Trial Outcomes & Findings for Two-year Research Study Investigating How Well Semaglutide Works in People Suffering From Overweight or Obesity (NCT NCT03693430)

NCT ID: NCT03693430

Last Updated: 2023-07-06

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 304 participants
• Primary outcome timeframe: From Baseline (Week 0) to Week 104
• Results posted on: 2023-07-06

Participant Flow

The trial was conducted at 41 sites in 5 countries as follows: Canada (9 sites), Hungary (6 sites), Italy (5 sites), Spain (6 sites), and United States (15 sites).

Participants were randomized in a 1:1 manner to receive treatment with semaglutide 2.4 milligram (mg) or placebo once weekly as an adjunct to a reduced-calorie diet and increased physical activity. The trial has a 104 weeks treatment period (16 weeks of dose escalation period and 88 weeks of maintenance dose).

Participant milestones

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

Reasons for withdrawal

Measure	Semaglutide 2.4 mg Participants received once-weekly subcutaneous (s.c) injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Placebo Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Overall Study Lost to Follow-up	3	14
Overall Study Death	1	0
Overall Study Withdrawal by Subject	0	4

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Semaglutide 2.4 mg n=152 Participants Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Placebo n=152 Participants Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.	Total n=304 Participants Total of all reporting groups
Age, Continuous	47 years STANDARD_DEVIATION 12 • n=5 Participants	47 years STANDARD_DEVIATION 10 • n=7 Participants	47 years STANDARD_DEVIATION 11 • n=5 Participants
Sex: Female, Male Female	123 Participants n=5 Participants	113 Participants n=7 Participants	236 Participants n=5 Participants
Sex: Female, Male Male	29 Participants n=5 Participants	39 Participants n=7 Participants	68 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	18 Participants n=5 Participants	21 Participants n=7 Participants	39 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	134 Participants n=5 Participants	131 Participants n=7 Participants	265 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized White	141 Participants n=5 Participants	142 Participants n=7 Participants	283 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	7 Participants n=5 Participants	5 Participants n=7 Participants	12 Participants n=5 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized Asian	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: From Baseline (Week 0) to Week 104

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

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

Outcome measures

Measure	Semaglutide 2.4 mg n=144 Participants Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Placebo n=128 Participants Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Percentage Change From Baseline (Week 0) to Week 104 in Body Weight In-trial observation period	-15.9 percentage change Standard Deviation 12.3	-1.9 percentage change Standard Deviation 8.9
Percentage Change From Baseline (Week 0) to Week 104 in Body Weight On-treatment observation period	-17.3 percentage change Standard Deviation 11.9	-2.0 percentage change Standard Deviation 8.6

PRIMARY outcome

Timeframe: At Week 104

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

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

Outcome measures

Measure	Semaglutide 2.4 mg n=144 Participants Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Placebo n=128 Participants Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Number of Participants Who Achieved (Yes/no): Body Weight Reduction More Than or Equal to 5% In-trial observation period · Yes	111 Participants	44 Participants
Number of Participants Who Achieved (Yes/no): Body Weight Reduction More Than or Equal to 5% In-trial observation period · No	33 Participants	84 Participants
Number of Participants Who Achieved (Yes/no): Body Weight Reduction More Than or Equal to 5% On-treatment observation period · Yes	110 Participants	38 Participants
Number of Participants Who Achieved (Yes/no): Body Weight Reduction More Than or Equal to 5% On-treatment observation period · No	22 Participants	71 Participants

SECONDARY outcome

Timeframe: At Week 104

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

Number of participants who achieved >=10% weight loss at 104 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved >=10% weight loss, whereas 'No' infers the number of participants who have not achieved >=10% weight loss. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.

Outcome measures

Measure	Semaglutide 2.4 mg n=144 Participants Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Placebo n=128 Participants Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Number of Participants Who Achieved (Yes/no): Body Weight Reduction More Than or Equal to 10% Yes	89 Participants	17 Participants
Number of Participants Who Achieved (Yes/no): Body Weight Reduction More Than or Equal to 10% No	55 Participants	111 Participants

SECONDARY outcome

Timeframe: At Week 104

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

Number of participants who achieved >=15% weight loss at 104 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved >=15% weight loss, whereas 'No' infers the number of participants who have not achieved >=15% weight loss. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.

