Week 104

Outcome Measure Data

Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Measure Participants	142	125
Mean (Standard Deviation) [millimeter of mercury (mmHg)]	-6 (13)	-1 (15)

10. Secondary Outcome

Title	Change From Baseline (Week 0) to Week 104 in Diastolic Blood Pressure
Description	Change in diastolic blood pressure from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Time Frame	From Baseline (Week 0) to Week 104

Outcome Measure Data

Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Measure Participants	142	125
Mean (Standard Deviation) [mmHg]	-4 (10)	-1 (9)

11. Secondary Outcome

Title	Change in Total Cholesterol-ratio to Baseline
Description	Change in total cholesterol from baseline (week 0) to week 104 measured in milligrams per deciliter (mg/dL) is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Time Frame	From Baseline (Week 0) to Week 104

Outcome Measure Data

Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Measure Participants	141	121
Geometric Mean (Geometric Coefficient of Variation) [Ratio of total cholesterol]	0.96 (15.3)	1.02 (13.5)

12. Secondary Outcome

Title	Change in High Density Lipoprotein (HDL) Cholesterol-ratio to Baseline
Description	Change in HDL cholesterol from baseline (week 0) to week 104 measured in mg/dL is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Time Frame	From Baseline (Week 0) to Week 104

Outcome Measure Data

Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Measure Participants	141	120
Geometric Mean (Geometric Coefficient of Variation) [Ratio of HDL cholesterol]	1.09 (19.1)	1.08 (15.4)

13. Secondary Outcome

Title	Change in Low Density Lipoprotein (LDL) Cholesterol-ratio to Baseline
Description	Change in LDL cholesterol from baseline (week 0) to week 104 measured in mg/dL is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Time Frame	From Baseline (Week 0) to Week 104

Outcome Measure Data

Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Measure Participants	141	121
Geometric Mean (Geometric Coefficient of Variation) [Ratio of LDL cholesterol]	0.93 (23.8)	0.99 (19.1)

14. Secondary Outcome

Title	Change in Very Low Density Lipoprotein (VLDL) Cholesterol-ratio to Baseline
Description	Change in VLDL cholesterol from baseline (week 0) to week 104 measured in mg/dL is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Time Frame	From Baseline (Week 0) to Week 104

Outcome Measure Data

Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Measure Participants	141	121
Geometric Mean (Geometric Coefficient of Variation) [Ratio of VLDL cholesterol]	0.79 (42.3)	1.03 (35.1)

15. Secondary Outcome

Title	Change in Free Fatty Acids-ratio to Baseline
Description	Change in free fatty acids from baseline (week 0) to week 104 measured in mg/dL is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Time Frame	From Baseline (Week 0) to Week 104

Outcome Measure Data

Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Measure Participants	133	111
Geometric Mean (Geometric Coefficient of Variation) [Ratio of free fatty acids]	0.99 (71.2)	1.07 (69.1)

16. Secondary Outcome

Title	Change in Triglycerides-ratio to Baseline
Description	Change in triglycerides from baseline (week 0) to week 104 measured in mg/dL is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Time Frame	From Baseline (Week 0) to Week 104

Outcome Measure Data

Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Measure Participants	141	121
Geometric Mean (Geometric Coefficient of Variation) [Ratio of triglycerides]	0.79 (42.4)	1.03 (36.0)

17. Secondary Outcome

Title	Change in High Sensitivity C-reactive Protein (hsCRP)-Ratio to Baseline
Description	Change in hsCRP from baseline (week 0) to week 104 measured in mg/dL is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Time Frame	From Baseline (Week 0) to Week 104

Outcome Measure Data

Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Measure Participants	141	121
Geometric Mean (Geometric Coefficient of Variation) [Ratio of hsCRP]	0.41 (149.1)	0.99 (105.5)

18. Secondary Outcome

Title	Change in Glycated Haemoglobin (HbA1c) (Percent [%])
Description	Change in HbA1c from baseline (week 0) to week 104 in % is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Time Frame	From Baseline (Week 0) to Week 104

Outcome Measure Data

Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Measure Participants	141	122
Mean (Standard Deviation) [Percent of glycated haemoglobin]	-0.5 (0.3)	-0.1 (0.3)

19. Secondary Outcome

Title	Change From Baseline (Week 0) to Week 104 in HbA1c (mmol/Mol)
Description	Change in HbA1c from baseline (week 0) to week 104 in millimole per mole (mmol/mol) is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Time Frame	From Baseline (Week 0) to Week 104

