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

• ClinicalTrials.gov Identifier: NCT03611582
• Recruitment Status: Completed
• First Posted: August 2, 2018
• Results First Posted: July 9, 2021
• Last Update Posted: November 11, 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: Overweight; Obesity
• Interventions: Drug: Semaglutide; Drug: Placebo (semaglutide)
• Enrollment: 611

Participant Flow

Recruitment Details	The trial was conducted in 41 sites in the United States.
Pre-assignment Details	The trial has a 68-week treatment period (16 weeks of dose escalation and 52 weeks of maintenance dose). Participants were randomised in 2:1 ratio either to receive semaglutide 2.4 mg or placebo.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.	Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Period Title: Overall Study
Started	407	204
Full Analysis Set (FAS)	407	204
Safety Analysis Set (SAS)	407	204
Completed	339	166
Not Completed	68	38
Reason Not Completed
Adverse Event	26	6
Protocol Violation	0	1
Pregnancy	1	2
Lack of Efficacy	0	1
At the discretion of the investigator	1	0
Safety concern as judged by the investigator	1	2
Withdrawal by Subject	4	3
Lost to Follow-up	18	7
other	17	16

Baseline Characteristics

Arm/Group Title		Semaglutide 2.4 mg	Placebo	Total
Arm/Group Description		Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.	Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.	Total of all reporting groups
Overall Number of Baseline Participants		407	204	611
Baseline Analysis Population Description		Full analysis set (FAS) included all randomised participants.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	407 participants	204 participants	611 participants
		46 (13)	46 (13)	46 (13)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	407 participants	204 participants	611 participants
	Female	315 77.4%	180 88.2%	495 81.0%
	Male	92 22.6%	24 11.8%	116 19.0%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	407 participants	204 participants	611 participants
	Hispanic or Latino	75 18.4%	46 22.5%	121 19.8%
	Not Hispanic or Latino	332 81.6%	158 77.5%	490 80.2%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	407 participants	204 participants	611 participants
	American Indian or Alaska Native	1 0.2%	0 0.0%	1 0.2%
	Asian	5 1.2%	6 2.9%	11 1.8%
	Native Hawaiian or Other Pacific Islander	3 0.7%	0 0.0%	3 0.5%
	Black or African American	80 19.7%	36 17.6%	116 19.0%
	White	307 75.4%	158 77.5%	465 76.1%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	11 2.7%	4 2.0%	15 2.5%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title		Semaglutide 2.4 mg	Placebo
Arm/Group Description:		Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.	Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Overall Number of Participants Analyzed		407	204
Mean (Standard Deviation); Unit of Measure: Percentage
In-trial observation period	Number Analyzed	373 participants	189 participants
		-16.5 (10.1)	-5.8 (7.7)
On-treatment observation period	Number Analyzed	334 participants	164 participants
		-17.6 (9.6)	-6.1 (7.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Semaglutide 2.4 mg, Placebo
	Comments	Treatment policy estimand
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<.0001
	Comments	[Not Specified]
	Method	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-10.27
	Confidence Interval	(2-Sided) 95%; -11.97 to -8.57
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Semaglutide 2.4 mg, Placebo
	Comments	Hypothetical estimand
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	MMRM (mixed model repeated measurement)
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-12.67
	Confidence Interval	(2-Sided) 95%; -14.34 to -11.00
	Estimation Comments	[Not Specified]

2. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title		Semaglutide 2.4 mg	Placebo
Arm/Group Description:		Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.	Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Overall Number of Participants Analyzed		407	204
Measure Type: Count of Participants; Unit of Measure: Participants
In-trial observation period	Number Analyzed	373 participants	189 participants
	Yes	323 86.6%	90 47.6%
	No	50 13.4%	99 52.4%
On-treatment observation period	Number Analyzed	334 participants	164 participants
	Yes	300 89.8%	82 50.0%
	No	34 10.2%	82 50.0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Semaglutide 2.4 mg, Placebo
	Comments	Treatment policy estimand
	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	6.11
	Confidence Interval	(2-Sided) 95%; 4.04 to 9.26
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Semaglutide 2.4 mg, Placebo
	Comments	Hypothetical estimand
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	[Not Specified]
	Method	MMRM (mixed model repeated measurement)
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	11.67
	Confidence Interval	(2-Sided) 95%; 7.64 to 17.81
	Estimation Comments	[Not Specified]

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.	Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Overall Number of Participants Analyzed	373	189
Measure Type: Count of Participants; Unit of Measure: Participants
Yes	281 75.3%	51 27.0%
No	92 24.7%	138 73.0%

