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

• ClinicalTrials.gov Identifier: NCT03552757
• Recruitment Status: Completed
• First Posted: June 12, 2018
• Results First Posted: August 11, 2021
• Last Update Posted: November 9, 2021
• Sponsor: Novo Nordisk A/S
• Information provided by (Responsible Party): Novo Nordisk A/S

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Conditions: Obesity; Overweight
• Interventions: Drug: Semaglutide 1.0 mg; Drug: Semaglutide 2.4 mg; Drug: Placebo I (Semaglutide); Drug: Placebo II (Semaglutide)
• Enrollment: 1210

Participant Flow

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

Arm/Group Title	Semaglutide 1.0 mg	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants received once-weekly subcutaneous (s.c; under the skin) semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Period Title: Overall Study
Started	403	404	403
Exposed	402	403	402
Full Analysis Set (FAS)	403	404	403
Safety Analysis Set (SAS)	402	403	402
Completed	390	391	383
Not Completed	13	13	20
Reason Not Completed
Withdrawal by Subject	10	5	12
Lost to Follow-up	2	7	7
Death	1	1	1

Baseline Characteristics

Arm/Group Title		Semaglutide 1.0 mg	Semaglutide 2.4 mg	Placebo	Total
Arm/Group Description		Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Total of all reporting groups
Overall Number of Baseline Participants		403	404	403	1210
Baseline Analysis Population Description		Full analysis set (FAS) which comprised all randomised participants.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Year
	Number Analyzed	403 participants	404 participants	403 participants	1210 participants
		56 (10)	55 (11)	55 (11)	55 (11)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	403 participants	404 participants	403 participants	1210 participants
	Female	203 50.4%	223 55.2%	190 47.1%	616 50.9%
	Male	200 49.6%	181 44.8%	213 52.9%	594 49.1%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	403 participants	404 participants	403 participants	1210 participants
	White	272 67.5%	237 58.7%	242 60.0%	751 62.1%
	Asian	97 24.1%	112 27.7%	108 26.8%	317 26.2%
	Black or African American	28 6.9%	35 8.7%	37 9.2%	100 8.3%
	Other	6 1.5%	16 4.0%	13 3.2%	35 2.9%
	American Indian or Alaska Native	0 0.0%	4 1.0%	2 0.5%	6 0.5%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	1 0.2%	1 0.1%
	Not Applicable	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	403 participants	404 participants	403 participants	1210 participants
	Not Hispanic or Latino	344 85.4%	357 88.4%	354 87.8%	1055 87.2%
	Hispanic or Latino	59 14.6%	47 11.6%	49 12.2%	155 12.8%
	Not Applicable	0 0.0%	0 0.0%	0 0.0%	0 0.0%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title		Semaglutide 2.4 mg	Placebo
Arm/Group Description:		Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Overall Number of Participants Analyzed		404	403
Mean (Standard Deviation); Unit of Measure: Percentage point of body weight
In-trial observation period	Number Analyzed	388 participants	376 participants
		-9.9 (8.0)	-3.3 (5.5)
On-treatment observation period	Number Analyzed	351 participants	340 participants
		-10.7 (7.8)	-3.1 (5.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Semaglutide 2.4 mg, Placebo
	Comments	Results are based on the data from in-trial observation period. Week 68 responses were analysed using an analysis of covariance model (ANCOVA) with randomised treatment, stratification groups (oral anti-diabetic (OAD) treatment status and HbA1c category at screening) and the interaction between stratification groups as factors and baseline body weight as covariate.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-6.21
	Confidence Interval	(2-Sided) 95%; -7.28 to -5.15
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Semaglutide 2.4 mg, Placebo
	Comments	Results are based on the data from on-treatment observation period. All responses prior to first discontinuation of treatment (or initiation of other anti-obesity medication or bariatric surgery) were included in a mixed model for repeated measurements (MMRM) with randomised treatment, stratification groups (OAD treatment status and HbA1c category at screening) and the interaction between stratification groups as factors and baseline body weight as covariate, all nested within visit.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	MMRM
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-7.57
	Confidence Interval	(2-Sided) 95%; -8.56 to -6.58
	Estimation Comments	[Not Specified]

2. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title		Semaglutide 2.4 mg	Placebo
Arm/Group Description:		Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Overall Number of Participants Analyzed		404	403
Measure Type: Count of Participants; Unit of Measure: Participants
In-trial observation period	Number Analyzed	388 participants	376 participants
	Yes	267 68.8%	107 28.5%
	No	121 31.2%	269 71.5%
On-treatment observation period	Number Analyzed	351 participants	340 participants
	Yes	257 73.2%	94 27.6%
	No	94 26.8%	246 72.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Semaglutide 2.4 mg, Placebo
	Comments	Results are based on the data from in-trial observation period. Week 68 responses were analysed using a binary logistic regression model with randomised treatment, stratification groups (OAD treatment status and HbA1c category at screening) and the interaction between stratification groups as factors and baseline body weight as covariate.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	4.88
	Confidence Interval	(2-Sided) 95%; 3.58 to 6.64
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Semaglutide 2.4 mg, Placebo
	Comments	Results are based on the data from on-treatment observation period. All responses prior to first discontinuation of treatment (or initiation of other anti-obesity medication or bariatric surgery) were included in a MMRM with randomised treatment, stratification groups (OAD treatment status and HbA1c category at screening) and the interaction between stratification groups as factors and baseline body weight as covariate, all nested within visit.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	8.69
	Confidence Interval	(2-Sided) 95%; 6.31 to 11.97
	Estimation Comments	[Not Specified]

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Semaglutide 1.0 mg
Arm/Group Description:	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Overall Number of Participants Analyzed	388	380
Measure Type: Count of Participants; Unit of Measure: Participants
Yes	267 68.8%	217 57.1%
No	121 31.2%	163 42.9%

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

8. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 1.0 mg	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Overall Number of Participants Analyzed	380	388	376
Measure Type: Count of Participants; Unit of Measure: Participants
Yes	109 28.7%	177 45.6%	31 8.2%
No	271 71.3%	211 54.4%	345 91.8%

9. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 1.0 mg	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Overall Number of Participants Analyzed	380	388	376
Measure Type: Count of Participants; Unit of Measure: Participants
Yes	52 13.7%	100 25.8%	12 3.2%
No	328 86.3%	288 74.2%	364 96.8%

10. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 1.0 mg	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Overall Number of Participants Analyzed	380	388	376
Measure Type: Count of Participants; Unit of Measure: Participants
Yes	18 4.7%	51 13.1%	6 1.6%
No	362 95.3%	337 86.9%	370 98.4%

11. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

12. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

13. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

14. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

15. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 1.0 mg	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Overall Number of Participants Analyzed	376	381	374
Measure Type: Count of Participants; Unit of Measure: Participants
Yes	272 72.3%	299 78.5%	99 26.5%
No	104 27.7%	82 21.5%	275 73.5%

16. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 1.0 mg	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Overall Number of Participants Analyzed	376	381	374
Measure Type: Count of Participants; Unit of Measure: Participants
Yes	226 60.1%	257 67.5%	58 15.5%
No	150 39.9%	124 32.5%	316 84.5%

17. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 1.0 mg	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Overall Number of Participants Analyzed	376	381	374
Measure Type: Count of Participants; Unit of Measure: Participants
Yes	105 27.9%	170 44.6%	25 6.7%
No	271 72.1%	211 55.4%	349 93.3%

18. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 1.0 mg	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Overall Number of Participants Analyzed	376	381	374
Measure Type: Count of Participants; Unit of Measure: Participants
Yes	49 13.0%	98 25.7%	11 2.9%
No	327 87.0%	283 74.3%	363 97.1%

19. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

20. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

21. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

22. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

23. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

24. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

25. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

26. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

27. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

28. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

29. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

30. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

31. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

32. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

33. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 1.0 mg	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Overall Number of Participants Analyzed	370	376	365
Measure Type: Count of Participants; Unit of Measure: Participants
Yes (with threshold 4.3)	88 23.8%	111 29.5%	68 18.6%
No (with threshold 4.3)	282 76.2%	265 70.5%	297 81.4%
Yes (with threshold 3.7)	130 35.1%	158 42.0%	102 27.9%
No (with threshold 3.7)	240 64.9%	218 58.0%	263 72.1%

34. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 1.0 mg	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.	Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
Overall Number of Participants Analyzed	369	376	365
Measure Type: Count of Participants; Unit of Measure: Participants
Yes (with threshold 20)	107 29.0%	131 34.8%	83 22.7%
No (with threshold 20)	262 71.0%	245 65.2%	282 77.3%
Yes (with threshold 14.6)	144 39.0%	160 42.6%	113 31.0%
No (with threshold 14.6)	225 61.0%	216 57.4%	252 69.0%

35. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

36. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

37. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

38. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

39. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

40. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

41. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

Adverse Events

Time Frame	Week 0 to week 75. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.
Adverse Event Reporting Description	All presented AEs are treatment-emergent (i.e., TEAEs).
Arm/Group Title	Semaglutide 1.0 mg		Semaglutide 2.4 mg		Placebo
Arm/Group Description	Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8 and 1.0 mg from week 9-68. Participants also received once-weekly placebo I (placebo matched to semaglutide 2.4 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.		Participants received once-weekly s.c semaglutide injections for 68 weeks: 0.25 mg from week 1-4, 0.5 mg from week 5-8, 1.0 mg from week 9-12, 1.7 mg from week 13-16 and 2.4 mg from week 17-68. Participants also received once-weekly placebo II (placebo matched to semaglutide 1.0 mg) s.c. injection for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.		Participants received once-weekly s.c placebo injections (both placebo I (placebo matched to semaglutide 1.0 mg) and placebo II (placebo matched to semaglutide 2.4 mg) for 68 weeks. Participants received the treatments as an adjunct to a reduced calorie diet and increased physical activity.
All-Cause Mortality
	Semaglutide 1.0 mg		Semaglutide 2.4 mg		Placebo