Outcome Measure Data

Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Measure Participants	141	122
Mean (Standard Deviation) [mmol/mol]	-5.1 (3.2)	-1.0 (3.0)

20. Secondary Outcome

Title	Change From Baseline (Week 0) to Week 104 in Fasting Plasma Glucose (FPG) (mmol/L)
Description	Change in FPG from baseline (week 0) to week 104 in millimoles per liter (mmol/L) is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Time Frame	From Baseline (Week 0) to Week 104

Outcome Measure Data

Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Measure Participants	137	117
Mean (Standard Deviation) [mmol/L]	-0.5 (0.5)	0.1 (0.6)

21. Secondary Outcome

Title	Change From Baseline (Week 0) to Week 104 in FPG (mg/dL)
Description	Change in FPG from baseline (week 0) to week 104 in mg/dL is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Time Frame	From Baseline (Week 0) to Week 104

Outcome Measure Data

Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Measure Participants	137	117
Mean (Standard Deviation) [mg/dL]	-8.3 (9.6)	1.8 (10.8)

22. Secondary Outcome

Title	Change in Fasting Serum Insulin-ratio to Baseline (Pmol/L)
Description	Change in fasting serum insulin from baseline (week 0) to week 104 measured in picomole per liter (pmol) is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Time Frame	From Baseline (Week 0) to Week 104

Outcome Measure Data

Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Measure Participants	131	110
Geometric Mean (Geometric Coefficient of Variation) [Ratio of fasting serum insulin]	0.68 (54.1)	0.96 (62.9)

23. Secondary Outcome

Title	Change in Fasting Serum Insulin-ratio to Baseline (mIU/mL)
Description	Change in fasting serum insulin from baseline (week 0) to week 104 measured in milli-international units per milliliter (mIU/mL) is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.
Time Frame	From Baseline (Week 0) to Week 104

Outcome Measure Data

Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Measure Participants	131	110
Geometric Mean (Geometric Coefficient of Variation) [Ratio of fasting serum insulin]	0.68 (54.1)	0.96 (62.9)

24. Secondary Outcome

Title	Percentage Change From Baseline (Week 0) to Week 52 in Body Weight
Description	Percentage change in body weight from baseline (week 0) to week 52 is presented.
Time Frame	From Baseline (Week 0) to Week 52

Outcome Measure Data

Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Measure Participants	149	129
Mean (Standard Deviation) [percentage change]	-15.8 (9.3)	-3.3 (6.4)

25. Secondary Outcome

Title	Change From Baseline (Week 0) to Week 52 in Body Weight (kg)
Description	Change in body weight from baseline (week 0) to week 52 in kg is presented.
Time Frame	From Baseline (Week 0) to Week 52

Outcome Measure Data

Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Measure Participants	149	129
Mean (Standard Deviation) [kilogram (kg)]	-16.7 (10.3)	-3.5 (7.4)

26. Secondary Outcome

Title	Change From Baseline (Week 0) to Week 52 in Body Mass Index (BMI)
Description	Change in BMI from baseline (week 0) to week 52 is presented.
Time Frame	From Baseline (Week 0) to Week 52

Outcome Measure Data

Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Measure Participants	149	129
Mean (Standard Deviation) [kilogram per square meter (kg/m^2)]	-6.1 (3.8)	-1.3 (2.6)

27. Secondary Outcome

Title	Change From Baseline (Week 0) to Week 52 in Waist Circumference
Description	Change in waist circumference from baseline (week 0) to week 52 is presented.
Time Frame	From Baseline (Week 0) to Week 52

Outcome Measure Data

Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Measure Participants	149	129
Mean (Standard Deviation) [centimeter (cm)]	-14.3 (9.4)	-4.5 (6.8)

28. Secondary Outcome

Title	Number of Participants Who at 52 Weeks Achieved (Yes/no): Body Weight Reduction More Than or Equal to 5%
Description	Number of participants who achieved >=5% weight loss at 52 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved >=5% weight loss, whereas 'No' infers the number of participants who have not achieved >=5% weight loss.
Time Frame	At Week 52

Outcome Measure Data

Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Measure Participants	149	129
Yes	132 86.8%	38 25%
No	17 11.2%	91 59.9%

29. Secondary Outcome

Title	Number of Participants Who at 52 Weeks Achieved (Yes/no): Body Weight Reduction More Than or Equal to 10%
Description	Number of participants who achieved >=10% weight loss at 52 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved >=10% weight loss, whereas 'No' infers the number of participants who have not achieved >=10% weight loss.
Time Frame	At Week 52

