Trial Outcomes & Findings for STEP 6: Research Study Investigating How Well Semaglutide Works in People Living With Overweight or Obesity (NCT NCT03811574)

NCT ID: NCT03811574

Last Updated: 2022-03-22

Results Overview

Change from baseline (week 0) in body weight for 'in-trial' observation period at week 68 is presented. In-trial observation period: the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact (week 75).

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 401 participants
• Primary outcome timeframe: Baseline (week 0), week 68
• Results posted on: 2022-03-22

Participant Flow

The trial was conducted at 28 sites in 2 countries as follows (all sites screened and randomized):Japan (22 sites) and South korea (6 sites).

The trial has a 68-week treatment period (12 weeks of dose escalation and 56 weeks of maintenance dose for 1.7 milligram (mg) once weekly arm and 16 weeks of dose escalation and 52 weeks of maintenance dose for 2.4 mg once weekly arm). Participants were randomised in 4:1:2:1 ratio to receive either semaglutide subcutaneously (s.c.) 2.4 mg once-weekly, semaglutide placebo once-weekly, semaglutide s.c. 1.7 mg once-weekly or semaglutide placebo once-weekly.

Participant milestones

Measure	Semaglutide 1.7 mg Participants were to receive once-weekly s.c. injection of 0.25 mg semaglutide administered using a PDS290 pre-filled pen-injector with a 3 milliliter (mL) cartridge containing semaglutide 1.0 milligram per milliliter (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 and 1.7 mg/week), aiming at reaching the maintenance dose of 1.7 mg once-weekly after 12 weeks. Treatment was continued on the maintenance dose of 1.7 mg once-weekly for an additional 56 weeks until week 68. The treatment was an adjunct to a reduced calorie diet and increased physical activity.	Semaglutide 2.4 mg Participants were to receive once-weekly 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 once-weekly 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.	Placebo Participants were to receive once-weekly s.c. injection of placebo matched to semaglutide for 68 weeks.
Overall Study STARTED	101	199	101
Overall Study Full Analysis Set (FAS)	101	199	101
Overall Study Safety Analysis Set (SAS)	100	199	101
Overall Study Treated	100	199	101
Overall Study COMPLETED	99	195	101
Overall Study NOT COMPLETED	2	4	0

Reasons for withdrawal

Measure	Semaglutide 1.7 mg Participants were to receive once-weekly s.c. injection of 0.25 mg semaglutide administered using a PDS290 pre-filled pen-injector with a 3 milliliter (mL) cartridge containing semaglutide 1.0 milligram per milliliter (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 and 1.7 mg/week), aiming at reaching the maintenance dose of 1.7 mg once-weekly after 12 weeks. Treatment was continued on the maintenance dose of 1.7 mg once-weekly for an additional 56 weeks until week 68. The treatment was an adjunct to a reduced calorie diet and increased physical activity.	Semaglutide 2.4 mg Participants were to receive once-weekly 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 once-weekly 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.	Placebo Participants were to receive once-weekly s.c. injection of placebo matched to semaglutide for 68 weeks.
Overall Study Withdrawal by Subject	2	4	0

Baseline Characteristics

STEP 6: Research Study Investigating How Well Semaglutide Works in People Living With Overweight or Obesity

Baseline characteristics by cohort

Measure	Semaglutide 2.4 mg n=199 Participants Participants were to receive once-weekly 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 once-weekly 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.	Placebo n=101 Participants Participants were to receive once-weekly s.c. injection of placebo matched to semaglutide for 68 weeks.	Semaglutide 1.7 mg n=101 Participants Participants were to receive once-weekly 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 and 1.7 mg/week), aiming at reaching the maintenance dose of 1.7 mg once-weekly after 12 weeks. Treatment was continued on the maintenance dose of 1.7 mg once-weekly for an additional 56 weeks until week 68. The treatment was an adjunct to a reduced calorie diet and increased physical activity.	Total n=401 Participants Total of all reporting groups
Age, Continuous	52 Years STANDARD_DEVIATION 12 • n=7 Participants	50 Years STANDARD_DEVIATION 9 • n=5 Participants	51 Years STANDARD_DEVIATION 10 • n=5 Participants	51 Years STANDARD_DEVIATION 11 • n=4 Participants
Sex: Female, Male Female	85 Participants n=7 Participants	26 Participants n=5 Participants	37 Participants n=5 Participants	148 Participants n=4 Participants
Sex: Female, Male Male	114 Participants n=7 Participants	75 Participants n=5 Participants	64 Participants n=5 Participants	253 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	199 Participants n=7 Participants	101 Participants n=5 Participants	101 Participants n=5 Participants	401 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	199 Participants n=7 Participants	101 Participants n=5 Participants	101 Participants n=5 Participants	401 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline (week 0), week 68

Population: FAS which comprised all randomised participants. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Change from baseline (week 0) in body weight for 'in-trial' observation period at week 68 is presented. In-trial observation period: the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact (week 75).

Outcome measures

Measure	Semaglutide 2.4 mg n=193 Participants Participants were to receive once-weekly 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 once-weekly 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.	Placebo n=100 Participants Participants were to receive once-weekly s.c. injection of placebo matched to semaglutide for 68 weeks.	Semaglutide 1.7 mg n=98 Participants 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 and 1.7 mg/week), aiming at reaching the maintenance dose of 1.7 mg once-weekly after 12 weeks. Treatment was continued on the maintenance dose of 1.7 mg once-weekly for an additional 56 weeks until week 68. The treatment was an adjunct to a reduced calorie diet and increased physical activity.
Change in Body Weight (%)	-13.4 Percentage change Standard Deviation 8.6	-1.9 Percentage change Standard Deviation 5.9	-9.9 Percentage change Standard Deviation 7.8

PRIMARY outcome

Timeframe: At week 68

Population: FAS which comprised all randomised participants. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Number of participants who achieved greater than or equal to (≥) 5% weight loss at week 68 for in-trial observation period is presented. In the reported data, 'Yes' infers the number of participants who have achieved ≥ 5% weight loss, whereas 'No' infers the number of participants who have not achieved ≥ 5% weight loss. In-trial observation period: the uninterrupted time interval from the start of randomisation (week 0) to last trial-related subject-site contact (week 75).

Outcome measures

Measure	Semaglutide 2.4 mg n=193 Participants Participants were to receive once-weekly 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 once-weekly 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.	Placebo n=100 Participants Participants were to receive once-weekly s.c. injection of placebo matched to semaglutide for 68 weeks.	Semaglutide 1.7 mg n=98 Participants 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 and 1.7 mg/week), aiming at reaching the maintenance dose of 1.7 mg once-weekly after 12 weeks. Treatment was continued on the maintenance dose of 1.7 mg once-weekly for an additional 56 weeks until week 68. The treatment was an adjunct to a reduced calorie diet and increased physical activity.
Number of Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 5% Yes	160 Participants	21 Participants	71 Participants
Number of Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 5% No	33 Participants	79 Participants	27 Participants

SECONDARY outcome

Timeframe: At week 68

Population: FAS which comprised all randomized participants. Overall number of participants analyzed = participants with available data.

Number of participants who achieved greater than or equal to (≥) 10% weight loss at week 68 is presented. In the reported data, 'Yes' infers the number of participants who have achieved ≥ 10% weight loss, whereas 'No' infers the number of participants who have not achieved ≥ 10% weight loss. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomisation to last trial-related subject-site contact.