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	1/402 (0.25%)		1/403 (0.25%)		1/402 (0.25%)
Serious Adverse Events
	Semaglutide 1.0 mg		Semaglutide 2.4 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/402 (7.71%)		40/403 (9.93%)		37/402 (9.20%)
Cardiac disorders
Acute myocardial infarction † 1	2/402 (0.50%)	2	1/403 (0.25%)	1	1/402 (0.25%)	1
Angina pectoris † 1	1/402 (0.25%)	1	0/403 (0.00%)	0	1/402 (0.25%)	1
Angina unstable † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	0/402 (0.00%)	0
Atrial fibrillation † 1	2/402 (0.50%)	2	2/403 (0.50%)	2	2/402 (0.50%)	2
Bradycardia † 1	1/402 (0.25%)	1	0/403 (0.00%)	0	0/402 (0.00%)	0
Cardiac failure acute † 1	0/402 (0.00%)	0	0/403 (0.00%)	0	1/402 (0.25%)	1
Cardiac failure congestive † 1	1/402 (0.25%)	1	1/403 (0.25%)	1	1/402 (0.25%)	1
Myocardial infarction † 1	1/402 (0.25%)	1	1/403 (0.25%)	1	0/402 (0.00%)	0
Myocardial ischaemia † 1	1/402 (0.25%)	1	0/403 (0.00%)	0	0/402 (0.00%)	0
Supraventricular tachycardia † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	0/402 (0.00%)	0
Eye disorders
Cataract † 1	0/402 (0.00%)	0	0/403 (0.00%)	0	1/402 (0.25%)	1
Glaucoma † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	0/402 (0.00%)	0
Gastrointestinal disorders
Abdominal pain † 1	3/402 (0.75%)	3	0/403 (0.00%)	0	0/402 (0.00%)	0
Diarrhoea † 1	1/402 (0.25%)	1	0/403 (0.00%)	0	0/402 (0.00%)	0
Diverticular perforation † 1	0/402 (0.00%)	0	0/403 (0.00%)	0	1/402 (0.25%)	1
Food poisoning † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	0/402 (0.00%)	0
Gastric ulcer † 1	1/402 (0.25%)	1	0/403 (0.00%)	0	0/402 (0.00%)	0
Gastritis † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	0/402 (0.00%)	0
Inguinal hernia † 1	0/402 (0.00%)	0	0/403 (0.00%)	0	1/402 (0.25%)	1
Nausea † 1	2/402 (0.50%)	2	1/403 (0.25%)	1	0/402 (0.00%)	0
Obstructive pancreatitis † 1	0/402 (0.00%)	0	0/403 (0.00%)	0	1/402 (0.25%)	1
Small intestinal obstruction † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	0/402 (0.00%)	0
Upper gastrointestinal haemorrhage † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	0/402 (0.00%)	0
Vomiting † 1	0/402 (0.00%)	0	2/403 (0.50%)	2	0/402 (0.00%)	0
General disorders
Chest pain † 1	0/402 (0.00%)	0	0/403 (0.00%)	0	1/402 (0.25%)	1
Hepatobiliary disorders
Cholecystitis acute † 1	0/402 (0.00%)	0	0/403 (0.00%)	0	1/402 (0.25%)	1
Cholecystitis chronic † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	0/402 (0.00%)	0
Cholelithiasis † 1	1/402 (0.25%)	1	1/403 (0.25%)	1	0/402 (0.00%)	0
Non-alcoholic steatohepatitis † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	0/402 (0.00%)	0
Immune system disorders
Immunisation reaction † 1	1/402 (0.25%)	1	0/403 (0.00%)	0	0/402 (0.00%)	0
Infections and infestations
Appendicitis † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	1/402 (0.25%)	1
Bronchitis † 1	0/402 (0.00%)	0	0/403 (0.00%)	0	1/402 (0.25%)	1
Cellulitis † 1	2/402 (0.50%)	2	0/403 (0.00%)	0	1/402 (0.25%)	1
Colonic abscess † 1	0/402 (0.00%)	0	0/403 (0.00%)	0	1/402 (0.25%)	1
Cystitis † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	0/402 (0.00%)	0
Diverticulitis † 1	1/402 (0.25%)	1	0/403 (0.00%)	0	1/402 (0.25%)	1
Empyema † 1	0/402 (0.00%)	0	0/403 (0.00%)	0	1/402 (0.25%)	1
Gastroenteritis † 1	3/402 (0.75%)	3	3/403 (0.74%)	3	1/402 (0.25%)	1
Herpes zoster † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	0/402 (0.00%)	0
Joint abscess † 1	0/402 (0.00%)	0	0/403 (0.00%)	0	1/402 (0.25%)	1
