Trial Outcomes & Findings for Investigation of Efficacy and Safety of Three Dose Levels of Subcutaneous Semaglutide Once Daily Versus Placebo in Subjects With Non-alcoholic Steatohepatitis. (NCT NCT02970942)

Results Overview

NASH resolution defined by NASH clinical research network as lobular inflammation of 0 or 1 and hepatocellular ballooning reduced to 0; both criteria were necessary conditions. Hepatocellular ballooning ranges from 0-2; lobular inflammation ranges from 0-3, with higher scores indicating more severe hepatocellular ballooning or lobular inflammation. Worsening of fibrosis defined by an increase in fibrosis at least one stage of Kleiner fibrosis classification: fibrosis stages range from 0-4, with higher scores indicating greater fibrosis (0=None, 4=Cirrhosis). Endpoint was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

320 participants

Primary outcome timeframe

After 72 weeks

Results posted on

2021-11-16

Participant Flow

The trial was conducted at 114 sites in 16 countries as follows (number of sites that screened participants/ number of sites that randomised participants): Australia (4/ 3); Austria (3/ 3); Belgium (4/ 4); Bulgaria (2/ 2); Canada (9/ 7); Denmark (2/ 2); Finland (1/ 1); France (8/ 6); Greece (5/ 5); Japan (13/ 12); Netherlands (7/ 5); Russian Federation (25/ 17); Spain (6/ 5); Sweden (3/ 2); United Kingdom (15/ 11); United States (36/ 29).

Participants were randomised in a 3:3:3:1:1:1 ratio to receive once-daily semaglutide or placebo subcutaneously. After randomisation, the participants entered a dose-escalation period, with increase in dose every 4 weeks until the target dose was reached.

Participant milestones

Participant milestones
Measure	Semaglutide 0.1 mg Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Overall Study STARTED	80	78	82	80
Overall Study Full Analysis Set	80	78	82	80
Overall Study Safety Analysis Set	80	78	81	80
Overall Study Exposed	80	78	81	80
Overall Study COMPLETED	76	72	77	77
Overall Study NOT COMPLETED	4	6	5	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Semaglutide 0.1 mg Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Overall Study Death	0	1	0	0
Overall Study Lost to Follow-up	1	0	2	1
Overall Study Withdrawal by Subject	3	5	3	2

Baseline Characteristics

Investigation of Efficacy and Safety of Three Dose Levels of Subcutaneous Semaglutide Once Daily Versus Placebo in Subjects With Non-alcoholic Steatohepatitis.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Semaglutide 0.1 mg n=80 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=78 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=82 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=80 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.	Total n=320 Participants Total of all reporting groups
Age, Continuous	55.2 years STANDARD_DEVIATION 10.9 • n=5 Participants	58.1 years STANDARD_DEVIATION 9.9 • n=7 Participants	54.3 years STANDARD_DEVIATION 10.2 • n=5 Participants	52.4 years STANDARD_DEVIATION 10.8 • n=4 Participants	55.0 years STANDARD_DEVIATION 10.6 • n=21 Participants
Sex: Female, Male Female	51 Participants n=5 Participants	52 Participants n=7 Participants	47 Participants n=5 Participants	44 Participants n=4 Participants	194 Participants n=21 Participants
Sex: Female, Male Male	29 Participants n=5 Participants	26 Participants n=7 Participants	35 Participants n=5 Participants	36 Participants n=4 Participants	126 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	7 Participants n=5 Participants	10 Participants n=7 Participants	14 Participants n=5 Participants	9 Participants n=4 Participants	40 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	69 Participants n=5 Participants	63 Participants n=7 Participants	65 Participants n=5 Participants	66 Participants n=4 Participants	263 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	5 Participants n=7 Participants	3 Participants n=5 Participants	5 Participants n=4 Participants	17 Participants n=21 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	3 Participants n=21 Participants
Race/Ethnicity, Customized Asian	10 Participants n=5 Participants	12 Participants n=7 Participants	14 Participants n=5 Participants	12 Participants n=4 Participants	48 Participants n=21 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race/Ethnicity, Customized White	65 Participants n=5 Participants	59 Participants n=7 Participants	62 Participants n=5 Participants	62 Participants n=4 Participants	248 Participants n=21 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	2 Participants n=21 Participants
Race/Ethnicity, Customized Not applicable	4 Participants n=5 Participants	5 Participants n=7 Participants	3 Participants n=5 Participants	5 Participants n=4 Participants	17 Participants n=21 Participants

PRIMARY outcome

Timeframe: After 72 weeks

Population: Full analysis set included all randomised participants. Overall number of participants analysed = Number of participants with fibrosis stage 2 or 3 at baseline who contributed to the analysis. In below table, 'Yes' infers percentage of participants who achieved NASH resolution without worsening of fibrosis and 'No' infers vice-versa; 'Missing' refers to percentage of participants with data missing due to different reasons (lost to follow-up, withdrawal).