Outcome measures

Measure	Semaglutide 2.4 mg n=144 Participants Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Placebo n=128 Participants Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Number of Participants Who Achieved (Yes/no): Body Weight Reduction More Than or Equal to 15% Yes	75 Participants	9 Participants
Number of Participants Who Achieved (Yes/no): Body Weight Reduction More Than or Equal to 15% No	69 Participants	119 Participants

SECONDARY outcome

Timeframe: At Week 104

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

Number of participants who achieved >=20% weight loss at 104 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved >=20% weight loss, whereas 'No' infers the number of participants who have not achieved >=20% weight loss. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.

Outcome measures

Measure	Semaglutide 2.4 mg n=144 Participants Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Placebo n=128 Participants Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Number of Participants Who Achieved (Yes/no): Body Weight Reduction More Than or Equal to 20% Yes	52 Participants	3 Participants
Number of Participants Who Achieved (Yes/no): Body Weight Reduction More Than or Equal to 20% No	92 Participants	125 Participants

SECONDARY outcome

Timeframe: From Baseline (Week 0) to Week 104

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

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

Outcome measures

Measure	Semaglutide 2.4 mg n=143 Participants Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Placebo n=126 Participants Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Change From Baseline (Week 0) to Week 104 in Waist Circumference	-15.2 centimeter (cm) Standard Deviation 12.4	-4.3 centimeter (cm) Standard Deviation 9.1

SECONDARY outcome

Timeframe: From Baseline (Week 0) to Week 104

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

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

Outcome measures

Measure	Semaglutide 2.4 mg n=144 Participants Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Placebo n=128 Participants Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Change From Baseline (Week 0) to Week 104 in Body Weight (kg)	-16.9 kilogram Standard Deviation 14.0	-2.1 kilogram Standard Deviation 9.5

SECONDARY outcome

Timeframe: From Baseline (Week 0) to Week 104

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

Change in BMI from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.

Outcome measures

Measure	Semaglutide 2.4 mg n=144 Participants Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Placebo n=128 Participants Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Change From Baseline (Week 0) to Week 104 in Body Mass Index (BMI)	-6.2 kilogram per square meter (kg/m^2) Standard Deviation 5.3	-0.7 kilogram per square meter (kg/m^2) Standard Deviation 3.5

SECONDARY outcome

Timeframe: From Baseline (Week 0) to Week 104

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

Change in systolic blood pressure from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.

Outcome measures

Measure	Semaglutide 2.4 mg n=142 Participants Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Placebo n=125 Participants Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Change From Baseline (Week 0) to Week 104 in Systolic Blood Pressure	-6 millimeter of mercury (mmHg) Standard Deviation 13	-1 millimeter of mercury (mmHg) Standard Deviation 15

SECONDARY outcome

Timeframe: From Baseline (Week 0) to Week 104

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

Change in diastolic blood pressure from baseline (week 0) to week 104 is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.

Outcome measures

Measure	Semaglutide 2.4 mg n=142 Participants Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Placebo n=125 Participants Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Change From Baseline (Week 0) to Week 104 in Diastolic Blood Pressure	-4 mmHg Standard Deviation 10	-1 mmHg Standard Deviation 9

SECONDARY outcome

Timeframe: From Baseline (Week 0) to Week 104

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

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

Outcome measures

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

SECONDARY outcome

Timeframe: From Baseline (Week 0) to Week 104

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

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

Outcome measures

Measure	Semaglutide 2.4 mg n=141 Participants Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Placebo n=120 Participants Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Change in High Density Lipoprotein (HDL) Cholesterol-ratio to Baseline	1.09 Ratio of HDL cholesterol Geometric Coefficient of Variation 19.1	1.08 Ratio of HDL cholesterol Geometric Coefficient of Variation 15.4

SECONDARY outcome

Timeframe: From Baseline (Week 0) to Week 104

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

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

Outcome measures

Measure	Semaglutide 2.4 mg n=141 Participants Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Placebo n=121 Participants Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Change in Low Density Lipoprotein (LDL) Cholesterol-ratio to Baseline	0.93 Ratio of LDL cholesterol Geometric Coefficient of Variation 23.8	0.99 Ratio of LDL cholesterol Geometric Coefficient of Variation 19.1

SECONDARY outcome

Timeframe: From Baseline (Week 0) to Week 104

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

Change in VLDL cholesterol from baseline (week 0) to week 104 measured in mg/dL is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.