Kidney infection † 1	0/402 (0.00%)	0	0/403 (0.00%)	0	1/402 (0.25%)	1
Osteomyelitis † 1	0/402 (0.00%)	0	0/403 (0.00%)	0	1/402 (0.25%)	1
Pharyngitis streptococcal † 1	0/402 (0.00%)	0	0/403 (0.00%)	0	1/402 (0.25%)	1
Pneumonia † 1	1/402 (0.25%)	1	1/403 (0.25%)	1	2/402 (0.50%)	2
Pneumonia influenzal † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	0/402 (0.00%)	0
Postoperative wound infection † 1	1/402 (0.25%)	1	0/403 (0.00%)	0	0/402 (0.00%)	0
Respiratory tract infection † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	0/402 (0.00%)	0
Sepsis † 1	3/402 (0.75%)	3	0/403 (0.00%)	0	0/402 (0.00%)	0
Urosepsis † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	0/402 (0.00%)	0
Viral infection † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	0/402 (0.00%)	0
Wound infection staphylococcal † 1	0/402 (0.00%)	0	0/403 (0.00%)	0	1/402 (0.25%)	1
Injury, poisoning and procedural complications
Anaemia postoperative † 1	0/402 (0.00%)	0	0/403 (0.00%)	0	1/402 (0.25%)	1
Ankle fracture † 1	1/402 (0.25%)	1	0/403 (0.00%)	0	0/402 (0.00%)	0
Cervical vertebral fracture † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	0/402 (0.00%)	0
Fall † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	0/402 (0.00%)	0
Hip fracture † 1	1/402 (0.25%)	1	0/403 (0.00%)	0	0/402 (0.00%)	0
Humerus fracture † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	0/402 (0.00%)	0
Joint dislocation † 1	0/402 (0.00%)	0	0/403 (0.00%)	0	1/402 (0.25%)	1
Ligament rupture † 1	1/402 (0.25%)	1	0/403 (0.00%)	0	0/402 (0.00%)	0
Lisfranc fracture † 1	0/402 (0.00%)	0	0/403 (0.00%)	0	1/402 (0.25%)	1
Post procedural haemorrhage † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	0/402 (0.00%)	0
Rib fracture † 1	0/402 (0.00%)	0	2/403 (0.50%)	2	0/402 (0.00%)	0
Road traffic accident † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	0/402 (0.00%)	0
Skin laceration † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	0/402 (0.00%)	0
Spinal compression fracture † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	0/402 (0.00%)	0
Subdural haematoma † 1	0/402 (0.00%)	0	0/403 (0.00%)	0	1/402 (0.25%)	1
Thoracic vertebral fracture † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	0/402 (0.00%)	0
Traumatic haemothorax † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	0/402 (0.00%)	0
Upper limb fracture † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	0/402 (0.00%)	0
Metabolism and nutrition disorders
Cachexia † 1	1/402 (0.25%)	1	0/403 (0.00%)	0	0/402 (0.00%)	0
Decreased appetite † 1	1/402 (0.25%)	1	0/403 (0.00%)	0	0/402 (0.00%)	0
Dehydration † 1	2/402 (0.50%)	2	1/403 (0.25%)	1	1/402 (0.25%)	1
Diabetes mellitus inadequate control † 1	0/402 (0.00%)	0	0/403 (0.00%)	0	1/402 (0.25%)	1
Diabetic ketoacidosis † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	0/402 (0.00%)	0
Diabetic metabolic decompensation † 1	0/402 (0.00%)	0	0/403 (0.00%)	0	1/402 (0.25%)	1
Hyperglycaemia † 1	1/402 (0.25%)	1	0/403 (0.00%)	0	0/402 (0.00%)	0
Hyponatraemia † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	0/402 (0.00%)	0
Ketoacidosis † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	0/402 (0.00%)	0
Lactic acidosis † 1	1/402 (0.25%)	1	0/403 (0.00%)	0	0/402 (0.00%)	0
Obesity † 1	0/402 (0.00%)	0	0/403 (0.00%)	0	1/402 (0.25%)	1
Musculoskeletal and connective tissue disorders
Neuropathic arthropathy † 1	0/402 (0.00%)	0	0/403 (0.00%)	0	1/402 (0.25%)	1
