STEP 1: Research Study Investigating How Well Semaglutide Works in People Suffering From Overweight or Obesity (STEP 1)

• ClinicalTrials.gov Identifier: NCT03548935
• Recruitment Status: Completed
• First Posted: June 7, 2018
• Results First Posted: August 11, 2021
• Last Update Posted: November 19, 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: Metabolism and Nutrition Disorder; Overweight or Obesity
• Interventions: Drug: Semaglutide; Drug: Placebo (semaglutide)
• Enrollment: 1961

Participant Flow

Recruitment Details

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

Pre-assignment Details

The trial included an initial 16-week dose-escalation period and a 52-week dose maintenance period. Participants were randomized in 2:1 ratio either to receive semaglutide 2.4 mg or placebo. The treatment is an adjunct to reduced-calorie diet and increased physical activity.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Period Title: Overall Study
Started	1306	655
Full Analysis Set (FAS)	1306	655
Safety Analysis Set (SAS)	1306	655
Completed	1240	609
Not Completed	66	46
Reason Not Completed
Withdrawal by Subject	26	17
Lost to Follow-up	39	28
Death	1	1

Baseline Characteristics

Arm/Group Title		Semaglutide 2.4 mg	Placebo	Total
Arm/Group Description		Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Total of all reporting groups
Overall Number of Baseline Participants		1306	655	1961
Baseline Analysis Population Description		Full analysis set (FAS) included all randomized participants.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	1306 participants	655 participants	1961 participants
		46 (13)	47 (12)	46 (13)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1306 participants	655 participants	1961 participants
	Female	955 73.1%	498 76.0%	1453 74.1%
	Male	351 26.9%	157 24.0%	508 25.9%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1306 participants	655 participants	1961 participants
	Hispanic or Latino	150 11.5%	86 13.1%	236 12.0%
	Not Hispanic or Latino	1118 85.6%	551 84.1%	1669 85.1%
	Unknown or Not Reported	38 2.9%	18 2.7%	56 2.9%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1306 participants	655 participants	1961 participants
	American Indian or Alaska Native	17 1.3%	10 1.5%	27 1.4%
	Asian	181 13.9%	80 12.2%	261 13.3%
	Native Hawaiian or Other Pacific Islander	0 0.0%	2 0.3%	2 0.1%
	Black or African American	72 5.5%	39 6.0%	111 5.7%
	White	973 74.5%	499 76.2%	1472 75.1%
	More than one race	25 1.9%	8 1.2%	33 1.7%
	Unknown or Not Reported	38 2.9%	17 2.6%	55 2.8%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title		Semaglutide 2.4 mg	Placebo
Arm/Group Description:		Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed		1306	655
Mean (Standard Deviation); Unit of Measure: Percentage point
In-trial observation period	Number Analyzed	1212 participants	577 participants
		-15.6 (10.1)	-2.8 (6.5)
On-treatment observation period	Number Analyzed	1059 participants	499 participants
		-16.9 (9.4)	-3.1 (6.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Semaglutide 2.4 mg, Placebo
	Comments	Treatment policy estimand
	Type of Statistical Test	Superiority
	Comments	[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	-12.44
	Confidence Interval	(2-Sided) 95%; -13.37 to -11.51
	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	ANCOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-14.42
	Confidence Interval	(2-Sided) 95%; -15.29 to -13.55
	Estimation Comments	[Not Specified]

2. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title		Semaglutide 2.4 mg	Placebo
Arm/Group Description:		Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed		1306	655
Measure Type: Count of Participants; Unit of Measure: Participants
In-trial observation period	Number Analyzed	1212 participants	577 participants
	Yes	1047 86.4%	182 31.5%
	No	165 13.6%	395 68.5%
On-treatment observation period	Number Analyzed	1059 participants	499 participants
	Yes	978 92.4%	165 33.1%
	No	81 7.6%	334 66.9%