Outcome measures

Measure	Semaglutide 2.4 mg n=141 Participants Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Placebo n=121 Participants Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Change in Very Low Density Lipoprotein (VLDL) Cholesterol-ratio to Baseline	0.79 Ratio of VLDL cholesterol Geometric Coefficient of Variation 42.3	1.03 Ratio of VLDL cholesterol Geometric Coefficient of Variation 35.1

SECONDARY outcome

Timeframe: From Baseline (Week 0) to Week 104

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

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

Outcome measures

Measure	Semaglutide 2.4 mg n=133 Participants Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Placebo n=111 Participants Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Change in Free Fatty Acids-ratio to Baseline	0.99 Ratio of free fatty acids Geometric Coefficient of Variation 71.2	1.07 Ratio of free fatty acids Geometric Coefficient of Variation 69.1

SECONDARY outcome

Timeframe: From Baseline (Week 0) to Week 104

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

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

Outcome measures

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

SECONDARY outcome

Timeframe: From Baseline (Week 0) to Week 104

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

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

Outcome measures

Measure	Semaglutide 2.4 mg n=141 Participants Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Placebo n=121 Participants Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Change in High Sensitivity C-reactive Protein (hsCRP)-Ratio to Baseline	0.41 Ratio of hsCRP Geometric Coefficient of Variation 149.1	0.99 Ratio of hsCRP Geometric Coefficient of Variation 105.5

SECONDARY outcome

Timeframe: From Baseline (Week 0) to Week 104

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

Change in HbA1c from baseline (week 0) to week 104 in % is presented. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.

Outcome measures

Measure	Semaglutide 2.4 mg n=141 Participants Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Placebo n=122 Participants Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Change in Glycated Haemoglobin (HbA1c) (Percent [%])	-0.5 Percent of glycated haemoglobin Standard Deviation 0.3	-0.1 Percent of glycated haemoglobin Standard Deviation 0.3

SECONDARY outcome

Timeframe: From Baseline (Week 0) to Week 104

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

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

Outcome measures

Measure	Semaglutide 2.4 mg n=141 Participants Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Placebo n=122 Participants Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Change From Baseline (Week 0) to Week 104 in HbA1c (mmol/Mol)	-5.1 mmol/mol Standard Deviation 3.2	-1.0 mmol/mol Standard Deviation 3.0

SECONDARY outcome

Timeframe: From Baseline (Week 0) to Week 104

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

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

Outcome measures

Measure	Semaglutide 2.4 mg n=137 Participants Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Placebo n=117 Participants Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Change From Baseline (Week 0) to Week 104 in Fasting Plasma Glucose (FPG) (mmol/L)	-0.5 mmol/L Standard Deviation 0.5	0.1 mmol/L Standard Deviation 0.6

SECONDARY outcome

Timeframe: From Baseline (Week 0) to Week 104

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

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

Outcome measures

Measure	Semaglutide 2.4 mg n=137 Participants Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Placebo n=117 Participants Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Change From Baseline (Week 0) to Week 104 in FPG (mg/dL)	-8.3 mg/dL Standard Deviation 9.6	1.8 mg/dL Standard Deviation 10.8

SECONDARY outcome

Timeframe: From Baseline (Week 0) to Week 104

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

Change in fasting serum insulin from baseline (week 0) to week 104 measured in picomole per liter (pmol) is presented as ratio to baseline. The outcome measure was evaluated based on the data from in-trial observation period. In-trial observation period: the uninterrupted time interval from randomisation to last contact with trial site.

Outcome measures

Measure	Semaglutide 2.4 mg n=131 Participants Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Placebo n=110 Participants Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Change in Fasting Serum Insulin-ratio to Baseline (Pmol/L)	0.68 Ratio of fasting serum insulin Geometric Coefficient of Variation 54.1	0.96 Ratio of fasting serum insulin Geometric Coefficient of Variation 62.9

SECONDARY outcome

Timeframe: From Baseline (Week 0) to Week 104

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

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

Outcome measures

Measure	Semaglutide 2.4 mg n=131 Participants Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Placebo n=110 Participants Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Change in Fasting Serum Insulin-ratio to Baseline (mIU/mL)	0.68 Ratio of fasting serum insulin Geometric Coefficient of Variation 54.1	0.96 Ratio of fasting serum insulin Geometric Coefficient of Variation 62.9

SECONDARY outcome

Timeframe: From Baseline (Week 0) to Week 52

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

Percentage change in body weight from baseline (week 0) to week 52 is presented.