Outcome measures

Measure	Semaglutide 2.4 mg n=193 Participants Participants were to receive once-weekly 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 once-weekly 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.	Placebo n=100 Participants Participants were to receive once-weekly s.c. injection of placebo matched to semaglutide for 68 weeks.	Semaglutide 1.7 mg n=98 Participants 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 and 1.7 mg/week), aiming at reaching the maintenance dose of 1.7 mg once-weekly after 12 weeks. Treatment was continued on the maintenance dose of 1.7 mg once-weekly for an additional 56 weeks until week 68. The treatment was an adjunct to a reduced calorie diet and increased physical activity.
Number of Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 10% Yes	117 Participants	5 Participants	41 Participants
Number of Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 10% No	76 Participants	95 Participants	57 Participants

SECONDARY outcome

Timeframe: At week 68

Population: FAS which comprised all randomised participants. Overall number of participants analyzed = participants with available data.

Number of participants who achieved greater than or equal to (≥) 15% weight loss at week 68 is presented. In the reported data, 'Yes' infers the number of participants who have achieved ≥ 15% weight loss, whereas 'No' infers the number of participants who have not achieved ≥ 15% weight loss. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomization to last trial-related subject-site contact.

Outcome measures

Measure	Semaglutide 2.4 mg n=193 Participants Participants were to receive once-weekly 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 once-weekly 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.	Placebo n=100 Participants Participants were to receive once-weekly s.c. injection of placebo matched to semaglutide for 68 weeks.	Semaglutide 1.7 mg n=98 Participants 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 and 1.7 mg/week), aiming at reaching the maintenance dose of 1.7 mg once-weekly after 12 weeks. Treatment was continued on the maintenance dose of 1.7 mg once-weekly for an additional 56 weeks until week 68. The treatment was an adjunct to a reduced calorie diet and increased physical activity.
Number of Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 15% Yes	79 Participants	3 Participants	24 Participants
Number of Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 15% No	114 Participants	97 Participants	74 Participants

SECONDARY outcome

Timeframe: At week 68

Population: FAS which comprised all randomised participants. Overall number of participants analyzed = participants with available data.

Number of participants who achieved greater than or equal to (≥) 20% weight loss at week 68 is presented. In the reported data, 'Yes' infers the number of participants who have achieved ≥ 20% weight loss, whereas 'No' infers the number of participants who have not achieved ≥ 20% weight loss. The endpoint was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from the start of randomisation to last trial-related subject-site contact.

Outcome measures

Measure	Semaglutide 2.4 mg n=193 Participants Participants were to receive once-weekly 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 once-weekly 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.	Placebo n=100 Participants Participants were to receive once-weekly s.c. injection of placebo matched to semaglutide for 68 weeks.	Semaglutide 1.7 mg n=98 Participants 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 and 1.7 mg/week), aiming at reaching the maintenance dose of 1.7 mg once-weekly after 12 weeks. Treatment was continued on the maintenance dose of 1.7 mg once-weekly for an additional 56 weeks until week 68. The treatment was an adjunct to a reduced calorie diet and increased physical activity.
Number of Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 20% Yes	38 Participants	2 Participants	11 Participants
Number of Participants Who Achieve (Yes/no): Body Weight Reduction More Than or Equal to 20% No	155 Participants	98 Participants	87 Participants

SECONDARY outcome

Timeframe: Baseline (week 0) to week 68

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

Change in waist circumference measured midway between the lower rib margin and the iliac crest 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 the start of randomisation to last trial-related subject-site contact.

Outcome measures

Measure	Semaglutide 2.4 mg n=193 Participants Participants were to receive once-weekly 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 once-weekly 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.	Placebo n=100 Participants Participants were to receive once-weekly s.c. injection of placebo matched to semaglutide for 68 weeks.	Semaglutide 1.7 mg n=98 Participants 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 and 1.7 mg/week), aiming at reaching the maintenance dose of 1.7 mg once-weekly after 12 weeks. Treatment was continued on the maintenance dose of 1.7 mg once-weekly for an additional 56 weeks until week 68. The treatment was an adjunct to a reduced calorie diet and increased physical activity.
Change in Waist Circumference Measured Midway Between the Lower Rib Margin and the Iliac Crest	-11.2 Centimeter (cm) Standard Deviation 7.5	-1.8 Centimeter (cm) Standard Deviation 5.9	-7.8 Centimeter (cm) Standard Deviation 6.9

SECONDARY outcome

Timeframe: Baseline (week 0) to week 68

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

Change in Waist circumference measured according to the JASSO guideline 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 the start of randomisation to last trial-related subject-site contact.

Outcome measures

Measure	Semaglutide 2.4 mg n=193 Participants Participants were to receive once-weekly 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 once-weekly 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.	Placebo n=100 Participants Participants were to receive once-weekly s.c. injection of placebo matched to semaglutide for 68 weeks.	Semaglutide 1.7 mg n=98 Participants 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 and 1.7 mg/week), aiming at reaching the maintenance dose of 1.7 mg once-weekly after 12 weeks. Treatment was continued on the maintenance dose of 1.7 mg once-weekly for an additional 56 weeks until week 68. The treatment was an adjunct to a reduced calorie diet and increased physical activity.
Change in Waist Circumference Measured According to the JASSO (Japan Society for the Study of Obesity) Guideline	-10.2 Centimeter (cm) Standard Deviation 6.8	-1.9 Centimeter (cm) Standard Deviation 5.3	-7.6 Centimeter (cm) Standard Deviation 5.7

SECONDARY outcome

Timeframe: Baseline (week 0) to week 68

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

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 the start of randomisation to last trial-related subject-site contact.

Outcome measures

Measure	Semaglutide 2.4 mg n=193 Participants Participants were to receive once-weekly 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 once-weekly 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.	Placebo n=100 Participants Participants were to receive once-weekly s.c. injection of placebo matched to semaglutide for 68 weeks.	Semaglutide 1.7 mg n=98 Participants 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 and 1.7 mg/week), aiming at reaching the maintenance dose of 1.7 mg once-weekly after 12 weeks. Treatment was continued on the maintenance dose of 1.7 mg once-weekly for an additional 56 weeks until week 68. The treatment was an adjunct to a reduced calorie diet and increased physical activity.
Change in Body Weight (Kg)	-11.3 Kilogram (kg) Standard Deviation 7.3	-1.7 Kilogram (kg) Standard Deviation 5.6	-8.3 Kilogram (kg) Standard Deviation 6.1

SECONDARY outcome

Timeframe: Baseline (week 0) to week 68

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

Change in BMI 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 the start of randomisation to last trial-related subject-site contact.

Outcome measures

Measure	Semaglutide 2.4 mg n=193 Participants Participants were to receive once-weekly 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 once-weekly 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.	Placebo n=100 Participants Participants were to receive once-weekly s.c. injection of placebo matched to semaglutide for 68 weeks.	Semaglutide 1.7 mg n=98 Participants 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 and 1.7 mg/week), aiming at reaching the maintenance dose of 1.7 mg once-weekly after 12 weeks. Treatment was continued on the maintenance dose of 1.7 mg once-weekly for an additional 56 weeks until week 68. The treatment was an adjunct to a reduced calorie diet and increased physical activity.
Change in Body Mass Index (BMI)	-4.3 Kilogram per square meter (kg/m^2) Standard Deviation 2.8	-0.6 Kilogram per square meter (kg/m^2) Standard Deviation 2.0	-3.1 Kilogram per square meter (kg/m^2) Standard Deviation 2.4

SECONDARY outcome

Timeframe: Baseline (week 0) to week 68

Population: CT scan subpopulation included all randomised participants who had a CT scan assessment. 'Overall Number of Participants Analyzed' = participants with available data.

Change in VFA 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 the start of randomisation to last trial-related subject-site contact.