Outcome Measure Data

Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Measure Participants	149	129
Yes	102 67.1%	17 11.2%
No	47 30.9%	112 73.7%

30. Secondary Outcome

Title	Number of Participants Who at 52 Weeks Achieved (Yes/no): Body Weight Reduction More Than or Equal to 15%
Description	Number of participants who achieved >=15% weight loss at 52 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved >=15% weight loss, whereas 'No' infers the number of participants who have not achieved >=15% weight loss.
Time Frame	At Week 52

Outcome Measure Data

Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Measure Participants	149	129
Yes	78 51.3%	7 4.6%
No	71 46.7%	122 80.3%

31. Secondary Outcome

Title	Number of Participants Who at 52 Weeks Achieved (Yes/no): Body Weight Reduction More Than or Equal to 20%
Description	Number of participants who achieved >=20% weight loss at 52 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved >=20% weight loss, whereas 'No' infers the number of participants who have not achieved >=20% weight loss.
Time Frame	At Week 52

Outcome Measure Data

Analysis Population Description
The FAS included all randomised participants according to the intention-to-treat principle. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Measure Participants	149	129
Yes	52 34.2%	3 2%
No	97 63.8%	126 82.9%

32. Secondary Outcome

Title	Number of Treatment-emergent Adverse Events (TEAEs)
Description	An adverse event (AE) was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to treatment. The outcome measure was evaluated based on the data from on-treatment observation period, which was defined as the interval from first to last trial product administration plus 7 weeks of follow-up and excluding any period of temporary treatment interruption defined as >7 consecutive missed doses (corresponding to >7 weeks off-treatment).
Time Frame	From Baseline (Week 0) to Week 111

Outcome Measure Data

Analysis Population Description
The safety analysis set (SAS) included all randomised participants exposed to at least one dose of randomised treatment.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Measure Participants	152	152
Number [events]	1645	1059

33. Secondary Outcome

Title	Number of Serious Adverse Events (SAEs)
Description	A SAE was 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 111 is presented. The outcome measure was evaluated based on the data from on-treatment observation period, which was defined as the interval from first to last trial product administration plus 7 weeks of follow-up and excluding any period of temporary treatment interruption defined as >7 consecutive missed doses (corresponding to >7 weeks off-treatment).
Time Frame	From Baseline (Week 0) to Week 111

Outcome Measure Data

Analysis Population Description
The SAS included all randomised participants exposed to at least one dose of randomised treatment.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Measure Participants	152	152
Number [events]	18	20

34. Secondary Outcome

Title	Change From Baseline (Week 0) to Week 104 in Pulse
Description	Change in pulse from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from on-treatment observation period, which was defined as the interval from first to last trial product administration plus 2 weeks of follow-up and excluding any period of temporary treatment interruption defined as >2 consecutive missed doses (corresponding to >2 weeks off-treatment).
Time Frame	From Baseline (Week 0) to Week 104

Outcome Measure Data

Analysis Population Description
The SAS included all randomised participants exposed to at least one dose of randomised treatment. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Measure Participants	130	106
Mean (Standard Deviation) [beats per minute (beats/min)]	3 (10)	-1 (9)

35. Secondary Outcome

Title	Change From Baseline (Week 0) to Week 104 in Amylase
Description	Change in amylase from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from on-treatment observation period, which was defined as the interval from first to last trial product administration plus 2 weeks of follow-up and excluding any period of temporary treatment interruption defined as >2 consecutive missed doses (corresponding to >2 weeks off-treatment).
Time Frame	From Baseline (Week 0) to Week 104

Outcome Measure Data

Analysis Population Description
The SAS included all randomised participants exposed to at least one dose of randomised treatment. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Measure Participants	130	106
Geometric Mean (Geometric Coefficient of Variation) [Units/liter (U/L)]	1.13 (20.7)	1.02 (15.1)

36. Secondary Outcome

Title	Change From Baseline (Week 0) to Week 104 in Lipase
Description	Change in lipase from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from on-treatment observation period, which was defined as the interval from first to last trial product administration plus 2 weeks of follow-up and excluding any period of temporary treatment interruption defined as >2 consecutive missed doses (corresponding to >2 weeks off-treatment).
Time Frame	From Baseline (Week 0) to Week 104