Outcome measures

Measure	Semaglutide 2.4 mg n=149 Participants Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Placebo n=129 Participants Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Percentage Change From Baseline (Week 0) to Week 52 in Body Weight	-15.8 percentage change Standard Deviation 9.3	-3.3 percentage change Standard Deviation 6.4

SECONDARY outcome

Timeframe: From Baseline (Week 0) to Week 52

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

Change in body weight from baseline (week 0) to week 52 in kg is presented.

Outcome measures

Measure	Semaglutide 2.4 mg n=149 Participants Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Placebo n=129 Participants Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Change From Baseline (Week 0) to Week 52 in Body Weight (kg)	-16.7 kilogram (kg) Standard Deviation 10.3	-3.5 kilogram (kg) Standard Deviation 7.4

SECONDARY outcome

Timeframe: From Baseline (Week 0) to Week 52

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

Change in BMI from baseline (week 0) to week 52 is presented.

Outcome measures

Measure	Semaglutide 2.4 mg n=149 Participants Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Placebo n=129 Participants Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Change From Baseline (Week 0) to Week 52 in Body Mass Index (BMI)	-6.1 kilogram per square meter (kg/m^2) Standard Deviation 3.8	-1.3 kilogram per square meter (kg/m^2) Standard Deviation 2.6

SECONDARY outcome

Timeframe: From Baseline (Week 0) to Week 52

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

Change in waist circumference from baseline (week 0) to week 52 is presented.

Outcome measures

Measure	Semaglutide 2.4 mg n=149 Participants Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Placebo n=129 Participants Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Change From Baseline (Week 0) to Week 52 in Waist Circumference	-14.3 centimeter (cm) Standard Deviation 9.4	-4.5 centimeter (cm) Standard Deviation 6.8

SECONDARY outcome

Timeframe: At Week 52

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

Number of participants who achieved >=5% weight loss at 52 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved >=5% weight loss, whereas 'No' infers the number of participants who have not achieved >=5% weight loss.

Outcome measures

Measure	Semaglutide 2.4 mg n=149 Participants Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Placebo n=129 Participants Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Number of Participants Who at 52 Weeks Achieved (Yes/no): Body Weight Reduction More Than or Equal to 5% Yes	132 Participants	38 Participants
Number of Participants Who at 52 Weeks Achieved (Yes/no): Body Weight Reduction More Than or Equal to 5% No	17 Participants	91 Participants

SECONDARY outcome

Timeframe: At Week 52

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

Number of participants who achieved >=10% weight loss at 52 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved >=10% weight loss, whereas 'No' infers the number of participants who have not achieved >=10% weight loss.

Outcome measures

Measure	Semaglutide 2.4 mg n=149 Participants Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Placebo n=129 Participants Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Number of Participants Who at 52 Weeks Achieved (Yes/no): Body Weight Reduction More Than or Equal to 10% Yes	102 Participants	17 Participants
Number of Participants Who at 52 Weeks Achieved (Yes/no): Body Weight Reduction More Than or Equal to 10% No	47 Participants	112 Participants

SECONDARY outcome

Timeframe: At Week 52

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

Number of participants who achieved >=15% weight loss at 52 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved >=15% weight loss, whereas 'No' infers the number of participants who have not achieved >=15% weight loss.

Outcome measures

Measure	Semaglutide 2.4 mg n=149 Participants Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Placebo n=129 Participants Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Number of Participants Who at 52 Weeks Achieved (Yes/no): Body Weight Reduction More Than or Equal to 15% Yes	78 Participants	7 Participants
Number of Participants Who at 52 Weeks Achieved (Yes/no): Body Weight Reduction More Than or Equal to 15% No	71 Participants	122 Participants

SECONDARY outcome

Timeframe: At Week 52

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

Number of participants who achieved >=20% weight loss at 52 weeks is presented. In the reported data, 'Yes' infers the number of participants who have achieved >=20% weight loss, whereas 'No' infers the number of participants who have not achieved >=20% weight loss.