Outcome measures

Measure	Semaglutide 2.4 mg n=86 Participants Participants were to receive once-weekly 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 once-weekly 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.	Placebo n=43 Participants Participants were to receive once-weekly s.c. injection of placebo matched to semaglutide for 68 weeks.	Semaglutide 1.7 mg n=45 Participants 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 and 1.7 mg/week), aiming at reaching the maintenance dose of 1.7 mg once-weekly after 12 weeks. Treatment was continued on the maintenance dose of 1.7 mg once-weekly for an additional 56 weeks until week 68. The treatment was an adjunct to a reduced calorie diet and increased physical activity.
Change in Visceral Fat Area (VFA) (%)	-41.0 Percentage change Standard Deviation 23.3	-7.1 Percentage change Standard Deviation 19.5	-22.3 Percentage change Standard Deviation 31.3

SECONDARY outcome

Timeframe: Baseline (week 0) to week 68

Population: CT scan subpopulation included all randomised participants who had a CT scan assessment. 'Overall Number of Participants Analyzed' = participants with available data.

Change in VFA 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 the start of randomisation to last trial-related subject-site contact.

Outcome measures

Measure	Semaglutide 2.4 mg n=86 Participants Participants were to receive once-weekly 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 once-weekly 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.	Placebo n=43 Participants Participants were to receive once-weekly s.c. injection of placebo matched to semaglutide for 68 weeks.	Semaglutide 1.7 mg n=45 Participants 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 and 1.7 mg/week), aiming at reaching the maintenance dose of 1.7 mg once-weekly after 12 weeks. Treatment was continued on the maintenance dose of 1.7 mg once-weekly for an additional 56 weeks until week 68. The treatment was an adjunct to a reduced calorie diet and increased physical activity.
Change in Visceral Fat Area (VFA) Centimeter Square (cm^2)	-67.4 centimeter square (cm^2) Standard Deviation 43.0	-13.8 centimeter square (cm^2) Standard Deviation 38.6	-41.7 centimeter square (cm^2) Standard Deviation 47.0

SECONDARY outcome

Timeframe: Baseline (week 0) to week 68

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

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 the start of randomisation to last trial-related subject-site contact.

Outcome measures

Measure	Semaglutide 2.4 mg n=193 Participants Participants were to receive once-weekly 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 once-weekly 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.	Placebo n=100 Participants Participants were to receive once-weekly s.c. injection of placebo matched to semaglutide for 68 weeks.	Semaglutide 1.7 mg n=98 Participants 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 and 1.7 mg/week), aiming at reaching the maintenance dose of 1.7 mg once-weekly after 12 weeks. Treatment was continued on the maintenance dose of 1.7 mg once-weekly for an additional 56 weeks until week 68. The treatment was an adjunct to a reduced calorie diet and increased physical activity.
Change in HbA1c (%)	-1.0 Percentage of HbA1c Standard Deviation 1.0	0.0 Percentage of HbA1c Standard Deviation 0.8	-0.9 Percentage of HbA1c Standard Deviation 0.8

SECONDARY outcome

Timeframe: Baseline (week 0) to week 68

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

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 the start of randomisation to last trial-related subject-site contact.

Outcome measures

Measure	Semaglutide 2.4 mg n=193 Participants Participants were to receive once-weekly 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 once-weekly 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.	Placebo n=100 Participants Participants were to receive once-weekly s.c. injection of placebo matched to semaglutide for 68 weeks.	Semaglutide 1.7 mg n=98 Participants 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 and 1.7 mg/week), aiming at reaching the maintenance dose of 1.7 mg once-weekly after 12 weeks. Treatment was continued on the maintenance dose of 1.7 mg once-weekly for an additional 56 weeks until week 68. The treatment was an adjunct to a reduced calorie diet and increased physical activity.
Change in HbA1c (mmol/Mol)	-10.6 millimoles per mole (mmol/mol) Standard Deviation 10.4	-0.1 millimoles per mole (mmol/mol) Standard Deviation 8.3	-9.9 millimoles per mole (mmol/mol) Standard Deviation 8.9

SECONDARY outcome

Timeframe: Baseline (week 0) to week 68

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

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 the start of randomization to last trial-related subject-site contact.

Outcome measures

Measure	Semaglutide 2.4 mg n=192 Participants Participants were to receive once-weekly 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 once-weekly 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.	Placebo n=98 Participants Participants were to receive once-weekly s.c. injection of placebo matched to semaglutide for 68 weeks.	Semaglutide 1.7 mg n=97 Participants 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 and 1.7 mg/week), aiming at reaching the maintenance dose of 1.7 mg once-weekly after 12 weeks. Treatment was continued on the maintenance dose of 1.7 mg once-weekly for an additional 56 weeks until week 68. The treatment was an adjunct to a reduced calorie diet and increased physical activity.
Change in Fasting Plasma Glucose	-19.3 Milligrams per deciliter (mg/dL) Standard Deviation 22.6	1.7 Milligrams per deciliter (mg/dL) Standard Deviation 26.1	-18.3 Milligrams per deciliter (mg/dL) Standard Deviation 21.9

SECONDARY outcome

Timeframe: Baseline (week 0) to week 68

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

Change in fasting serum insulin measured as milli-international units per milliliter (mIU/mL) 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 the start of randomisation to last trial-related subject-site contact.

Outcome measures

Measure	Semaglutide 2.4 mg n=190 Participants Participants were to receive once-weekly 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 once-weekly 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.	Placebo n=98 Participants Participants were to receive once-weekly s.c. injection of placebo matched to semaglutide for 68 weeks.	Semaglutide 1.7 mg n=97 Participants 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 and 1.7 mg/week), aiming at reaching the maintenance dose of 1.7 mg once-weekly after 12 weeks. Treatment was continued on the maintenance dose of 1.7 mg once-weekly for an additional 56 weeks until week 68. The treatment was an adjunct to a reduced calorie diet and increased physical activity.
Change in Fasting Serum Insulin-ratio to Baseline	0.71 Ratio of fasting serum insulin Geometric Coefficient of Variation 57.7	0.89 Ratio of fasting serum insulin Geometric Coefficient of Variation 49.4	0.85 Ratio of fasting serum insulin Geometric Coefficient of Variation 65

SECONDARY outcome

Timeframe: Baseline (week 0) to week 68

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

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 the start of randomisation to last trial-related subject-site contact.

Outcome measures

Measure	Semaglutide 2.4 mg n=193 Participants Participants were to receive once-weekly 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 once-weekly 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.	Placebo n=100 Participants Participants were to receive once-weekly s.c. injection of placebo matched to semaglutide for 68 weeks.	Semaglutide 1.7 mg n=98 Participants 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 and 1.7 mg/week), aiming at reaching the maintenance dose of 1.7 mg once-weekly after 12 weeks. Treatment was continued on the maintenance dose of 1.7 mg once-weekly for an additional 56 weeks until week 68. The treatment was an adjunct to a reduced calorie diet and increased physical activity.
Change in Systolic Blood Pressure	-11 millimeters of mercury (mmHg) Standard Deviation 15	-5 millimeters of mercury (mmHg) Standard Deviation 15	-12 millimeters of mercury (mmHg) Standard Deviation 13

SECONDARY outcome

Timeframe: Baseline (week 0) to week 68

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

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 the start of randomisation to last trial-related subject-site contact.

Outcome measures

Measure	Semaglutide 2.4 mg n=193 Participants Participants were to receive once-weekly 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 once-weekly 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.	Placebo n=100 Participants Participants were to receive once-weekly s.c. injection of placebo matched to semaglutide for 68 weeks.	Semaglutide 1.7 mg n=98 Participants 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 and 1.7 mg/week), aiming at reaching the maintenance dose of 1.7 mg once-weekly after 12 weeks. Treatment was continued on the maintenance dose of 1.7 mg once-weekly for an additional 56 weeks until week 68. The treatment was an adjunct to a reduced calorie diet and increased physical activity.
Change in Diastolic Blood Pressure	-5 mmHg Standard Deviation 10	-3 mmHg Standard Deviation 9	-5 mmHg Standard Deviation 10

SECONDARY outcome

Timeframe: Baseline (week 0) to week 68

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

Change in total cholesterol measured as milligrams per deciliter (mg/dL) 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 the start of randomisation to last trial-related subject-site contact.