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.	Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Overall Number of Participants Analyzed	373	189
Measure Type: Count of Participants; Unit of Measure: Participants
Yes	208 55.8%	25 13.2%
No	165 44.2%	164 86.8%

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.	Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Overall Number of Participants Analyzed	373	189
Measure Type: Count of Participants; Unit of Measure: Participants
Yes	133 35.7%	7 3.7%
No	240 64.3%	182 96.3%

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

8. Secondary Outcome

Title	Change in Short Form-36 (SF-36) - Physical Functioning Score
Description	SF-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ questionnaire measured eight domains of functional health and well-being as well as two component summary scores (physical component summary and mental component summary). The 0-100 scale scores from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. In the metric of norm-based scores, 50 and 10 corresponds to the mean and standard deviation respectively. Change from week 0 in the domain scores and component summary scores were evaluated at week 68. A positive change score indicates an improvement since baseline. These endpoints were evaluated based on the data from in-trial observation period which is the uninterrupted time interval from start of randomisation (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title		Semaglutide 2.4 mg	Placebo
Arm/Group Description:		Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.	Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Overall Number of Participants Analyzed		407	204
Mean (Standard Deviation); Unit of Measure: Score on a scale
Change in physical functioning score (SF-36)	Number Analyzed	364 participants	181 participants
		2.5 (5.7)	1.7 (5.7)
Change in SF-36: Role-Physical score	Number Analyzed	364 participants	181 participants
		1.6 (6.5)	1.5 (6.7)
Change in SF-36: Bodily Pain score	Number Analyzed	364 participants	181 participants
		1.3 (7.1)	0.6 (8.3)
Change in SF-36: General Health score	Number Analyzed	364 participants	181 participants
		3.4 (6.6)	1.9 (6.4)
Change in SF-36: Vitality score	Number Analyzed	364 participants	181 participants
		2.0 (8.2)	0.9 (7.8)
Change in SF-36: Social Functioning score	Number Analyzed	364 participants	181 participants
		0.1 (6.6)	-1.2 (8.0)
Change in SF-36: Mental Health score	Number Analyzed	364 participants	181 participants
		-0.5 (6.0)	-1.5 (7.1)
Change in SF-36: Physical component summary	Number Analyzed	364 participants	181 participants
		3.2 (6.0)	2.6 (6.5)
Change in SF-36: Mental component summary	Number Analyzed	364 participants	181 participants
		-0.9 (6.0)	-2.2 (8.0)
Change in SF-36: Role-Emotional score	Number Analyzed	364 participants	181 participants
		-0.6 (5.6)	-1.5 (7.7)

9. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

10. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

11. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

12. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

13. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

14. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

15. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

16. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

17. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

18. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

19. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

20. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

21. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

22. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

23. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

24. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.	Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
Overall Number of Participants Analyzed	364	181
Measure Type: Count of Participants; Unit of Measure: Participants
Yes (with threshold 4.3)	86 23.6%	36 19.9%
No (with threshold 4.3)	278 76.4%	145 80.1%
Yes (with threshold 3.7)	133 36.5%	51 28.2%
No (with threshold 3.7)	231 63.5%	130 71.8%

25. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

26. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

27. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

28. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

29. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

30. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

31. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

Adverse Events

Time Frame	week 0 to week 75 Results are based on the SAS which included all participants who received at least one dose of semaglutide or placebo.
Adverse Event Reporting Description	All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomised treatment and no later than the date of last dose + 7 weeks.
Arm/Group Title	Semaglutide 2.4 mg		Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of semaglutide using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to Intensive Behavioural Therapy (IBT), which involves physical activity and dietary intervention with the first 8 weeks of a low-calorie diet (LCD) followed by a strict hypo-caloric diet till the end of treatment.		Participants were to receive once-weekly s.c injection of matching semaglutide placebo using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing semaglutide placebo 1.0 mg/mL or 3.0 mg/mL or 3.2 mg/mL in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg, and 1.7 mg) every fourth week until a maintenance dose of 2.4 mg of semaglutide placebo was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to IBT, which involves physical activity and dietary intervention with the first 8 weeks of LCD followed by a strict hypo-caloric diet till the end of treatment.
All-Cause Mortality
	Semaglutide 2.4 mg		Placebo
	Affected / at Risk (%)		Affected / at Risk (%)
Total	0/407 (0.00%)		0/204 (0.00%)
Serious Adverse Events
	Semaglutide 2.4 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	37/407 (9.09%)		6/204 (2.94%)
Blood and lymphatic system disorders
Iron deficiency anaemia † 1	1/407 (0.25%)	1	0/204 (0.00%)	0
Ear and labyrinth disorders
Vertigo † 1	1/407 (0.25%)	1	0/204 (0.00%)	0
Gastrointestinal disorders
Abdominal pain † 1	1/407 (0.25%)	1	0/204 (0.00%)	0
Haemorrhoids thrombosed † 1	1/407 (0.25%)	1	0/204 (0.00%)	0
Incarcerated inguinal hernia † 1	0/407 (0.00%)	0	1/204 (0.49%)	1
Inguinal hernia † 1	0/407 (0.00%)	0	1/204 (0.49%)	1
Small intestinal obstruction † 1	0/407 (0.00%)	0	1/204 (0.49%)	1
General disorders
Non-cardiac chest pain † 1	1/407 (0.25%)	1	0/204 (0.00%)	0
Hepatobiliary disorders
Biliary dyskinesia † 1	1/407 (0.25%)	1	0/204 (0.00%)	0
Cholecystitis † 1	2/407 (0.49%)	2	0/204 (0.00%)	0
Cholecystitis acute † 1	3/407 (0.74%)	3	0/204 (0.00%)	0
Cholelithiasis † 1	7/407 (1.72%)	7	0/204 (0.00%)	0
Infections and infestations
Abdominal abscess † 1	1/407 (0.25%)	1	0/204 (0.00%)	0
Appendicitis † 1	3/407 (0.74%)	4	0/204 (0.00%)	0
Cellulitis † 1	1/407 (0.25%)	1	0/204 (0.00%)	0
Gastroenteritis viral † 1	1/407 (0.25%)	1	0/204 (0.00%)	0
Large intestine infection † 1	1/407 (0.25%)	1	0/204 (0.00%)	0
Pelvic inflammatory disease † 1	1/407 (0.25%)	1	0/204 (0.00%)	0
Pneumonia † 1	1/407 (0.25%)	1	0/204 (0.00%)	0
Sepsis † 1	1/407 (0.25%)	1	0/204 (0.00%)	0
Urinary tract infection † 1	1/407 (0.25%)	1	0/204 (0.00%)	0
Injury, poisoning and procedural complications
Hip fracture † 1	1/407 (0.25%)	1	0/204 (0.00%)	0
Joint dislocation † 1	1/407 (0.25%)	1	0/204 (0.00%)	0
Overdose † 1	1/407 (0.25%)	1	0/204 (0.00%)	0
Spinal compression fracture † 1	1/407 (0.25%)	1	0/204 (0.00%)	0
Upper limb fracture † 1	0/407 (0.00%)	0	1/204 (0.49%)	1
Metabolism and nutrition disorders
Hypokalaemia † 1	1/407 (0.25%)	1	0/204 (0.00%)	0
Obesity † 1	0/407 (0.00%)	0	1/204 (0.49%)	1
Musculoskeletal and connective tissue disorders
Back pain † 1	1/407 (0.25%)	1	0/204 (0.00%)	0
Cervical spinal stenosis † 1	2/407 (0.49%)	2	0/204 (0.00%)	0
Intervertebral disc protrusion † 1	1/407 (0.25%)	1	0/204 (0.00%)	0
Osteoarthritis † 1	3/407 (0.74%)	4	0/204 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer † 1	1/407 (0.25%)	1	0/204 (0.00%)	0