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	11.22
	Confidence Interval	(2-Sided) 95%; 8.88 to 14.19
	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	Regression, Logistic
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	37.03
	Confidence Interval	(2-Sided) 95%; 28.02 to 48.95
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Subjects Who Achieve 10 or More Percent Body Weight Reduction (Yes/no)
Description	Number of participants who achieved weight loss more than or equal to (≥) 10% at week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from date of randomization (week 0) to date of last contact with trial site (week 75).
Time Frame	Week 68

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	1212	577
Measure Type: Count of Participants; Unit of Measure: Participants
Yes	838 69.1%	69 12.0%
No	374 30.9%	508 88.0%

4. Secondary Outcome

Title	Participants Who Achieve 15 or More Percent Body Weight Reduction (Yes/no)
Description	Number of participants who achieved more than or equal to (≥) 15% weight loss at week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Week 68

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	1212	577
Measure Type: Count of Participants; Unit of Measure: Participants
Yes	612 50.5%	28 4.9%
No	600 49.5%	549 95.1%

5. Secondary Outcome

Title	Participants Who Achieve 20 or More Percent Body Weight Reduction (Yes/no)
Description	Number of participants who achieved more than or equal to (≥) 20% weight loss at week 68 is presented. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Week 68

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	1212	577
Measure Type: Count of Participants; Unit of Measure: Participants
Yes	388 32.0%	10 1.7%
No	824 68.0%	567 98.3%

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

8. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

9. Secondary Outcome

Title	Change in Impact of Weight on Quality of Life-Lite for Clinical Trial (IWQoL-Lite for CT) Score
Description	IWQoL-Lite for CT is a modified version of an instrument designed to assess weight-related quality of life. It is used to assess the impact of body weight changes on patients' physical and psychosocial functioning in three composite scores (physical function, physical and psychosocial) and a total score. The scores range between 0-100 where higher scores indicate a better quality of life. A positive change score indicates an improvement since baseline. These endpoints were evaluated based on the data from in-trial observation period which is the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

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

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

10. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

11. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

12. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

13. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

14. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

15. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

16. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

17. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

18. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

19. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

20. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

21. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

22. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

23. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

24. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

25. Secondary Outcome

Title	Change in Soluble Leptin Receptor (ng/mL) - Ratio to Baseline
Description	Change in soluble leptin receptor from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from start of randomization (week 0) to last trial-related subject-site contact (week 75).
Time Frame	Baseline (week 0) to week 68

Outcome Measure Data

Analysis Population Description

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

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

26. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

27. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

DEXA analysis set (DXA) includes participants in the sub-population of FAS that have had a DEXA scan performed at baseline. 'Overall Number of Participants Analyzed' = participants with available data.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	83	39
Mean (Standard Deviation); Unit of Measure: Percentage point
	-3.9 (5.4)	-0.3 (2.8)

28. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

DEXA analysis set (DXA) includes participants in the sub-population of FAS that have had a DEXA scan performed at baseline. 'Overall Number of Participants Analyzed' = participants with available data.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	83	39
Mean (Standard Deviation); Unit of Measure: Kilograms
	-9.3 (8.5)	-1.5 (5.1)

29. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

DEXA analysis set (DXA) includes participants in the sub-population of FAS that have had a DEXA scan performed at baseline. 'Overall Number of Participants Analyzed' = participants with available data.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	83	39
Mean (Standard Deviation); Unit of Measure: Percentage point
	3.4 (5.1)	0.2 (2.7)

30. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

DEXA analysis set (DXA) includes participants in the sub-population of FAS that have had a DEXA scan performed at baseline. 'Overall Number of Participants Analyzed' = participants with available data.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	83	39
Mean (Standard Deviation); Unit of Measure: Kilograms
	-5.8 (4.6)	-1.8 (2.5)

31. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

DEXA analysis set (DXA) includes participants in the sub-population of FAS that have had a DEXA scan performed at baseline. 'Overall Number of Participants Analyzed' = participants with available data.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	83	39
Mean (Standard Deviation); Unit of Measure: Percentage point
	-2.2 (4.4)	-0.1 (4.5)

32. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

DEXA analysis set (DXA) includes participants in the sub-population of FAS that have had a DEXA scan performed at baseline. 'Overall Number of Participants Analyzed' = participants with available data.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	83	39
Mean (Standard Deviation); Unit of Measure: Kilograms
	-0.4 (0.3)	-0.1 (0.3)

33. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

DEXA analysis set (DXA) includes participants in the sub-population of FAS that have had a DEXA scan performed at baseline. 'Overall Number of Participants Analyzed' = participants with available data.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	89	42
Mean (Standard Deviation); Unit of Measure: Percentage point
	-15.8 (11.1)	-3.4 (6.1)

34. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

DEXA analysis set (DXA) includes participants in the sub-population of FAS that have had a DEXA scan performed at baseline. 'Overall Number of Participants Analyzed' = participants with available data.

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	89	42
Mean (Standard Deviation); Unit of Measure: Kilograms
	-15.5 (11.4)	-3.2 (6.1)

35. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	1195	566
Measure Type: Count of Participants; Unit of Measure: Participants
Yes (with threshold 4.3)	318 26.6%	97 17.1%
No (with threshold 4.3)	877 73.4%	469 82.9%
Yes (with threshold 3.7)	478 40.0%	153 27.0%
No (with threshold 3.7)	717 60.0%	413 73.0%

36. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Semaglutide 2.4 mg	Placebo
Arm/Group Description:	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
Overall Number of Participants Analyzed	1193	566
Measure Type: Count of Participants; Unit of Measure: Participants
Yes (with threshold 20)	473 39.6%	145 25.6%
No (with threshold 20)	720 60.4%	421 74.4%
Yes (with threshold 14.6)	611 51.2%	186 32.9%
No (with threshold 14.6)	582 48.8%	380 67.1%

37. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

38. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

39. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

40. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

41. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

42. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

Adverse Events

Time Frame	week 0 to week 75 Results are based on the SAS which included all participants who received at least one dose of Semaglutide or placebo.
Adverse Event Reporting Description	All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks.
Arm/Group Title	Sema 2.4 mg		Placebo
Arm/Group Description	Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg Semaglutide once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.		Participants were to receive once-weekly subcutaneous (s.c) injection of 0.25 mg Semaglutide placebo administered using a PDS290 pre-filled pen-injector with a 3 mL cartridge containing Semaglutide placebo 1.0 mg/mL or 3.0 mg/mL and followed a fixed-dose escalation regimen, with dose increases every 4 weeks (to doses of 0.5, 1.0, 1.7 and 2.4 mg/week), aiming at reaching the maintenance dose of 2.4 mg Semaglutide placebo after 16 weeks. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 52 weeks until week 68. The treatment was an adjunct to a reduced-calorie diet and increased physical activity.
All-Cause Mortality
	Sema 2.4 mg		Placebo
	Affected / at Risk (%)		Affected / at Risk (%)
Total	1/1306 (0.08%)		1/655 (0.15%)
Serious Adverse Events
	Sema 2.4 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	128/1306 (9.80%)		42/655 (6.41%)
Blood and lymphatic system disorders
Anaemia † 1	2/1306 (0.15%)	2	0/655 (0.00%)	0
Splenic haemorrhage † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Cardiac disorders
Acute myocardial infarction † 1	2/1306 (0.15%)	2	1/655 (0.15%)	1
Angina pectoris † 1	0/1306 (0.00%)	0	1/655 (0.15%)	1
Angina unstable † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Atrial fibrillation † 1	2/1306 (0.15%)	4	1/655 (0.15%)	1
Atrial tachycardia † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Cardiomyopathy † 1	0/1306 (0.00%)	0	1/655 (0.15%)	1
Coronary artery stenosis † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Myocardial infarction † 1	0/1306 (0.00%)	0	2/655 (0.31%)	2
Myocarditis † 1	0/1306 (0.00%)	0	1/655 (0.15%)	1
Palpitations † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Ear and labyrinth disorders
Meniere's disease † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Vertigo † 1	3/1306 (0.23%)	3	0/655 (0.00%)	0
Eye disorders
Diplopia † 1	1/1306 (0.08%)	2	0/655 (0.00%)	0
Optic ischaemic neuropathy † 1	2/1306 (0.15%)	2	0/655 (0.00%)	0
Gastrointestinal disorders
Abdominal hernia † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Abdominal pain † 1	3/1306 (0.23%)	3	0/655 (0.00%)	0
Abdominal pain lower † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Anal fistula † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Colitis † 1	2/1306 (0.15%)	2	0/655 (0.00%)	0
Colitis ischaemic † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Constipation † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Diarrhoea † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Duodenal ulcer † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Enteritis † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Hiatus hernia † 1	2/1306 (0.15%)	2	0/655 (0.00%)	0
Large intestine perforation † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Nausea † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Oesophageal achalasia † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Pancreatitis acute † 1	2/1306 (0.15%)	2	0/655 (0.00%)	0
Volvulus † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Vomiting † 1	4/1306 (0.31%)	4	0/655 (0.00%)	0
General disorders
Chest pain † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Non-cardiac chest pain † 1	2/1306 (0.15%)	2	0/655 (0.00%)	0
Pyrexia † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Vascular stent occlusion † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Hepatobiliary disorders
Bile duct stone † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Cholecystitis † 1	4/1306 (0.31%)	4	0/655 (0.00%)	0
Cholecystitis acute † 1	3/1306 (0.23%)	3	0/655 (0.00%)	0
Cholelithiasis † 1	12/1306 (0.92%)	12	1/655 (0.15%)	1
Hypertransaminasaemia † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Immune system disorders
Hypersensitivity † 1	0/1306 (0.00%)	0	1/655 (0.15%)	1
Infections and infestations
Acute sinusitis † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Appendicitis † 1	5/1306 (0.38%)	5	1/655 (0.15%)	1
Appendicitis perforated † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Arthritis infective † 1	0/1306 (0.00%)	0	1/655 (0.15%)	1
Bacterial colitis † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Cellulitis † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Chronic sinusitis † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Cytomegalovirus infection † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Device related infection † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Empyema † 1	0/1306 (0.00%)	0	1/655 (0.15%)	1
Gastroenteritis † 1	5/1306 (0.38%)	5	0/655 (0.00%)	0
Gastroenteritis astroviral † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Hepatitis E † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Large intestine infection † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Meningitis viral † 1	0/1306 (0.00%)	0	1/655 (0.15%)	1
Neutropenic sepsis † 1	0/1306 (0.00%)	0	1/655 (0.15%)	1
Pneumonia † 1	0/1306 (0.00%)	0	2/655 (0.31%)	2
Pyelonephritis † 1	2/1306 (0.15%)	2	0/655 (0.00%)	0
Respiratory syncytial virus infection † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Respiratory tract infection † 1	0/1306 (0.00%)	0	1/655 (0.15%)	1
Septic shock † 1	0/1306 (0.00%)	0	1/655 (0.15%)	1
Sinusitis † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Staphylococcal infection † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Staphylococcal sepsis † 1	0/1306 (0.00%)	0	1/655 (0.15%)	1
Subcutaneous abscess † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Tonsillitis † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Toxoplasmosis † 1	0/1306 (0.00%)	0	1/655 (0.15%)	1
Urinary tract infection † 1	0/1306 (0.00%)	0	1/655 (0.15%)	1
Injury, poisoning and procedural complications
Ankle fracture † 1	1/1306 (0.08%)	1	1/655 (0.15%)	1
Femur fracture † 1	1/1306 (0.08%)	2	0/655 (0.00%)	0
Gun shot wound † 1	0/1306 (0.00%)	0	1/655 (0.15%)	1
Ligament rupture † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Meniscus injury † 1	1/1306 (0.08%)	1	1/655 (0.15%)	1