Outcome measures

Measure	Semaglutide 2.4 mg n=149 Participants Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Placebo n=129 Participants Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Number of Participants Who at 52 Weeks Achieved (Yes/no): Body Weight Reduction More Than or Equal to 20% Yes	52 Participants	3 Participants
Number of Participants Who at 52 Weeks Achieved (Yes/no): Body Weight Reduction More Than or Equal to 20% No	97 Participants	126 Participants

SECONDARY outcome

Timeframe: From Baseline (Week 0) to Week 111

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

Outcome measures

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

SECONDARY outcome

Timeframe: From Baseline (Week 0) to Week 111

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

A SAE was defined as any untoward medical occurrence that at any dose results in death, or is life-threatening, or requires inpatient hospitalization or causes prolongation of existing hospitalization results in persistent or significant disability/incapacity, or may have caused a congenital anomaly/birth defect, or requires intervention to prevent permanent impairment or damage. The SAEs occurred from week 0 to week 111 is presented. The outcome measure was evaluated based on the data from on-treatment observation period, which was defined as the interval from first to last trial product administration plus 7 weeks of follow-up and excluding any period of temporary treatment interruption defined as >7 consecutive missed doses (corresponding to >7 weeks off-treatment).

Outcome measures

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

SECONDARY outcome

Timeframe: From Baseline (Week 0) to Week 104

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

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

Outcome measures

Measure	Semaglutide 2.4 mg n=130 Participants Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Placebo n=106 Participants Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Change From Baseline (Week 0) to Week 104 in Pulse	3 beats per minute (beats/min) Standard Deviation 10	-1 beats per minute (beats/min) Standard Deviation 9

SECONDARY outcome

Timeframe: From Baseline (Week 0) to Week 104

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

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

Outcome measures

Measure	Semaglutide 2.4 mg n=130 Participants Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Placebo n=106 Participants Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Change From Baseline (Week 0) to Week 104 in Amylase	1.13 Units/liter (U/L) Geometric Coefficient of Variation 20.7	1.02 Units/liter (U/L) Geometric Coefficient of Variation 15.1

SECONDARY outcome

Timeframe: From Baseline (Week 0) to Week 104

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

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

Outcome measures

Measure	Semaglutide 2.4 mg n=130 Participants Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Placebo n=106 Participants Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Change From Baseline (Week 0) to Week 104 in Lipase	1.47 U/L Geometric Coefficient of Variation 52.3	1.00 U/L Geometric Coefficient of Variation 34.4

SECONDARY outcome

Timeframe: From Baseline (Week 0) to Week 104

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

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

Outcome measures

Measure	Semaglutide 2.4 mg n=124 Participants Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Placebo n=102 Participants Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Change From Baseline (Week 0) to Week 104 in Calcitonin	0.99 nanogram per liter (ng/L) Geometric Coefficient of Variation 21.5	0.97 nanogram per liter (ng/L) Geometric Coefficient of Variation 41.0