Castleman's disease † 1	0/407 (0.00%)	0	1/204 (0.49%)	1
Invasive lobular breast carcinoma † 1	0/407 (0.00%)	0	1/204 (0.49%)	1
Papillary thyroid cancer † 1	1/407 (0.25%)	1	0/204 (0.00%)	0
Uterine leiomyoma † 1	1/407 (0.25%)	1	0/204 (0.00%)	0
Nervous system disorders
Cerebral infarction † 1	1/407 (0.25%)	1	0/204 (0.00%)	0
Syncope † 1	1/407 (0.25%)	1	0/204 (0.00%)	0
Transient ischaemic attack † 1	1/407 (0.25%)	1	0/204 (0.00%)	0
Psychiatric disorders
Anxiety † 1	1/407 (0.25%)	1	0/204 (0.00%)	0
Renal and urinary disorders
Hydronephrosis † 1	1/407 (0.25%)	1	0/204 (0.00%)	0
Nephrolithiasis † 1	1/407 (0.25%)	1	0/204 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism † 1	1/407 (0.25%)	1	0/204 (0.00%)	0
Surgical and medical procedures
Neck dissection † 1	1/407 (0.25%)	1	0/204 (0.00%)	0
Vascular disorders
Deep vein thrombosis † 1	1/407 (0.25%)	1	0/204 (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 2.4 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	379/407 (93.12%)		177/204 (86.76%)
Gastrointestinal disorders
Abdominal distension † 1	41/407 (10.07%)	55	20/204 (9.80%)	28
Abdominal pain † 1	53/407 (13.02%)	75	10/204 (4.90%)	11
Abdominal pain upper † 1	33/407 (8.11%)	45	5/204 (2.45%)	5
Constipation † 1	150/407 (36.86%)	210	50/204 (24.51%)	62
Diarrhoea † 1	147/407 (36.12%)	307	45/204 (22.06%)	62
Dyspepsia † 1	36/407 (8.85%)	47	10/204 (4.90%)	15
Eructation † 1	36/407 (8.85%)	52	1/204 (0.49%)	1
Flatulence † 1	47/407 (11.55%)	62	23/204 (11.27%)	24
Gastrooesophageal reflux disease † 1	25/407 (6.14%)	32	4/204 (1.96%)	4
Nausea † 1	237/407 (58.23%)	511	45/204 (22.06%)	60
Vomiting † 1	111/407 (27.27%)	212	22/204 (10.78%)	25
General disorders
Fatigue † 1	52/407 (12.78%)	69	15/204 (7.35%)	19
Immune system disorders
Seasonal allergy † 1	12/407 (2.95%)	18	11/204 (5.39%)	14
Infections and infestations
Gastroenteritis † 1	28/407 (6.88%)	32	12/204 (5.88%)	19
Gastroenteritis viral † 1	41/407 (10.07%)	46	13/204 (6.37%)	13
Influenza † 1	27/407 (6.63%)	32	11/204 (5.39%)	11
Nasopharyngitis † 1	90/407 (22.11%)	128	49/204 (24.02%)	70
Sinusitis † 1	39/407 (9.58%)	51	26/204 (12.75%)	34
Upper respiratory tract infection † 1	85/407 (20.88%)	115	44/204 (21.57%)	65
Urinary tract infection † 1	41/407 (10.07%)	60	10/204 (4.90%)	11
Metabolism and nutrition disorders
Decreased appetite † 1	35/407 (8.60%)	36	7/204 (3.43%)	7
Musculoskeletal and connective tissue disorders
Arthralgia † 1	39/407 (9.58%)	54	19/204 (9.31%)	23
Back pain † 1	53/407 (13.02%)	67	22/204 (10.78%)	24
Pain in extremity † 1	17/407 (4.18%)	17	13/204 (6.37%)	14
Nervous system disorders
Dizziness † 1	52/407 (12.78%)	73	11/204 (5.39%)	14
Headache † 1	78/407 (19.16%)	123	20/204 (9.80%)	25
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain † 1	13/407 (3.19%)	17	12/204 (5.88%)	12
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 Reporting Anchor and Disclosure (1452)
• Organization: Novo Nordisk A/S
• Phone: (+1) 866-867-7178
• EMail: clinicaltrials@novonordisk.com

Publications of Results:

Wadden TA, Bailey TS, Billings LK, Davies M, Frias JP, Koroleva A, Lingvay I, O'Neil PM, Rubino DM, Skovgaard D, Wallenstein SOR, Garvey WT; STEP 3 Investigators. Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity: The STEP 3 Randomized Clinical Trial. JAMA. 2021 Apr 13;325(14):1403-1413. doi: 10.1001/jama.2021.1831.

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):

Perreault L, Davies M, Frias JP, Laursen PN, Lingvay I, Machineni S, Varbo A, Wilding JPH, Wallenstein SOR, le Roux CW. Changes in Glucose Metabolism and Glycemic Status With Once-Weekly Subcutaneous Semaglutide 2.4 mg Among Participants With Prediabetes in the STEP Program. Diabetes Care. 2022 Oct 1;45(10):2396-2405. doi: 10.2337/dc21-1785.

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: NCT03611582
• Other Study ID Numbers: NN9536-4375; U1111-1200-8199 ( Other Identifier: World Health Organization (WHO) )
• First Submitted: July 17, 2018
• First Posted: August 2, 2018
• Results First Submitted: June 16, 2021
• Results First Posted: July 9, 2021
• Last Update Posted: November 11, 2021