Osteoarthritis † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	0/402 (0.00%)	0
Pain in extremity † 1	0/402 (0.00%)	0	0/403 (0.00%)	0	1/402 (0.25%)	1
Rotator cuff syndrome † 1	1/402 (0.25%)	1	0/403 (0.00%)	0	0/402 (0.00%)	0
Spondylolisthesis † 1	1/402 (0.25%)	1	0/403 (0.00%)	0	0/402 (0.00%)	0
Trigger finger † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	0/402 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma gastric † 1	1/402 (0.25%)	1	0/403 (0.00%)	0	0/402 (0.00%)	0
Adenocarcinoma of colon † 1	1/402 (0.25%)	1	0/403 (0.00%)	0	0/402 (0.00%)	0
Gastric cancer † 1	0/402 (0.00%)	0	0/403 (0.00%)	0	1/402 (0.25%)	1
Gastric cancer stage IV † 1	0/402 (0.00%)	0	0/403 (0.00%)	0	1/402 (0.25%)	1
Gastrointestinal lymphoma † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	0/402 (0.00%)	0
Gastrointestinal stromal tumour † 1	1/402 (0.25%)	1	0/403 (0.00%)	0	0/402 (0.00%)	0
Hepatocellular carcinoma † 1	0/402 (0.00%)	0	0/403 (0.00%)	0	1/402 (0.25%)	1
Invasive ductal breast carcinoma † 1	1/402 (0.25%)	1	0/403 (0.00%)	0	0/402 (0.00%)	0
Keratinising squamous cell carcinoma of nasopharynx † 1	0/402 (0.00%)	0	0/403 (0.00%)	0	1/402 (0.25%)	1
Myeloid leukaemia † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	0/402 (0.00%)	0
Neuroendocrine tumour † 1	1/402 (0.25%)	1	0/403 (0.00%)	0	0/402 (0.00%)	0
Prostate cancer † 1	0/402 (0.00%)	0	0/403 (0.00%)	0	2/402 (0.50%)	2
Uterine cancer † 1	1/402 (0.25%)	1	0/403 (0.00%)	0	0/402 (0.00%)	0
Nervous system disorders
Cerebral artery thrombosis † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	0/402 (0.00%)	0
Cerebral infarction † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	0/402 (0.00%)	0
Cerebrovascular accident † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	1/402 (0.25%)	1
Hepatic encephalopathy † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	0/402 (0.00%)	0
Hyperaesthesia † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	0/402 (0.00%)	0
Hyponatraemic encephalopathy † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	0/402 (0.00%)	0
Ischaemic stroke † 1	1/402 (0.25%)	1	0/403 (0.00%)	0	1/402 (0.25%)	1
Presyncope † 1	0/402 (0.00%)	0	0/403 (0.00%)	0	1/402 (0.25%)	1
Spinal epidural haematoma † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	0/402 (0.00%)	0
Subarachnoid haemorrhage † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	0/402 (0.00%)	0
Syncope † 1	1/402 (0.25%)	1	1/403 (0.25%)	1	0/402 (0.00%)	0
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous † 1	0/402 (0.00%)	0	0/403 (0.00%)	0	1/402 (0.25%)	1
Renal and urinary disorders
Acute kidney injury † 1	2/402 (0.50%)	2	2/403 (0.50%)	3	1/402 (0.25%)	1
Bladder outlet obstruction † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	0/402 (0.00%)	0
Stag horn calculus † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	0/402 (0.00%)	0
Ureterolithiasis † 1	0/402 (0.00%)	0	0/403 (0.00%)	0	2/402 (0.50%)	2
Reproductive system and breast disorders
Uterine polyp † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	0/402 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure † 1	1/402 (0.25%)	1	1/403 (0.25%)	1	0/402 (0.00%)	0
Asthma † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	1/402 (0.25%)	1
Pneumothorax † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	0/402 (0.00%)	0
Surgical and medical procedures
Cardiac pacemaker replacement † 1	1/402 (0.25%)	1	0/403 (0.00%)	0	0/402 (0.00%)	0
Sperm aspiration † 1	0/402 (0.00%)	0	0/403 (0.00%)	0	1/402 (0.25%)	1