Outcome measures

Measure	Semaglutide 2.4 mg n=193 Participants Participants were to receive once-weekly 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 once-weekly 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.	Placebo n=100 Participants Participants were to receive once-weekly s.c. injection of placebo matched to semaglutide for 68 weeks.	Semaglutide 1.7 mg n=98 Participants 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 and 1.7 mg/week), aiming at reaching the maintenance dose of 1.7 mg once-weekly after 12 weeks. Treatment was continued on the maintenance dose of 1.7 mg once-weekly for an additional 56 weeks until week 68. The treatment was an adjunct to a reduced calorie diet and increased physical activity.
Change in Total Cholesterol-ratio to Baseline	0.91 Ratio of total cholesterol Geometric Coefficient of Variation 13.3	1.00 Ratio of total cholesterol Geometric Coefficient of Variation 12.7	0.93 Ratio of total cholesterol Geometric Coefficient of Variation 16.5

SECONDARY outcome

Timeframe: Baseline (week 0) to week 68

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

Change in HDL measured as milligrams per deciliter (mg/dL) 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 the start of randomisation to last trial-related subject-site contact.

Outcome measures

Measure	Semaglutide 2.4 mg n=193 Participants Participants were to receive once-weekly 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 once-weekly 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.	Placebo n=100 Participants Participants were to receive once-weekly s.c. injection of placebo matched to semaglutide for 68 weeks.	Semaglutide 1.7 mg n=98 Participants 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 and 1.7 mg/week), aiming at reaching the maintenance dose of 1.7 mg once-weekly after 12 weeks. Treatment was continued on the maintenance dose of 1.7 mg once-weekly for an additional 56 weeks until week 68. The treatment was an adjunct to a reduced calorie diet and increased physical activity.
Change in High-density Lipoproteins (HDL)-Ratio to Baseline	1.08 Ratio of high-density lipoproteins Geometric Coefficient of Variation 13.7	1.06 Ratio of high-density lipoproteins Geometric Coefficient of Variation 12.1	1.06 Ratio of high-density lipoproteins Geometric Coefficient of Variation 17.3

SECONDARY outcome

Timeframe: Baseline (week 0) to week 68

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

Change in LDL measured as milligrams per deciliter (mg/dL) 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 the start of randomization to last trial-related subject-site contact.

Outcome measures

Measure	Semaglutide 2.4 mg n=193 Participants Participants were to receive once-weekly 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 once-weekly 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.	Placebo n=99 Participants Participants were to receive once-weekly s.c. injection of placebo matched to semaglutide for 68 weeks.	Semaglutide 1.7 mg n=98 Participants 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 and 1.7 mg/week), aiming at reaching the maintenance dose of 1.7 mg once-weekly after 12 weeks. Treatment was continued on the maintenance dose of 1.7 mg once-weekly for an additional 56 weeks until week 68. The treatment was an adjunct to a reduced calorie diet and increased physical activity.
Change in Low-density Lipoproteins (LDL)-Ratio to Baseline	0.86 Ratio of low-density lipoproteins Geometric Coefficient of Variation 23.5	0.95 Ratio of low-density lipoproteins Geometric Coefficient of Variation 21.1	0.90 Ratio of low-density lipoproteins Geometric Coefficient of Variation 25.2

SECONDARY outcome

Timeframe: Baseline (week 0) to week 68

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

Change in VLDL measured as milligrams per deciliter (mg/dL) 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 the start of randomization to last trial-related subject-site contact.

Outcome measures

Measure	Semaglutide 2.4 mg n=193 Participants Participants were to receive once-weekly 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 once-weekly 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.	Placebo n=99 Participants Participants were to receive once-weekly s.c. injection of placebo matched to semaglutide for 68 weeks.	Semaglutide 1.7 mg n=98 Participants 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 and 1.7 mg/week), aiming at reaching the maintenance dose of 1.7 mg once-weekly after 12 weeks. Treatment was continued on the maintenance dose of 1.7 mg once-weekly for an additional 56 weeks until week 68. The treatment was an adjunct to a reduced calorie diet and increased physical activity.
Change in Very Low-density Lipoproteins (VLDL)-Ratio to Baseline	0.79 Ratio of very low-density lipoproteins Geometric Coefficient of Variation 43.2	1.05 Ratio of very low-density lipoproteins Geometric Coefficient of Variation 41.2	0.79 Ratio of very low-density lipoproteins Geometric Coefficient of Variation 43.2

SECONDARY outcome

Timeframe: Baseline (week 0) to week 68

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

Change in free fatty acids measured as milligrams per deciliter (mg/dL) 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 the start of randomisation to last trial-related subject-site contact.

Outcome measures

Measure	Semaglutide 2.4 mg n=190 Participants Participants were to receive once-weekly 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 once-weekly 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.	Placebo n=98 Participants Participants were to receive once-weekly s.c. injection of placebo matched to semaglutide for 68 weeks.	Semaglutide 1.7 mg n=97 Participants 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 and 1.7 mg/week), aiming at reaching the maintenance dose of 1.7 mg once-weekly after 12 weeks. Treatment was continued on the maintenance dose of 1.7 mg once-weekly for an additional 56 weeks until week 68. The treatment was an adjunct to a reduced calorie diet and increased physical activity.
Change in Free Fatty Acids-ratio to Baseline	0.96 Ratio of free fatty acids Geometric Coefficient of Variation 59.1	1.28 Ratio of free fatty acids Geometric Coefficient of Variation 52.6	1.04 Ratio of free fatty acids Geometric Coefficient of Variation 57.7

SECONDARY outcome

Timeframe: Baseline (week 0) to week 68

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

Change in triglycerides measured as milligrams per deciliter (mg/dL) 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 the start of randomisation to last trial-related subject-site contact.

Outcome measures

Measure	Semaglutide 2.4 mg n=193 Participants Participants were to receive once-weekly 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 once-weekly 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.	Placebo n=99 Participants Participants were to receive once-weekly s.c. injection of placebo matched to semaglutide for 68 weeks.	Semaglutide 1.7 mg n=98 Participants 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 and 1.7 mg/week), aiming at reaching the maintenance dose of 1.7 mg once-weekly after 12 weeks. Treatment was continued on the maintenance dose of 1.7 mg once-weekly for an additional 56 weeks until week 68. The treatment was an adjunct to a reduced calorie diet and increased physical activity.
Change in Triglycerides-ratio to Baseline	0.79 Ratio of triglycerides Geometric Coefficient of Variation 43.8	1.05 Ratio of triglycerides Geometric Coefficient of Variation 41.0	0.78 Ratio of triglycerides Geometric Coefficient of Variation 49.8

SECONDARY outcome

Timeframe: Baseline (week 0) to week 68

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

Change in hsCRP measured in milligram per ilitre (mg/L) 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 the start of randomisation to last trial-related subject-site contact.

Outcome measures

Measure	Semaglutide 2.4 mg n=193 Participants Participants were to receive once-weekly 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 once-weekly 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.	Placebo n=100 Participants Participants were to receive once-weekly s.c. injection of placebo matched to semaglutide for 68 weeks.	Semaglutide 1.7 mg n=98 Participants 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 and 1.7 mg/week), aiming at reaching the maintenance dose of 1.7 mg once-weekly after 12 weeks. Treatment was continued on the maintenance dose of 1.7 mg once-weekly for an additional 56 weeks until week 68. The treatment was an adjunct to a reduced calorie diet and increased physical activity.
Change in High Sensitivity C-reactive Protein (hsCRP)-Ratio to Baseline	0.39 Ratio of hsCRP Geometric Coefficient of Variation 119.3	0.92 Ratio of hsCRP Geometric Coefficient of Variation 123	0.64 Ratio of hsCRP Geometric Coefficient of Variation 218.3

SECONDARY outcome

Timeframe: Baseline (week 0) to week 68

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

Change in plasminogen activator inhibitor-1 (PAI-1) activity measured in arbritary units per milliliter (AU/ml) 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 the start of randomisation to last trial-related subject-site contact.