NASH resolution defined by NASH clinical research network as lobular inflammation of 0 or 1 and hepatocellular ballooning reduced to 0; both criteria were necessary conditions. Hepatocellular ballooning ranges from 0-2; lobular inflammation ranges from 0-3, with higher scores indicating more severe hepatocellular ballooning or lobular inflammation. Worsening of fibrosis defined by an increase in fibrosis at least one stage of Kleiner fibrosis classification: fibrosis stages range from 0-4, with higher scores indicating greater fibrosis (0=None, 4=Cirrhosis). Endpoint was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=57 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=59 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=56 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=58 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Percentage of Participants With Non- Alcoholic Steatohepatitis (NASH) Resolution Without Worsening of Fibrosis After 72 Weeks (Yes/No) Yes	40.4 Percentage of participants	35.6 Percentage of participants	58.9 Percentage of participants	17.2 Percentage of participants
Percentage of Participants With Non- Alcoholic Steatohepatitis (NASH) Resolution Without Worsening of Fibrosis After 72 Weeks (Yes/No) No	54.4 Percentage of participants	47.5 Percentage of participants	30.4 Percentage of participants	74.1 Percentage of participants
Percentage of Participants With Non- Alcoholic Steatohepatitis (NASH) Resolution Without Worsening of Fibrosis After 72 Weeks (Yes/No) Missing	5.3 Percentage of participants	16.9 Percentage of participants	10.7 Percentage of participants	8.6 Percentage of participants

SECONDARY outcome

Timeframe: After 72 weeks

Population: Full analysis set included all randomised participants. Overall number of participants analysed = Number of participants with fibrosis stage 2 or 3 at baseline who contributed to the analysis. In below table, 'Yes' infers percentage of participants who achieved at least one stage of fibrosis improvement with no worsening of NASH; 'No' infers vice-versa; 'Missing' refers to percentage of participants with data missing due to different reasons (lost to follow-up, withdrawal).

NASH resolution defined by NASH clinical research network as lobular inflammation of 0 or 1; hepatocellular ballooning reduced to 0; both criteria were necessary conditions. Hepatocellular ballooning range: 0-2; lobular inflammation range: 0-3, with higher scores indicating more severe hepatocellular ballooning or lobular inflammation. Worsening of fibrosis defined by an increase in fibrosis at least one stage of Kleiner fibrosis classification: fibrosis stages range from 0-4, higher scores indicate greater fibrosis (0=None, 4=Cirrhosis). Endpoint was evaluated based on data from in-trial period which started on date of randomisation visit and ended on first of following dates (both inclusive):1) follow-up visit (Week 79); 2) withdrawal of consent; 3)last contact with participant (for participants lost to follow-up); 4)death.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=57 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=59 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=56 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=58 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Percentage of Participants With at Least One Stage of Liver Fibrosis Improvement With no Worsening of NASH After 72 Weeks (Yes/No) Yes	49.1 Percentage of participants	32.2 Percentage of participants	42.9 Percentage of participants	32.8 Percentage of participants
Percentage of Participants With at Least One Stage of Liver Fibrosis Improvement With no Worsening of NASH After 72 Weeks (Yes/No) No	45.6 Percentage of participants	50.8 Percentage of participants	46.4 Percentage of participants	58.6 Percentage of participants
Percentage of Participants With at Least One Stage of Liver Fibrosis Improvement With no Worsening of NASH After 72 Weeks (Yes/No) Missing	5.3 Percentage of participants	16.9 Percentage of participants	10.7 Percentage of participants	8.6 Percentage of participants

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Full analysis set included all randomised participants.