Stent placement † 1	0/402 (0.00%)	0	0/403 (0.00%)	0	1/402 (0.25%)	1
Thyroidectomy † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	0/402 (0.00%)	0
Vascular disorders
Aortic rupture † 1	0/402 (0.00%)	0	1/403 (0.25%)	1	0/402 (0.00%)	0
Hypertension † 1	0/402 (0.00%)	0	2/403 (0.50%)	2	0/402 (0.00%)	0
Hypertensive urgency † 1	0/402 (0.00%)	0	0/403 (0.00%)	0	1/402 (0.25%)	1
Shock † 1	1/402 (0.25%)	1	0/403 (0.00%)	0	0/402 (0.00%)	0
1 Term from vocabulary, MedDRA 22; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Semaglutide 1.0 mg		Semaglutide 2.4 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	261/402 (64.93%)		284/403 (70.47%)		190/402 (47.26%)
Gastrointestinal disorders
Abdominal distension † 1	9/402 (2.24%)	12	24/403 (5.96%)	30	11/402 (2.74%)	13
Constipation † 1	51/402 (12.69%)	70	70/403 (17.37%)	82	22/402 (5.47%)	26
Diarrhoea † 1	88/402 (21.89%)	157	86/403 (21.34%)	141	48/402 (11.94%)	66
Dyspepsia † 1	27/402 (6.72%)	27	25/403 (6.20%)	30	5/402 (1.24%)	5
Flatulence † 1	21/402 (5.22%)	25	16/403 (3.97%)	21	7/402 (1.74%)	9
Nausea † 1	128/402 (31.84%)	196	135/403 (33.50%)	248	37/402 (9.20%)	45
Vomiting † 1	54/402 (13.43%)	93	86/403 (21.34%)	186	11/402 (2.74%)	12
General disorders
Fatigue † 1	19/402 (4.73%)	26	28/403 (6.95%)	29	4/402 (1.00%)	4
Infections and infestations
Gastroenteritis † 1	21/402 (5.22%)	25	11/403 (2.73%)	12	12/402 (2.99%)	14
Nasopharyngitis † 1	47/402 (11.69%)	69	68/403 (16.87%)	115	59/402 (14.68%)	92
Upper respiratory tract infection † 1	37/402 (9.20%)	54	42/403 (10.42%)	48	38/402 (9.45%)	50
Metabolism and nutrition disorders
Decreased appetite † 1	29/402 (7.21%)	33	38/403 (9.43%)	41	15/402 (3.73%)	17
Musculoskeletal and connective tissue disorders
Arthralgia † 1	24/402 (5.97%)	27	23/403 (5.71%)	29	20/402 (4.98%)	20
Back pain † 1	28/402 (6.97%)	30	27/403 (6.70%)	30	14/402 (3.48%)	15
Nervous system disorders
Headache † 1	33/402 (8.21%)	48	31/403 (7.69%)	40	20/402 (4.98%)	27
1 Term from vocabulary, MedDRA 22; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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 Transparency Anchor and Disclosure (1452)
• Organization: Novo Nordisk A/S
• Phone: (+1) 866-867-7178
• EMail: clinicaltrials@novonordisk.com

Publications of Results:

Davies M, Faerch L, Jeppesen OK, Pakseresht A, Pedersen SD, Perreault L, Rosenstock J, Shimomura I, Viljoen A, Wadden TA, Lingvay I; STEP 2 Study Group. Semaglutide 2.4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial. Lancet. 2021 Mar 13;397(10278):971-984. doi: 10.1016/S0140-6736(21)00213-0. Epub 2021 Mar 2.

Other 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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

O'Neil PM, Birkenfeld AL, McGowan B, Mosenzon O, Pedersen SD, Wharton S, Carson CG, Jepsen CH, Kabisch M, Wilding JPH. Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial. Lancet. 2018 Aug 25;392(10148):637-649. doi: 10.1016/S0140-6736(18)31773-2. Epub 2018 Aug 16.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT03552757
• Other Study ID Numbers: NN9536-4374; U1111-1200-8148 ( Other Identifier: World Health Organization (WHO) ); 2017-003414-10 ( Other Identifier: European Medicines Agency (EudraCT) )
• First Submitted: May 30, 2018
• First Posted: June 12, 2018
• Results First Submitted: June 16, 2021
• Results First Posted: August 11, 2021
• Last Update Posted: November 9, 2021