Outcome measures

Measure	Semaglutide 2.4 mg n=190 Participants Participants were to receive once-weekly 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 once-weekly 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.	Placebo n=98 Participants Participants were to receive once-weekly s.c. injection of placebo matched to semaglutide for 68 weeks.	Semaglutide 1.7 mg n=97 Participants 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 and 1.7 mg/week), aiming at reaching the maintenance dose of 1.7 mg once-weekly after 12 weeks. Treatment was continued on the maintenance dose of 1.7 mg once-weekly for an additional 56 weeks until week 68. The treatment was an adjunct to a reduced calorie diet and increased physical activity.
Change in Plasminogen Activator Inhibitor-1 Activity-ratio to Baseline	0.68 Ratio of PAI-1 activity Geometric Coefficient of Variation 62	1 Ratio of PAI-1 activity Geometric Coefficient of Variation 51.8	0.83 Ratio of PAI-1 activity Geometric Coefficient of Variation 75.8

SECONDARY outcome

Timeframe: Baseline (week 0) to week 68

Population: FAS included all randomised participants. Overall Number of Participants Analyzed = number of participants with available data.

SF-36 is a 36-item patient-reported survey of patient health that measures participant's overall health-related quality of life (HRQoL). SF-36v2™ questionnaire measured eight domains of functional health and well-being as well as 2 component summary scores (physical component summary and mental component summary). This endpoint shows results for all the domains. The 0-100 scale scores from SF-36 were converted to norm-based scores to enable a direct interpretation in relation to distribution of scores in the 2009 U.S. general population. In metric of norm-based scores, 50 and 10 corresponds to mean and standard deviation respectively. Change from week 0 in 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 data from in-trial observation period which is uninterrupted time interval from randomisation to last contact with trial site.

Outcome measures

Measure	Semaglutide 2.4 mg n=192 Participants Participants were to receive once-weekly 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 once-weekly 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.	Placebo n=100 Participants Participants were to receive once-weekly s.c. injection of placebo matched to semaglutide for 68 weeks.	Semaglutide 1.7 mg n=98 Participants 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 and 1.7 mg/week), aiming at reaching the maintenance dose of 1.7 mg once-weekly after 12 weeks. Treatment was continued on the maintenance dose of 1.7 mg once-weekly for an additional 56 weeks until week 68. The treatment was an adjunct to a reduced calorie diet and increased physical activity.
Change in Short Form 36 v2.0 Acute (SF-36) Score Change in SF-36:Physical functioning score	1.0 Score on a scale Standard Deviation 3.7	-0.5 Score on a scale Standard Deviation 3.9	0.0 Score on a scale Standard Deviation 5.7
Change in Short Form 36 v2.0 Acute (SF-36) Score Change in SF-36: Role-Physical score	-0.2 Score on a scale Standard Deviation 4.7	0.3 Score on a scale Standard Deviation 5.8	-1.6 Score on a scale Standard Deviation 5.2
Change in Short Form 36 v2.0 Acute (SF-36) Score Change in SF-36: Bodily Pain score	-1.1 Score on a scale Standard Deviation 7.5	-0.2 Score on a scale Standard Deviation 8.8	-1.8 Score on a scale Standard Deviation 9.2
Change in Short Form 36 v2.0 Acute (SF-36) Score Change in SF-36: General Health score	0.4 Score on a scale Standard Deviation 5.8	-0.6 Score on a scale Standard Deviation 5.6	-1.4 Score on a scale Standard Deviation 5.4
Change in Short Form 36 v2.0 Acute (SF-36) Score Change in SF-36: Vitality score	-1.5 Score on a scale Standard Deviation 6.8	-0.9 Score on a scale Standard Deviation 7.4	-2.4 Score on a scale Standard Deviation 7.8
Change in Short Form 36 v2.0 Acute (SF-36) Score Change in SF-36: Social Functioning score	-0.9 Score on a scale Standard Deviation 6.2	0.3 Score on a scale Standard Deviation 5.6	-0.8 Score on a scale Standard Deviation 3.8
Change in Short Form 36 v2.0 Acute (SF-36) Score Change in SF-36: Role-Emotional score	-1.1 Score on a scale Standard Deviation 5.5	-0.9 Score on a scale Standard Deviation 4.1	-1.6 Score on a scale Standard Deviation 5.6
Change in Short Form 36 v2.0 Acute (SF-36) Score Change in SF-36: Mental Health score	-1.5 Score on a scale Standard Deviation 6.7	-1.2 Score on a scale Standard Deviation 5.2	-1.9 Score on a scale Standard Deviation 7.2
Change in Short Form 36 v2.0 Acute (SF-36) Score Change in SF-36: Physical component summary	0.7 Score on a scale Standard Deviation 4.4	0.1 Score on a scale Standard Deviation 5.3	-0.8 Score on a scale Standard Deviation 6.0
Change in Short Form 36 v2.0 Acute (SF-36) Score Change in SF-36: Mental component summary	-1.9 Score on a scale Standard Deviation 6.4	-1.0 Score on a scale Standard Deviation 4.7	-2.0 Score on a scale Standard Deviation 6.4

SECONDARY outcome

Timeframe: Baseline (week 0) to week 68

Population: FAS included all randomised participants. Overall Number of Participants Analyzed = number of participants with available data.

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

Outcome measures

Measure	Semaglutide 2.4 mg n=192 Participants Participants were to receive once-weekly 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 once-weekly 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.	Placebo n=100 Participants Participants were to receive once-weekly s.c. injection of placebo matched to semaglutide for 68 weeks.	Semaglutide 1.7 mg n=98 Participants 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 and 1.7 mg/week), aiming at reaching the maintenance dose of 1.7 mg once-weekly after 12 weeks. Treatment was continued on the maintenance dose of 1.7 mg once-weekly for an additional 56 weeks until week 68. The treatment was an adjunct to a reduced calorie diet and increased physical activity.
Change in Impact of Weight on Quality of Life-lite for Clinical Trials (IWQOL-Lite for CT) Score Physical function score	4.9 Score on a scale Standard Deviation 15.1	0.5 Score on a scale Standard Deviation 12.7	2.6 Score on a scale Standard Deviation 16.3
Change in Impact of Weight on Quality of Life-lite for Clinical Trials (IWQOL-Lite for CT) Score Physical	4.2 Score on a scale Standard Deviation 14.4	-0.8 Score on a scale Standard Deviation 11.3	1.9 Score on a scale Standard Deviation 14.3
Change in Impact of Weight on Quality of Life-lite for Clinical Trials (IWQOL-Lite for CT) Score Psychosocial	5.2 Score on a scale Standard Deviation 12.7	-0.3 Score on a scale Standard Deviation 12.1	4.4 Score on a scale Standard Deviation 11.9
Change in Impact of Weight on Quality of Life-lite for Clinical Trials (IWQOL-Lite for CT) Score Total	4.8 Score on a scale Standard Deviation 11.8	-0.5 Score on a scale Standard Deviation 10.3	3.5 Score on a scale Standard Deviation 11.0

SECONDARY outcome

Timeframe: At week 68

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

The number of participants experiencing a meaningful within participant improvement in SF-36 Physical function after 68 weeks was determined based on 3.7 threshold. The threshold of 3.7 is specific for overweight or obese population included in the study and calculated using patient global rating anchor questionnaires to reflect participants' own perspective based on Food and Drug Administration (FDA) recommendations. In the reported data, "Yes" infers the number of participants who have achieved an improvement in score greater than or equal to the threshold and "No" infers number of participants who have not achieved an improvement in score greater than or equal to the threshold. The endpoint was evaluated based on in-trial observation period which is the uninterrupted time interval from randomisation to last contact with trial site.