Adverse Events

Semaglutide 2.4 mg

Serious events: 12 serious events

Other events: 141 other events

Deaths: 1 deaths

Placebo

Serious events: 18 serious events

Other events: 117 other events

Deaths: 0 deaths

Serious adverse events

Measure	Semaglutide 2.4 mg n=152 participants at risk Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Placebo n=152 participants at risk Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Congenital, familial and genetic disorders Arnold-Chiari malformation	0.00% 0/152 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	0.66% 1/152 • Number of events 1 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign uterine neoplasm	0.66% 1/152 • Number of events 1 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	0.00% 0/152 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Gastrointestinal disorders Abdominal adhesions	0.66% 1/152 • Number of events 1 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	0.00% 0/152 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Cardiac disorders Acute myocardial infarction	0.66% 1/152 • Number of events 1 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	0.00% 0/152 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Infections and infestations Anal abscess	0.00% 0/152 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	0.66% 1/152 • Number of events 1 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Infections and infestations Appendicitis	0.00% 0/152 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	0.66% 1/152 • Number of events 1 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Infections and infestations Appendicitis perforated	0.66% 1/152 • Number of events 1 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	0.00% 0/152 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Infections and infestations COVID-19	0.66% 1/152 • Number of events 1 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	1.3% 2/152 • Number of events 2 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Infections and infestations COVID-19 pneumonia	0.00% 0/152 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	0.66% 1/152 • Number of events 1 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Nervous system disorders Cervical cord compression	0.00% 0/152 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	0.66% 1/152 • Number of events 1 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Hepatobiliary disorders Cholecystitis	0.66% 1/152 • Number of events 1 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	0.00% 0/152 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Hepatobiliary disorders Cholecystitis acute	0.66% 1/152 • Number of events 1 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	0.00% 0/152 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Hepatobiliary disorders Cholelithiasis	1.3% 2/152 • Number of events 2 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	0.00% 0/152 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Infections and infestations Colonic abscess	0.66% 1/152 • Number of events 1 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	0.00% 0/152 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Vascular disorders Deep vein thrombosis	0.66% 1/152 • Number of events 1 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	0.00% 0/152 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Infections and infestations Diverticulitis	0.66% 1/152 • Number of events 1 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	0.00% 0/152 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Musculoskeletal and connective tissue disorders Foot deformity	0.66% 1/152 • Number of events 1 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	0.66% 1/152 • Number of events 1 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Gastrointestinal disorders Gastritis	0.00% 0/152 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	0.66% 1/152 • Number of events 1 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.66% 1/152 • Number of events 1 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	0.00% 0/152 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Infections and infestations Herpes zoster	0.00% 0/152 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	0.66% 1/152 • Number of events 1 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Invasive ductal breast carcinoma	0.00% 0/152 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	1.3% 2/152 • Number of events 2 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Injury, poisoning and procedural complications Jaw fracture	0.00% 0/152 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	0.66% 1/152 • Number of events 1 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	0.00% 0/152 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	0.66% 1/152 • Number of events 1 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Renal and urinary disorders Nephrolithiasis	0.66% 1/152 • Number of events 1 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	0.00% 0/152 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Psychiatric disorders Panic disorder	0.66% 1/152 • Number of events 1 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	0.00% 0/152 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Infections and infestations Perineal abscess	0.66% 1/152 • Number of events 1 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	0.00% 0/152 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Infections and infestations Pneumonia	0.00% 0/152 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	0.66% 1/152 • Number of events 1 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.66% 1/152 • Number of events 1 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	0.00% 0/152 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Injury, poisoning and procedural complications Rib fracture	0.00% 0/152 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	0.66% 1/152 • Number of events 1 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	0.00% 0/152 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	0.66% 1/152 • Number of events 1 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Small cell lung cancer metastatic	0.00% 0/152 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	0.66% 1/152 • Number of events 1 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Nervous system disorders Tension headache	0.00% 0/152 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	0.66% 1/152 • Number of events 1 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Surgical and medical procedures Thyroidectomy	0.00% 0/152 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	0.66% 1/152 • Number of events 1 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.