Post procedural haemorrhage † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Procedural haemorrhage † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Radius fracture † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Rib fracture † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Road traffic accident † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Subdural haematoma † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Thoracic vertebral fracture † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Tibia fracture † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Investigations
Lipase increased † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Weight increased † 1	0/1306 (0.00%)	0	1/655 (0.15%)	1
Metabolism and nutrition disorders
Gout † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Hypokalaemia † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Musculoskeletal and connective tissue disorders
Arthropathy † 1	0/1306 (0.00%)	0	1/655 (0.15%)	1
Back pain † 1	1/1306 (0.08%)	1	1/655 (0.15%)	1
Costochondritis † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Intervertebral disc degeneration † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Intervertebral disc protrusion † 1	1/1306 (0.08%)	1	1/655 (0.15%)	1
Muscular weakness † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Musculoskeletal chest pain † 1	0/1306 (0.00%)	0	1/655 (0.15%)	1
Musculoskeletal pain † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Myalgia intercostal † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Osteoarthritis † 1	3/1306 (0.23%)	3	2/655 (0.31%)	2
Rotator cuff syndrome † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cervix carcinoma stage 0 † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Gastrointestinal stromal tumour † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Glioblastoma † 1	0/1306 (0.00%)	0	1/655 (0.15%)	1
Hairy cell leukaemia † 1	0/1306 (0.00%)	0	1/655 (0.15%)	1
Intraductal proliferative breast lesion † 1	2/1306 (0.15%)	2	1/655 (0.15%)	1
Invasive ductal breast carcinoma † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Leiomyoma † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Ovarian adenoma † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Papillary thyroid cancer † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Prostate cancer † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Nervous system disorders
Aphasia † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Cerebral infarction † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Cranial nerve disorder † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Dizziness † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Headache † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Idiopathic intracranial hypertension † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Ischaemic stroke † 1	0/1306 (0.00%)	0	1/655 (0.15%)	1
Nerve compression † 1	1/1306 (0.08%)	1	1/655 (0.15%)	1
Peroneal nerve palsy † 1	0/1306 (0.00%)	0	1/655 (0.15%)	1
Psychogenic seizure † 1	0/1306 (0.00%)	0	1/655 (0.15%)	1
Vertigo CNS origin † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous † 1	2/1306 (0.15%)	2	0/655 (0.00%)	0
Ectopic pregnancy † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Psychiatric disorders
Acute stress disorder † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Anxiety † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Suicidal ideation † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Suicide attempt † 1	0/1306 (0.00%)	0	1/655 (0.15%)	1
Renal and urinary disorders
Calculus urinary † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Nephrolithiasis † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Reproductive system and breast disorders
Dysfunctional uterine bleeding † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Erectile dysfunction † 1	0/1306 (0.00%)	0	1/655 (0.15%)	1
Ovarian cyst † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Uterine haemorrhage † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure † 1	0/1306 (0.00%)	0	1/655 (0.15%)	1
Asthma † 1	0/1306 (0.00%)	0	2/655 (0.31%)	2
Nasal polyps † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Pleurisy † 1	0/1306 (0.00%)	0	1/655 (0.15%)	1
Pulmonary embolism † 1	2/1306 (0.15%)	2	2/655 (0.31%)	2
Tonsillar hypertrophy † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Skin and subcutaneous tissue disorders
Actinic keratosis † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Decubitus ulcer † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Hidradenitis † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Surgical and medical procedures
Abdominoplasty † 1	0/1306 (0.00%)	0	1/655 (0.15%)	1
Bone prosthesis insertion † 1	0/1306 (0.00%)	0	1/655 (0.15%)	1
Cholecystectomy † 1	1/1306 (0.08%)	1	1/655 (0.15%)	1
Gastric bypass † 1	1/1306 (0.08%)	1	1/655 (0.15%)	1
Hip surgery † 1	0/1306 (0.00%)	0	1/655 (0.15%)	1
Intervertebral disc operation † 1	1/1306 (0.08%)	1	0/655 (0.00%)	0
Vascular disorders
Deep vein thrombosis † 1	0/1306 (0.00%)	0	1/655 (0.15%)	1
Haematoma † 1	0/1306 (0.00%)	0	1/655 (0.15%)	1
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%
	Sema 2.4 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1052/1306 (80.55%)		447/655 (68.24%)
Gastrointestinal disorders
Abdominal distension † 1	96/1306 (7.35%)	135	31/655 (4.73%)	42
Abdominal pain † 1	127/1306 (9.72%)	172	36/655 (5.50%)	41
Abdominal pain upper † 1	125/1306 (9.57%)	176	35/655 (5.34%)	37
Constipation † 1	305/1306 (23.35%)	389	62/655 (9.47%)	73
Diarrhoea † 1	411/1306 (31.47%)	765	104/655 (15.88%)	138
Dyspepsia † 1	135/1306 (10.34%)	179	23/655 (3.51%)	30
Eructation † 1	112/1306 (8.58%)	139	3/655 (0.46%)	3
Gastrooesophageal reflux disease † 1	82/1306 (6.28%)	92	20/655 (3.05%)	21
Nausea † 1	576/1306 (44.10%)	1067	114/655 (17.40%)	146
Vomiting † 1	321/1306 (24.58%)	632	43/655 (6.56%)	52
General disorders
Fatigue † 1	104/1306 (7.96%)	120	28/655 (4.27%)	29
Infections and infestations
Gastroenteritis † 1	81/1306 (6.20%)	99	30/655 (4.58%)	38
Influenza † 1	89/1306 (6.81%)	112	63/655 (9.62%)	79
Nasopharyngitis † 1	281/1306 (21.52%)	480	133/655 (20.31%)	216
Sinusitis † 1	70/1306 (5.36%)	83	36/655 (5.50%)	40
Upper respiratory tract infection † 1	114/1306 (8.73%)	158	80/655 (12.21%)	116
Urinary tract infection † 1	68/1306 (5.21%)	83	28/655 (4.27%)	33
Metabolism and nutrition disorders
Decreased appetite † 1	124/1306 (9.49%)	139	22/655 (3.36%)	26
Musculoskeletal and connective tissue disorders
Arthralgia † 1	81/1306 (6.20%)	92	43/655 (6.56%)	47
Back pain † 1	106/1306 (8.12%)	120	53/655 (8.09%)	55
Nervous system disorders
Dizziness † 1	98/1306 (7.50%)	129	23/655 (3.51%)	35
Headache † 1	198/1306 (15.16%)	386	80/655 (12.21%)	104
Respiratory, thoracic and mediastinal disorders
Cough † 1	40/1306 (3.06%)	45	33/655 (5.04%)	35
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:

Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MTD, Wadden TA, Wharton S, Yokote K, Zeuthen N, Kushner RF; STEP 1 Study Group. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 Mar 18;384(11):989-1002. doi: 10.1056/NEJMoa2032183. Epub 2021 Feb 10.

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):

Kosiborod MN, Bhatta M, Davies M, Deanfield JE, Garvey WT, Khalid U, Kushner R, Rubino DM, Zeuthen N, Verma S. Semaglutide improves cardiometabolic risk factors in adults with overweight or obesity: STEP 1 and 4 exploratory analyses. Diabetes Obes Metab. 2023 Feb;25(2):468-478. doi: 10.1111/dom.14890. Epub 2022 Oct 28.

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.

Wilding JPH, Batterham RL, Davies M, Van Gaal LF, Kandler K, Konakli K, Lingvay I, McGowan BM, Oral TK, Rosenstock J, Wadden TA, Wharton S, Yokote K, Kushner RF; STEP 1 Study Group. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obes Metab. 2022 Aug;24(8):1553-1564. doi: 10.1111/dom.14725. Epub 2022 May 19.

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: NCT03548935
• Other Study ID Numbers: NN9536-4373; U1111-1200-8053 ( Other Identifier: World Health Organization (WHO) ); 2017-003436-36 ( Registry Identifier: European Medicines Agency (EudraCT) )
• First Submitted: May 25, 2018
• First Posted: June 7, 2018
• Results First Submitted: June 16, 2021
• Results First Posted: August 11, 2021
• Last Update Posted: November 19, 2021