Outcome measures

Measure	Semaglutide 2.4 mg n=192 Participants Participants were to receive once-weekly 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 once-weekly 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.	Placebo n=100 Participants Participants were to receive once-weekly s.c. injection of placebo matched to semaglutide for 68 weeks.	Semaglutide 1.7 mg n=98 Participants 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 and 1.7 mg/week), aiming at reaching the maintenance dose of 1.7 mg once-weekly after 12 weeks. Treatment was continued on the maintenance dose of 1.7 mg once-weekly for an additional 56 weeks until week 68. The treatment was an adjunct to a reduced calorie diet and increased physical activity.
Number of Participants Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score Yes	43 Participants	13 Participants	19 Participants
Number of Participants Who Achieve (Yes/no): Responder Definition Value for SF-36 Physical Functioning Score No	149 Participants	87 Participants	79 Participants

SECONDARY outcome

Timeframe: At week 68

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

The number of participants experiencing a meaningful within participant improvement in IWQOL-Lite-CT physical function after 68 weeks was determined based on thresholds of 14.6. 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 in-trial observation period which is the uninterrupted time interval from randomisation to last contact with trial site.

Outcome measures

Measure	Semaglutide 2.4 mg n=192 Participants Participants were to receive once-weekly 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 once-weekly 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.	Placebo n=100 Participants Participants were to receive once-weekly s.c. injection of placebo matched to semaglutide for 68 weeks.	Semaglutide 1.7 mg n=98 Participants 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 and 1.7 mg/week), aiming at reaching the maintenance dose of 1.7 mg once-weekly after 12 weeks. Treatment was continued on the maintenance dose of 1.7 mg once-weekly for an additional 56 weeks until week 68. The treatment was an adjunct to a reduced calorie diet and increased physical activity.
Number of Participants Who Achieve (Yes/no): Responder Definition Value for IWQoL-Lite for CT Physical Function (5-items) Score Yes	49 Participants	11 Participants	19 Participants
Number of Participants Who Achieve (Yes/no): Responder Definition Value for IWQoL-Lite for CT Physical Function (5-items) Score No	143 Participants	89 Participants	79 Participants

SECONDARY outcome

Timeframe: At week 68

Population: FAS included all randomised participants. Overall Number of Participants Analyzed = participants with type 2 diabetes at screening with available data.

Number of participants who achieved HbA1c <7% (53 mmol/mol) at week 68 is presented. In the reported data, "Yes" infers the number of participants who have achieved HbA1c values less than the 7% and "No" infers the number of participants who have not achieved HbA1c values less than the 7%. The endpoint was evaluated based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation to last trial-related subject-site contact.

Outcome measures

Measure	Semaglutide 2.4 mg n=49 Participants Participants were to receive once-weekly 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 once-weekly 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.	Placebo n=25 Participants Participants were to receive once-weekly s.c. injection of placebo matched to semaglutide for 68 weeks.	Semaglutide 1.7 mg n=25 Participants 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 and 1.7 mg/week), aiming at reaching the maintenance dose of 1.7 mg once-weekly after 12 weeks. Treatment was continued on the maintenance dose of 1.7 mg once-weekly for an additional 56 weeks until week 68. The treatment was an adjunct to a reduced calorie diet and increased physical activity.
Number of Participants Who Achieved (Yes/no): HbA1c <7.0% (53 mmol/Mol) Yes	43 Participants	1 Participants	24 Participants
Number of Participants Who Achieved (Yes/no): HbA1c <7.0% (53 mmol/Mol) No	6 Participants	24 Participants	1 Participants

SECONDARY outcome

Timeframe: At week 68

Population: FAS included all randomised participants. Overall Number of Participants Analyzed = participants with type 2 diabetes at screening with available data.

Number of participants who achieved HbA1c ≤6.5% (48 mmol/mol) at week 68 is presented. In the reported data, "Yes" infers the number of participants who have achieved HbA1c values less than or equal to 6.5% and "No" infers the number of participants who have not achieved HbA1c values less than or equal to 6.5%. The endpoint was evaluated based on the data from in-trial observation period which was defined as the uninterrupted time interval from the start of randomisation to last trial-related subject-site contact.

Outcome measures

Measure	Semaglutide 2.4 mg n=49 Participants Participants were to receive once-weekly 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 once-weekly 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.	Placebo n=25 Participants Participants were to receive once-weekly s.c. injection of placebo matched to semaglutide for 68 weeks.	Semaglutide 1.7 mg n=25 Participants 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 and 1.7 mg/week), aiming at reaching the maintenance dose of 1.7 mg once-weekly after 12 weeks. Treatment was continued on the maintenance dose of 1.7 mg once-weekly for an additional 56 weeks until week 68. The treatment was an adjunct to a reduced calorie diet and increased physical activity.
Number of Participants Who Achieved (Yes/no): HbA1c ≤6.5% (48 mmol/Mol) Yes	40 Participants	1 Participants	22 Participants
Number of Participants Who Achieved (Yes/no): HbA1c ≤6.5% (48 mmol/Mol) No	9 Participants	24 Participants	3 Participants

SECONDARY outcome

Timeframe: Week 0 to week 75

Population: Safety analysis set (SAS) included all randomised participants exposed to at least one dose of randomised treatment.

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 with onset during the on-treatment observation period. On-treatment observation period: the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 7 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses.

Outcome measures

Measure	Semaglutide 2.4 mg n=199 Participants Participants were to receive once-weekly 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 once-weekly 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.	Placebo n=101 Participants Participants were to receive once-weekly s.c. injection of placebo matched to semaglutide for 68 weeks.	Semaglutide 1.7 mg n=100 Participants 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 and 1.7 mg/week), aiming at reaching the maintenance dose of 1.7 mg once-weekly after 12 weeks. Treatment was continued on the maintenance dose of 1.7 mg once-weekly for an additional 56 weeks until week 68. The treatment was an adjunct to a reduced calorie diet and increased physical activity.
Number of Treatment-emergent AEs	834 Events	235 Events	483 Events

SECONDARY outcome

Timeframe: Week 0 to week 75

Population: Safety analysis set (SAS) included all randomised participants exposed to at least one dose of randomised treatment.

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. SAE results occurred from week 0 to week 75 is presented based on the on-treatment observation, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 7 week follow-up period and excluding any off-treatment time intervals. Off-treatment time interval: time period with at least two consecutive missed doses.

Outcome measures

Measure	Semaglutide 2.4 mg n=199 Participants Participants were to receive once-weekly 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 once-weekly 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.	Placebo n=101 Participants Participants were to receive once-weekly s.c. injection of placebo matched to semaglutide for 68 weeks.	Semaglutide 1.7 mg n=100 Participants 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 and 1.7 mg/week), aiming at reaching the maintenance dose of 1.7 mg once-weekly after 12 weeks. Treatment was continued on the maintenance dose of 1.7 mg once-weekly for an additional 56 weeks until week 68. The treatment was an adjunct to a reduced calorie diet and increased physical activity.
Number of Serious Adverse Events	12 Events	7 Events	10 Events

SECONDARY outcome

Timeframe: Week 0 to week 75

Population: Safety analysis set (SAS) included all randomised participants exposed to at least one dose of randomised treatment. Overall number of participants analyzed = participants with type 2 diabetes at screening.