Outcome Measure Data

Analysis Population Description
The SAS included all randomised participants exposed to at least one dose of randomised treatment. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Measure Participants	130	106
Geometric Mean (Geometric Coefficient of Variation) [U/L]	1.47 (52.3)	1.00 (34.4)

37. Secondary Outcome

Title	Change From Baseline (Week 0) to Week 104 in Calcitonin
Description	Change in calcitonin from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from on-treatment observation period, which was defined as the interval from first to last trial product administration plus 2 weeks of follow-up and excluding any period of temporary treatment interruption defined as >2 consecutive missed doses (corresponding to >2 weeks off-treatment).
Time Frame	From Baseline (Week 0) to Week 104

Outcome Measure Data

Analysis Population Description
The SAS included all randomised participants exposed to at least one dose of randomised treatment. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Measure Participants	124	102
Geometric Mean (Geometric Coefficient of Variation) [nanogram per liter (ng/L)]	0.99 (21.5)	0.97 (41.0)

Adverse Events

	Semaglutide 2.4 mg		Placebo
Time Frame	From Baseline (Week 0) to Week 111
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. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.

Arm/Group Title	Semaglutide 2.4 mg		Placebo
Arm/Group Description	Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.		Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/152 (0.7%)		0/152 (0%)
Serious Adverse Events
	Semaglutide 2.4 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/152 (7.9%)		18/152 (11.8%)
Cardiac disorders
Acute myocardial infarction	1/152 (0.7%)	1	0/152 (0%)	0
Congenital, familial and genetic disorders
Arnold-Chiari malformation	0/152 (0%)	0	1/152 (0.7%)	1
Gastrointestinal disorders
Abdominal adhesions	1/152 (0.7%)	1	0/152 (0%)	0
Gastritis	0/152 (0%)	0	1/152 (0.7%)	1
Gastrooesophageal reflux disease	1/152 (0.7%)	1	0/152 (0%)	0
Hepatobiliary disorders
Cholecystitis	1/152 (0.7%)	1	0/152 (0%)	0
Cholecystitis acute	1/152 (0.7%)	1	0/152 (0%)	0
Cholelithiasis	2/152 (1.3%)	2	0/152 (0%)	0
Infections and infestations
Anal abscess	0/152 (0%)	0	1/152 (0.7%)	1
Appendicitis	0/152 (0%)	0	1/152 (0.7%)	1
Appendicitis perforated	1/152 (0.7%)	1	0/152 (0%)	0
COVID-19	1/152 (0.7%)	1	2/152 (1.3%)	2
COVID-19 pneumonia	0/152 (0%)	0	1/152 (0.7%)	1
Colonic abscess	1/152 (0.7%)	1	0/152 (0%)	0
Diverticulitis	1/152 (0.7%)	1	0/152 (0%)	0
Herpes zoster	0/152 (0%)	0	1/152 (0.7%)	1
Perineal abscess	1/152 (0.7%)	1	0/152 (0%)	0
Pneumonia	0/152 (0%)	0	1/152 (0.7%)	1
Injury, poisoning and procedural complications
Jaw fracture	0/152 (0%)	0	1/152 (0.7%)	1
Rib fracture	0/152 (0%)	0	1/152 (0.7%)	1
Musculoskeletal and connective tissue disorders
Foot deformity	1/152 (0.7%)	1	1/152 (0.7%)	1
Rotator cuff syndrome	0/152 (0%)	0	1/152 (0.7%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign uterine neoplasm	1/152 (0.7%)	1	0/152 (0%)	0
Invasive ductal breast carcinoma	0/152 (0%)	0	2/152 (1.3%)	2
Lung adenocarcinoma	0/152 (0%)	0	1/152 (0.7%)	1
Small cell lung cancer metastatic	0/152 (0%)	0	1/152 (0.7%)	1
Nervous system disorders
Cervical cord compression	0/152 (0%)	0	1/152 (0.7%)	1
Tension headache	0/152 (0%)	0	1/152 (0.7%)	1
Psychiatric disorders
Panic disorder	1/152 (0.7%)	1	0/152 (0%)	0
Renal and urinary disorders
Nephrolithiasis	1/152 (0.7%)	1	0/152 (0%)	0
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism	1/152 (0.7%)	1	0/152 (0%)	0
Surgical and medical procedures
Thyroidectomy	0/152 (0%)	0	1/152 (0.7%)	1