Percentage of participants who had worsened, improved or had no change in total NAS from baseline to week 72 is presented. Worsening is defined as an increase of at least 1 in the NAS; Improvement is defined as a decrease of at least 1 in the NAS; while no change corresponds to no change in NAS from baseline to week 72. NAS is calculated as the sum of scores for steatosis (0 to 3), lobular inflammation (0 to 3), and hepatocyte ballooning (0 to 2). Therefore, it is assessed on a scale of 0-8, with higher scores indicating more severe disease. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=80 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=78 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=82 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=80 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Percentage of Participants With Change in Total NAFLD (Non- Alcoholic Fatty Liver Disease) Activity Score (NAS) Improvement	71.3 Percentage of participants	79.5 Percentage of participants	82.9 Percentage of participants	43.8 Percentage of participants
Percentage of Participants With Change in Total NAFLD (Non- Alcoholic Fatty Liver Disease) Activity Score (NAS) Worsening	7.5 Percentage of participants	2.6 Percentage of participants	3.7 Percentage of participants	16.3 Percentage of participants
Percentage of Participants With Change in Total NAFLD (Non- Alcoholic Fatty Liver Disease) Activity Score (NAS) No change	13.8 Percentage of participants	5.1 Percentage of participants	1.2 Percentage of participants	27.5 Percentage of participants
Percentage of Participants With Change in Total NAFLD (Non- Alcoholic Fatty Liver Disease) Activity Score (NAS) Missing	7.5 Percentage of participants	12.8 Percentage of participants	12.2 Percentage of participants	12.5 Percentage of participants

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Full analysis set included all randomised participants.

Percentage of participants who had improved, worsened, or had no change in steatosis from baseline to week 72 is presented. Steatosis was assessed on a scale of 0-3, with higher scores indicating more severe steatosis. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=80 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=78 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=82 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=80 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Percentage of Participants With Change in Steatosis Improvement	52.5 Percentage of participants	60.3 Percentage of participants	63.4 Percentage of participants	26.3 Percentage of participants
Percentage of Participants With Change in Steatosis Worsening	6.3 Percentage of participants	2.6 Percentage of participants	3.7 Percentage of participants	15.0 Percentage of participants
Percentage of Participants With Change in Steatosis No change	33.8 Percentage of participants	24.4 Percentage of participants	20.7 Percentage of participants	46.3 Percentage of participants
Percentage of Participants With Change in Steatosis Missing	7.5 Percentage of participants	12.8 Percentage of participants	12.2 Percentage of participants	12.5 Percentage of participants

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Full analysis set included all randomised participants.

Percentage of participants who had improved, worsened, or had no change in lobular inflammation from baseline to week 72 is presented. Lobular inflammation was assessed on a scale of 0-3, with higher scores indicating more severe lobular inflammation. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=80 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=78 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=82 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=80 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Percentage of Participants With Change in Lobular Inflammation Improvement	41.3 Percentage of participants	47.4 Percentage of participants	37.8 Percentage of participants	26.3 Percentage of participants
Percentage of Participants With Change in Lobular Inflammation Worsening	7.5 Percentage of participants	7.7 Percentage of participants	6.1 Percentage of participants	17.5 Percentage of participants
Percentage of Participants With Change in Lobular Inflammation No change	43.8 Percentage of participants	32.1 Percentage of participants	43.9 Percentage of participants	45.0 Percentage of participants
Percentage of Participants With Change in Lobular Inflammation Missing	7.5 Percentage of participants	12.8 Percentage of participants	12.2 Percentage of participants	11.3 Percentage of participants

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Full analysis set included all randomised participants.

Percentage of participants who had improved, worsened, or had no change in hepatocyte ballooning from baseline to week 72 is presented. Hepatocyte ballooning was assessed on a scale of 0-2, with higher scores indicating more severe disease. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=80 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=78 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=82 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=80 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Percentage of Participants With Change in Hepatocyte Ballooning Improvement	61.3 Percentage of participants	70.5 Percentage of participants	74.4 Percentage of participants	38.8 Percentage of participants
Percentage of Participants With Change in Hepatocyte Ballooning Worsening	2.5 Percentage of participants	2.6 Percentage of participants	1.2 Percentage of participants	2.5 Percentage of participants
Percentage of Participants With Change in Hepatocyte Ballooning No change	28.8 Percentage of participants	14.1 Percentage of participants	12.2 Percentage of participants	46.3 Percentage of participants
Percentage of Participants With Change in Hepatocyte Ballooning Missing	7.5 Percentage of participants	12.8 Percentage of participants	12.2 Percentage of participants	12.5 Percentage of participants

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Full analysis set included all randomised participants.