Hypoglycaemic episodes with onset during on-treatment observation period were considered treatment-emergent. Number of treatment emergent severe or BG confirmed symptomatic hypoglycaemia episodes with onset during on-treatment observation period were presented. Severe hypoglycaemia: episode requiring assistance of another person to administer carbohydrate, glucagon or take other corrective actions. plasma glucose (PG) concentrations may not be available during an event, but neurological recovery following return of PG to normal is considered sufficient evidence that event was induced by low PG concentration. BG confirmed symptomatic hypoglycaemia: episode that is BG confirmed by PG value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. On-treatment observation period is interval from date of first trial product administration (week 0) to date of last trial product administration (week 68) plus 7-week follow-up period and excluding any off-treatment time intervals.

Outcome measures

Measure	Semaglutide 2.4 mg n=49 Participants Participants were to receive once-weekly 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 once-weekly 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.	Placebo n=25 Participants Participants were to receive once-weekly s.c. injection of placebo matched to semaglutide for 68 weeks.	Semaglutide 1.7 mg n=25 Participants 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 and 1.7 mg/week), aiming at reaching the maintenance dose of 1.7 mg once-weekly after 12 weeks. Treatment was continued on the maintenance dose of 1.7 mg once-weekly for an additional 56 weeks until week 68. The treatment was an adjunct to a reduced calorie diet and increased physical activity.
Number of Treatment Emergent Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemia Episodes	0 Episodes	0 Episodes	0 Episodes

SECONDARY outcome

Timeframe: Baseline (week 0) to week 68

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

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, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 7 week follow-up period and excluding any off-treatment time intervals.

Outcome measures

Measure	Semaglutide 2.4 mg n=186 Participants Participants were to receive once-weekly 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 once-weekly 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.	Placebo n=98 Participants Participants were to receive once-weekly s.c. injection of placebo matched to semaglutide for 68 weeks.	Semaglutide 1.7 mg n=93 Participants 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 and 1.7 mg/week), aiming at reaching the maintenance dose of 1.7 mg once-weekly after 12 weeks. Treatment was continued on the maintenance dose of 1.7 mg once-weekly for an additional 56 weeks until week 68. The treatment was an adjunct to a reduced calorie diet and increased physical activity.
Change in Pulse	4 Beats/minute Standard Deviation 9	2 Beats/minute Standard Deviation 10	6 Beats/minute Standard Deviation 10

SECONDARY outcome

Timeframe: Baseline (week 0) to week 68

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

Change in amylase measured in units/liter (U/L) from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 7 week follow-up period and excluding any off-treatment time intervals.

Outcome measures

Measure	Semaglutide 2.4 mg n=186 Participants Participants were to receive once-weekly 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 once-weekly 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.	Placebo n=98 Participants Participants were to receive once-weekly s.c. injection of placebo matched to semaglutide for 68 weeks.	Semaglutide 1.7 mg n=93 Participants 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 and 1.7 mg/week), aiming at reaching the maintenance dose of 1.7 mg once-weekly after 12 weeks. Treatment was continued on the maintenance dose of 1.7 mg once-weekly for an additional 56 weeks until week 68. The treatment was an adjunct to a reduced calorie diet and increased physical activity.
Change in Amylase: Ratio to Baseline	1.08 Ratio of amylase Geometric Coefficient of Variation 23.2	0.93 Ratio of amylase Geometric Coefficient of Variation 25.1	1.09 Ratio of amylase Geometric Coefficient of Variation 20.9

SECONDARY outcome

Timeframe: Baseline (week 0) to week 68

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

Change in lipase measured in units/litre (U/L) from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 7 week follow-up period and excluding any off-treatment time intervals.

Outcome measures

Measure	Semaglutide 2.4 mg n=186 Participants Participants were to receive once-weekly 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 once-weekly 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.	Placebo n=98 Participants Participants were to receive once-weekly s.c. injection of placebo matched to semaglutide for 68 weeks.	Semaglutide 1.7 mg n=93 Participants 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 and 1.7 mg/week), aiming at reaching the maintenance dose of 1.7 mg once-weekly after 12 weeks. Treatment was continued on the maintenance dose of 1.7 mg once-weekly for an additional 56 weeks until week 68. The treatment was an adjunct to a reduced calorie diet and increased physical activity.
Change in Lipase: Ratio to Baseline	1.56 Ratio of lipase Geometric Coefficient of Variation 45.4	0.96 Ratio of lipase Geometric Coefficient of Variation 40.5	1.56 Ratio of lipase Geometric Coefficient of Variation 39.8

SECONDARY outcome

Timeframe: Baseline (week 0) to week 68

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

Change in calcitonin measured in nanogram/litre (ng/L) from baseline (week 0) to week 68 is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 7 week follow-up period and excluding any off-treatment time intervals.

Outcome measures

Measure	Semaglutide 2.4 mg n=186 Participants Participants were to receive once-weekly 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 once-weekly 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.	Placebo n=98 Participants Participants were to receive once-weekly s.c. injection of placebo matched to semaglutide for 68 weeks.	Semaglutide 1.7 mg n=93 Participants 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 and 1.7 mg/week), aiming at reaching the maintenance dose of 1.7 mg once-weekly after 12 weeks. Treatment was continued on the maintenance dose of 1.7 mg once-weekly for an additional 56 weeks until week 68. The treatment was an adjunct to a reduced calorie diet and increased physical activity.
Change in Calcitonin: Ratio to Baseline	0.95 Ratio of calcitonin Geometric Coefficient of Variation 34.6	0.94 Ratio of calcitonin Geometric Coefficient of Variation 30.6	0.98 Ratio of calcitonin Geometric Coefficient of Variation 32.4

SECONDARY outcome

Timeframe: Baseline (week 0) to week 68

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

Change in QTCF Interval from baseline (week 0) to week 68 is presented. The endpoint was evaluated based on the data from on-treatment observation period, which was defined as the interval from the date of first trial product administration (week 0) to the date of last trial product administration (week 68) plus a 7 week follow-up period and excluding any off-treatment time intervals.

Outcome measures

Measure	Semaglutide 2.4 mg n=186 Participants Participants were to receive once-weekly 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 once-weekly 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.	Placebo n=96 Participants Participants were to receive once-weekly s.c. injection of placebo matched to semaglutide for 68 weeks.	Semaglutide 1.7 mg n=92 Participants 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 and 1.7 mg/week), aiming at reaching the maintenance dose of 1.7 mg once-weekly after 12 weeks. Treatment was continued on the maintenance dose of 1.7 mg once-weekly for an additional 56 weeks until week 68. The treatment was an adjunct to a reduced calorie diet and increased physical activity.
Change in QTCF Interval	-2.5 millisecond (msec) Standard Deviation 15.2	5.6 millisecond (msec) Standard Deviation 14.1	-2.2 millisecond (msec) Standard Deviation 17.8