Vascular disorders
Deep vein thrombosis	1/152 (0.7%)	1	0/152 (0%)	0
Other (Not Including Serious) Adverse Events
	Semaglutide 2.4 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	141/152 (92.8%)		117/152 (77%)
Gastrointestinal disorders
Abdominal distension	15/152 (9.9%)	22	9/152 (5.9%)	13
Abdominal pain	20/152 (13.2%)	32	4/152 (2.6%)	14
Abdominal pain upper	22/152 (14.5%)	23	10/152 (6.6%)	13
Constipation	47/152 (30.9%)	62	17/152 (11.2%)	26
Diarrhoea	53/152 (34.9%)	108	36/152 (23.7%)	51
Dyspepsia	20/152 (13.2%)	24	7/152 (4.6%)	12
Eructation	17/152 (11.2%)	21	1/152 (0.7%)	2
Flatulence	20/152 (13.2%)	25	10/152 (6.6%)	11
Gastrooesophageal reflux disease	15/152 (9.9%)	19	6/152 (3.9%)	6
Nausea	81/152 (53.3%)	213	33/152 (21.7%)	53
Vomiting	46/152 (30.3%)	78	7/152 (4.6%)	8
General disorders
Asthenia	8/152 (5.3%)	10	2/152 (1.3%)	3
Fatigue	11/152 (7.2%)	12	8/152 (5.3%)	8
Injection site bruising	5/152 (3.3%)	8	8/152 (5.3%)	11
Infections and infestations
Bronchitis	8/152 (5.3%)	9	8/152 (5.3%)	9
COVID-19	15/152 (9.9%)	16	6/152 (3.9%)	6
Gastroenteritis	20/152 (13.2%)	28	4/152 (2.6%)	4
Influenza	20/152 (13.2%)	23	16/152 (10.5%)	19
Nasopharyngitis	24/152 (15.8%)	33	23/152 (15.1%)	31
Sinusitis	8/152 (5.3%)	8	9/152 (5.9%)	9
Upper respiratory tract infection	20/152 (13.2%)	31	23/152 (15.1%)	30
Urinary tract infection	12/152 (7.9%)	19	6/152 (3.9%)	7
Injury, poisoning and procedural complications
Ligament sprain	10/152 (6.6%)	10	1/152 (0.7%)	1
Metabolism and nutrition disorders
Decreased appetite	17/152 (11.2%)	18	6/152 (3.9%)	6
Musculoskeletal and connective tissue disorders
Arthralgia	14/152 (9.2%)	20	11/152 (7.2%)	20
Back pain	15/152 (9.9%)	17	19/152 (12.5%)	20
Osteoarthritis	9/152 (5.9%)	10	8/152 (5.3%)	9
Nervous system disorders
Dizziness	13/152 (8.6%)	16	8/152 (5.3%)	12
Headache	16/152 (10.5%)	36	16/152 (10.5%)	31
Psychiatric disorders
Anxiety	8/152 (5.3%)	8	11/152 (7.2%)	12
Respiratory, thoracic and mediastinal disorders
Cough	8/152 (5.3%)	8	8/152 (5.3%)	10
Vascular disorders
Hypertension	6/152 (3.9%)	6	14/152 (9.2%)	14

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

Results Point of Contact

Name/Title	Clinical Reporting Office (1452)
Organization	Novo Nordisk A/S
Phone	(+1) 866-867-7178
Email	clinicaltrials@novonordisk.com

Responsible Party:

Novo Nordisk A/S

ClinicalTrials.gov Identifier:

NCT03693430

Other Study ID Numbers:

NN9536-4378
2017-003726-32
U1111-1202-1740

First Posted:

Oct 3, 2018

Last Update Posted:

Mar 23, 2022

Last Verified:

Mar 1, 2022

STEP 5: Two-year Research Study Investigating How Well Semaglutide Works in People Suffering From Overweight or Obesity

Study Details

Study Description

Brief Summary

Study Design

Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

Eligibility Criteria

Criteria

Inclusion Criteria:

Exclusion criteria:

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Locations

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Investigators

Study Documents (Full-Text)

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Study Results

Participant Flow

Baseline Characteristics

Outcome Measures

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Outcome Measure Data

Statistical Analysis 1

Statistical Analysis 2

Outcome Measure Data

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Outcome Measure Data

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Adverse Events

All Cause Mortality

Serious Adverse Events

Other (Not Including Serious) Adverse Events

Limitations/Caveats

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Results Point of Contact