Percentage of participants who had improved, worsened, or had no change in fibrosis stage from baseline to week 72 is presented. The degree of fibrosis is described by the Kleiner fibrosis staging system, ranging from F0 (absence of fibrosis), F1 (portal/perisinusoidal fibrosis), F2 (perisinusoidal and portal/periportal fibrosis), F3 (septal or bridging fibrosis) through F4 (cirrhosis). The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=80 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=78 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=82 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=80 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Percentage of Participants With Change in Fibrosis Stage According to the Kleiner Fibrosis Classification Improvement	46.3 Percentage of participants	32.1 Percentage of participants	42.7 Percentage of participants	31.3 Percentage of participants
Percentage of Participants With Change in Fibrosis Stage According to the Kleiner Fibrosis Classification Worsening	10.0 Percentage of participants	7.7 Percentage of participants	4.9 Percentage of participants	18.8 Percentage of participants
Percentage of Participants With Change in Fibrosis Stage According to the Kleiner Fibrosis Classification No change	36.3 Percentage of participants	42.3 Percentage of participants	36.6 Percentage of participants	37.5 Percentage of participants
Percentage of Participants With Change in Fibrosis Stage According to the Kleiner Fibrosis Classification Missing	7.5 Percentage of participants	17.9 Percentage of participants	15.9 Percentage of participants	12.5 Percentage of participants

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Full analysis set included all randomised participants.

Percentage of participants who had improved, worsened, or had no change in the activity component of the SAF score from baseline to week 72 is presented. SAF score was assessed on a scale of 0-4, with higher scores indicating more severe disease. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=80 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=78 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=82 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=80 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Percentage of Participants With Change in Activity Component of Steatosis-activity-fibrosis (SAF) Score Improvement	62.5 Percentage of participants	71.8 Percentage of participants	72.0 Percentage of participants	42.5 Percentage of participants
Percentage of Participants With Change in Activity Component of Steatosis-activity-fibrosis (SAF) Score Worsening	7.5 Percentage of participants	3.8 Percentage of participants	1.2 Percentage of participants	11.3 Percentage of participants
Percentage of Participants With Change in Activity Component of Steatosis-activity-fibrosis (SAF) Score No change	22.5 Percentage of participants	11.5 Percentage of participants	14.6 Percentage of participants	33.8 Percentage of participants
Percentage of Participants With Change in Activity Component of Steatosis-activity-fibrosis (SAF) Score Missing	7.5 Percentage of participants	12.8 Percentage of participants	12.2 Percentage of participants	12.5 Percentage of participants

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Full analysis set included all randomised participants. Overall number of participants analysed = Number of participants who contributed to the analysis

Change in fibrosis-4 score is presented as ratio to baseline. Fibrosis-4 is the ratio of age in years and aminotransferase to platelet count. It is a non-invasive hepatic fibrosis index score combining standard biochemical values, platelets, alanine aminotransferase (ALT), AST and age that is calculated using formula: Fibrosis-4 = (Age \[years\] x AST \[U/L\]) / (platelets \[10\^9/L\] x (square root of ALT \[U/L\])). A Fibrosis-4 index of \< 1.45 indicated no or moderate fibrosis and an index of \> 3.25 indicated extensive fibrosis/cirrhosis. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=71 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=63 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=72 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=67 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Fibrosis-4 Score	0.81 Ratio of fibrosis-4 score Geometric Coefficient of Variation 36.8	0.77 Ratio of fibrosis-4 score Geometric Coefficient of Variation 32.4	0.77 Ratio of fibrosis-4 score Geometric Coefficient of Variation 31.3	0.95 Ratio of fibrosis-4 score Geometric Coefficient of Variation 43.1

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Full analysis set included all randomised participants. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in NFS from baseline to week 72 is presented. NFS is calculated using formula: NFS = -1.675 + 0.037 \* age (years) + 0.094 \* body mass index (BMI) (kg/m\^2) + 1.13 \* hyperglycaemia (yes/no) + 0.99 \* Aspartate aminotransferase (AST)/ Alanine aminotransferase (ALT) ratio + 0.013 × platelet count (\*10\^9/L) - 0.66 \* albumin (g/dL). The score is used to classify the probability of fibrosis. A score a) \< -1.5 indicates a low probability, b) \> -1.5 to \< 0.67 indicates intermediate probability, and a score of c) \> 0.67 indicates a high probability of liver fibrosis. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=71 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=63 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=72 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=66 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in NAFLD Fibrosis Score (NFS)	-0.322 Score on a scale Standard Deviation 0.819	-0.617 Score on a scale Standard Deviation 0.691	-0.475 Score on a scale Standard Deviation 0.770	-0.040 Score on a scale Standard Deviation 0.844