Adverse Events

Semaglutide 1.7 mg

Serious events: 7 serious events

Other events: 73 other events

Deaths: 0 deaths

Semaglutide 2.4 mg

Serious events: 10 serious events

Other events: 142 other events

Deaths: 0 deaths

Placebo

Serious events: 7 serious events

Other events: 49 other events

Deaths: 0 deaths

Serious adverse events

Measure	Semaglutide 1.7 mg n=100 participants at risk 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 and 1.7 mg/week), aiming at reaching the maintenance dose of 1.7 mg once-weekly after 12 weeks. Treatment was continued on the maintenance dose of 1.7 mg once-weekly for an additional 56 weeks until week 68. The treatment was an adjunct to a reduced calorie diet and increased physical activity.	Semaglutide 2.4 mg n=199 participants at risk Participants were to receive once-weekly 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 once-weekly 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.	Placebo n=101 participants at risk Participants were to receive once-weekly s.c. injection of placebo matched to semaglutide for 68 weeks.
Injury, poisoning and procedural complications Muscle strain	1.0% 1/100 • Number of events 2 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.00% 0/199 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.00% 0/101 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.
Cardiac disorders Acute myocardial infarction	0.00% 0/100 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.50% 1/199 • Number of events 1 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.00% 0/101 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.
Cardiac disorders Atrial fibrillation	0.00% 0/100 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.00% 0/199 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.99% 1/101 • Number of events 1 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bile duct adenocarcinoma	1.0% 1/100 • Number of events 1 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.00% 0/199 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.00% 0/101 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.
Nervous system disorders Carpal tunnel syndrome	0.00% 0/100 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.50% 1/199 • Number of events 1 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.00% 0/101 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.
Hepatobiliary disorders Cholelithiasis	0.00% 0/100 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	1.0% 2/199 • Number of events 2 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.00% 0/101 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Clear cell renal cell carcinoma	1.0% 1/100 • Number of events 1 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.00% 0/199 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.00% 0/101 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.
Gastrointestinal disorders Colitis ischaemic	0.00% 0/100 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.50% 1/199 • Number of events 1 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.00% 0/101 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.
Congenital, familial and genetic disorders Diverticulitis Meckel's	0.00% 0/100 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.50% 1/199 • Number of events 1 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.00% 0/101 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.
Nervous system disorders Dizziness	1.0% 1/100 • Number of events 1 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.00% 0/199 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.00% 0/101 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.
Reproductive system and breast disorders Endometrial hyperplasia	1.0% 1/100 • Number of events 1 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.00% 0/199 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.00% 0/101 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.
Infections and infestations Infectious mononucleosis	1.0% 1/100 • Number of events 1 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.00% 0/199 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.00% 0/101 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.
Gastrointestinal disorders Intestinal obstruction	0.00% 0/100 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.00% 0/199 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.99% 1/101 • Number of events 1 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.
Gastrointestinal disorders Large intestine polyp	0.00% 0/100 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.50% 1/199 • Number of events 1 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.00% 0/101 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.
Injury, poisoning and procedural complications Ligament sprain	1.0% 1/100 • Number of events 1 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.00% 0/199 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.00% 0/101 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.00% 0/100 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.00% 0/199 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.99% 1/101 • Number of events 1 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.
Blood and lymphatic system disorders Lymphadenitis	1.0% 1/100 • Number of events 1 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.00% 0/199 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.00% 0/101 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.
Infections and infestations Pyelonephritis	0.00% 0/100 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.50% 1/199 • Number of events 1 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.00% 0/101 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.
Infections and infestations Pyelonephritis acute	0.00% 0/100 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.50% 1/199 • Number of events 1 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.00% 0/101 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.
Injury, poisoning and procedural complications Radius fracture	0.00% 0/100 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.00% 0/199 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.99% 1/101 • Number of events 1 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.
Musculoskeletal and connective tissue disorders Rhabdomyolysis	0.00% 0/100 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.50% 1/199 • Number of events 1 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.00% 0/101 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.
Eye disorders Rhegmatogenous retinal detachment	0.00% 0/100 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.00% 0/199 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.99% 1/101 • Number of events 1 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.
Injury, poisoning and procedural complications Road traffic accident	1.0% 1/100 • Number of events 1 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.00% 0/199 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.00% 0/101 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.
Injury, poisoning and procedural complications Subdural haematoma	0.00% 0/100 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.00% 0/199 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.99% 1/101 • Number of events 1 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.
Injury, poisoning and procedural complications Tendon rupture	0.00% 0/100 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.50% 1/199 • Number of events 1 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.00% 0/101 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.
Renal and urinary disorders Ureterolithiasis	0.00% 0/100 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.50% 1/199 • Number of events 1 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.99% 1/101 • Number of events 1 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.

Other adverse events

Measure	Semaglutide 1.7 mg n=100 participants at risk 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 and 1.7 mg/week), aiming at reaching the maintenance dose of 1.7 mg once-weekly after 12 weeks. Treatment was continued on the maintenance dose of 1.7 mg once-weekly for an additional 56 weeks until week 68. The treatment was an adjunct to a reduced calorie diet and increased physical activity.	Semaglutide 2.4 mg n=199 participants at risk Participants were to receive once-weekly 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 once-weekly 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.	Placebo n=101 participants at risk Participants were to receive once-weekly s.c. injection of placebo matched to semaglutide for 68 weeks.
Gastrointestinal disorders Abdominal discomfort	11.0% 11/100 • Number of events 12 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	6.0% 12/199 • Number of events 16 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.99% 1/101 • Number of events 1 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.
Gastrointestinal disorders Abdominal distension	7.0% 7/100 • Number of events 8 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	3.5% 7/199 • Number of events 8 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	2.0% 2/101 • Number of events 3 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.
Gastrointestinal disorders Abdominal pain	3.0% 3/100 • Number of events 4 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	6.0% 12/199 • Number of events 16 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.00% 0/101 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.
Gastrointestinal disorders Abdominal pain upper	3.0% 3/100 • Number of events 5 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	5.0% 10/199 • Number of events 13 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.99% 1/101 • Number of events 1 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.
Musculoskeletal and connective tissue disorders Arthralgia	9.0% 9/100 • Number of events 10 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	2.5% 5/199 • Number of events 5 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	5.9% 6/101 • Number of events 9 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.
Musculoskeletal and connective tissue disorders Back pain	8.0% 8/100 • Number of events 12 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	9.5% 19/199 • Number of events 20 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	8.9% 9/101 • Number of events 11 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.
Gastrointestinal disorders Constipation	19.0% 19/100 • Number of events 22 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	26.1% 52/199 • Number of events 60 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	3.0% 3/101 • Number of events 3 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.
Metabolism and nutrition disorders Decreased appetite	5.0% 5/100 • Number of events 5 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	6.5% 13/199 • Number of events 13 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.00% 0/101 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.
Gastrointestinal disorders Dental caries	4.0% 4/100 • Number of events 4 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	5.5% 11/199 • Number of events 12 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	5.0% 5/101 • Number of events 5 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.
Gastrointestinal disorders Diarrhoea	22.0% 22/100 • Number of events 59 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	16.1% 32/199 • Number of events 52 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	5.9% 6/101 • Number of events 6 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.
Nervous system disorders Dizziness	2.0% 2/100 • Number of events 4 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	7.0% 14/199 • Number of events 19 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.00% 0/101 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.
Gastrointestinal disorders Dyspepsia	6.0% 6/100 • Number of events 17 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	4.5% 9/199 • Number of events 14 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.99% 1/101 • Number of events 4 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.
Infections and infestations Gastroenteritis	7.0% 7/100 • Number of events 8 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	5.5% 11/199 • Number of events 13 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	0.99% 1/101 • Number of events 1 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.
Nervous system disorders Headache	2.0% 2/100 • Number of events 2 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	5.0% 10/199 • Number of events 12 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	3.0% 3/101 • Number of events 3 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.
Infections and infestations Nasopharyngitis	24.0% 24/100 • Number of events 36 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	26.6% 53/199 • Number of events 81 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	17.8% 18/101 • Number of events 24 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.
Gastrointestinal disorders Nausea	18.0% 18/100 • Number of events 27 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	17.6% 35/199 • Number of events 66 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	4.0% 4/101 • Number of events 4 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract inflammation	5.0% 5/100 • Number of events 6 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	5.5% 11/199 • Number of events 13 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	8.9% 9/101 • Number of events 13 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.
Gastrointestinal disorders Vomiting	10.0% 10/100 • Number of events 34 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	8.5% 17/199 • Number of events 29 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.	2.0% 2/101 • Number of events 2 • Week 0 to week 75. All presented AEs are treatment-emergent (i.e., TEAEs). Adverse events were defined as "treatment-emergent" (TEAE), if the onset of the event occurs in the on-treatment period. Results are based on the SAS which included all randomised participants exposed to at least one dose of randomised treatment.

Additional Information

Clinical Transparency Anchor and Disclosure (1452)

Novo Nordisk A/S

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Email: clinicaltrials@novonordisk.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
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Restriction type: OTHER