Other adverse events

Measure	Semaglutide 2.4 mg n=152 participants at risk Participants received once-weekly s.c injection of semaglutide in 16 week dose escalation period with dose escalation (0.25 mg, 0.5 mg, 1.0 mg and 1.7 mg) every fourth week until maintenance dose of 2.4 mg of semaglutide was reached. Treatment was continued on the maintenance dose of 2.4 mg once weekly for an additional 88 weeks until week 104.	Placebo n=152 participants at risk Participants received once-weekly s.c. injection of placebo matched to semaglutide for 104 weeks.
Gastrointestinal disorders Eructation	11.2% 17/152 • Number of events 21 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	0.66% 1/152 • Number of events 2 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
General disorders Fatigue	7.2% 11/152 • Number of events 12 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	5.3% 8/152 • Number of events 8 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Gastrointestinal disorders Abdominal distension	9.9% 15/152 • Number of events 22 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	5.9% 9/152 • Number of events 13 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Gastrointestinal disorders Abdominal pain	13.2% 20/152 • Number of events 32 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	2.6% 4/152 • Number of events 14 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Gastrointestinal disorders Abdominal pain upper	14.5% 22/152 • Number of events 23 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	6.6% 10/152 • Number of events 13 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Psychiatric disorders Anxiety	5.3% 8/152 • Number of events 8 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	7.2% 11/152 • Number of events 12 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Musculoskeletal and connective tissue disorders Arthralgia	9.2% 14/152 • Number of events 20 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	7.2% 11/152 • Number of events 20 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
General disorders Asthenia	5.3% 8/152 • Number of events 10 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	1.3% 2/152 • Number of events 3 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Musculoskeletal and connective tissue disorders Back pain	9.9% 15/152 • Number of events 17 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	12.5% 19/152 • Number of events 20 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Infections and infestations Bronchitis	5.3% 8/152 • Number of events 9 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	5.3% 8/152 • Number of events 9 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Infections and infestations COVID-19	9.9% 15/152 • Number of events 16 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	3.9% 6/152 • Number of events 6 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Gastrointestinal disorders Constipation	30.9% 47/152 • Number of events 62 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	11.2% 17/152 • Number of events 26 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Respiratory, thoracic and mediastinal disorders Cough	5.3% 8/152 • Number of events 8 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	5.3% 8/152 • Number of events 10 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Metabolism and nutrition disorders Decreased appetite	11.2% 17/152 • Number of events 18 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	3.9% 6/152 • Number of events 6 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Gastrointestinal disorders Diarrhoea	34.9% 53/152 • Number of events 108 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	23.7% 36/152 • Number of events 51 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Nervous system disorders Dizziness	8.6% 13/152 • Number of events 16 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	5.3% 8/152 • Number of events 12 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Gastrointestinal disorders Dyspepsia	13.2% 20/152 • Number of events 24 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	4.6% 7/152 • Number of events 12 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Gastrointestinal disorders Flatulence	13.2% 20/152 • Number of events 25 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	6.6% 10/152 • Number of events 11 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Infections and infestations Gastroenteritis	13.2% 20/152 • Number of events 28 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	2.6% 4/152 • Number of events 4 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Gastrointestinal disorders Gastrooesophageal reflux disease	9.9% 15/152 • Number of events 19 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	3.9% 6/152 • Number of events 6 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Nervous system disorders Headache	10.5% 16/152 • Number of events 36 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	10.5% 16/152 • Number of events 31 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Vascular disorders Hypertension	3.9% 6/152 • Number of events 6 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	9.2% 14/152 • Number of events 14 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Infections and infestations Influenza	13.2% 20/152 • Number of events 23 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	10.5% 16/152 • Number of events 19 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
General disorders Injection site bruising	3.3% 5/152 • Number of events 8 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	5.3% 8/152 • Number of events 11 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Injury, poisoning and procedural complications Ligament sprain	6.6% 10/152 • Number of events 10 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	0.66% 1/152 • Number of events 1 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Infections and infestations Nasopharyngitis	15.8% 24/152 • Number of events 33 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	15.1% 23/152 • Number of events 31 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Gastrointestinal disorders Nausea	53.3% 81/152 • Number of events 213 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	21.7% 33/152 • Number of events 53 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Musculoskeletal and connective tissue disorders Osteoarthritis	5.9% 9/152 • Number of events 10 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	5.3% 8/152 • Number of events 9 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Infections and infestations Sinusitis	5.3% 8/152 • Number of events 8 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	5.9% 9/152 • Number of events 9 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Infections and infestations Upper respiratory tract infection	13.2% 20/152 • Number of events 31 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	15.1% 23/152 • Number of events 30 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Infections and infestations Urinary tract infection	7.9% 12/152 • Number of events 19 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	3.9% 6/152 • Number of events 7 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.
Gastrointestinal disorders Vomiting	30.3% 46/152 • Number of events 78 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.	4.6% 7/152 • Number of events 8 • From Baseline (Week 0) to Week 111 All AEs mentioned here are TEAE defined as an event that had onset date (or increase in severity) on or after the first day of exposure to randomized treatment and no later than the date of last dose + 7 weeks. Results are based on the SAS which included all randomized participants exposed to at least one dose of randomized treatment.

Additional Information

Clinical Reporting Office (1452)

Novo Nordisk A/S

Phone: (+1) 866-867-7178

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
• Publication restrictions are in place

Restriction type: OTHER