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Full analysis set included all randomised participants. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in ALT (measured as units per liter) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=76 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=71 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=77 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=75 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Alanine Aminotransferase (ALT)	0.62 Ratio of ALT Geometric Coefficient of Variation 62.7	0.57 Ratio of ALT Geometric Coefficient of Variation 62.1	0.40 Ratio of ALT Geometric Coefficient of Variation 68.2	0.80 Ratio of ALT Geometric Coefficient of Variation 60.3

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Full analysis set included all randomised participants. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in AST (measured as units per liter) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=74 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=69 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=77 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=74 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Aspartate Aminotransferase (AST)	0.66 Ratio of AST Geometric Coefficient of Variation 55.1	0.63 Ratio of AST Geometric Coefficient of Variation 46.6	0.50 Ratio of AST Geometric Coefficient of Variation 45.8	0.84 Ratio of AST Geometric Coefficient of Variation 62.3

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Full analysis set included all randomised participants. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in GGT (measured as units per liter) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=76 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=71 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=77 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=75 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Gamma Glutamyl Transferase (GGT)	0.76 Ratio of GGT Geometric Coefficient of Variation 52.0	0.64 Ratio of GGT Geometric Coefficient of Variation 51.6	0.48 Ratio of GGT Geometric Coefficient of Variation 60.2	0.92 Ratio of GGT Geometric Coefficient of Variation 46.6

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Full analysis set included all randomised participants. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in albumin (measured as grams per deciliter) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=76 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=71 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=77 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=75 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Albumin	1.02 Ratio of albumin Geometric Coefficient of Variation 5.6	1.01 Ratio of albumin Geometric Coefficient of Variation 6.0	1.01 Ratio of albumin Geometric Coefficient of Variation 5.4	1.02 Ratio of albumin Geometric Coefficient of Variation 6.0

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Full analysis set included all randomised participants. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in INR is presented as ratio to baseline. INR is the ratio of measured prothrombin time over normal prothrombin time and it evaluates the extrinsic coagulation pathway (vitamin K dependent clotting factors II; V, VII, IX and X). These clotting factors are synthesised in the liver, thus INR is used as a marker of liver synthesis function. The therapeutic INR range varies, most commonly an INR 2-3 goal, but ranging from 1.5-4.0. Bleeding complications are more likely to occur above an INR value of 4.0. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=76 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=71 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=76 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=75 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in International Normalized Ratio (INR)	0.97 Ratio of INR Geometric Coefficient of Variation 18.8	0.96 Ratio of INR Geometric Coefficient of Variation 11.8	0.93 Ratio of INR Geometric Coefficient of Variation 22.3	0.99 Ratio of INR Geometric Coefficient of Variation 19.3

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Full analysis set included all randomised participants. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in ELF from baseline to week 72 is presented. The ELF discriminant score was derived as a log-linear combination of the markers hyaluronic acid (HA), amino-terminal propeptide of type III collagen (PIIINP) and tissue inhibitor of metalloproteinase 1 (TIMP1). ELF score = -7.412 + 0.681 × ln(HA (nanograms per millilitre (ng/mL)) + 0.775 × ln(P3NP (ng/mL)) + 0.494 × ln(TIMP1 (ng/mL)). ELF score: a) \< 7.7: no to mild fibrosis; b) ≥ 7.7 - \< 9.8: Moderate fibrosis; c) ≥ 9.8 - \< 11.3: Severe fibrosis; d) ≥ 11.3: Cirrhosis. A negative change from baseline indicates decreased fibrosis. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=76 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=70 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=76 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=75 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Enhanced Liver Fibrosis (ELF)	-0.4 score on a scale Standard Deviation 0.7	-0.4 score on a scale Standard Deviation 0.8	-0.6 score on a scale Standard Deviation 0.8	0.1 score on a scale Standard Deviation 0.7

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Full analysis set included all randomised participants. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in CK-18 fragments (M30, M65) (measured as units per liter) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=76 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=71 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=76 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=74 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Cytokeratin 18 (CK-18) Fragments M30	0.52 Ratio of CK-18 fragments Geometric Coefficient of Variation 84.2	0.50 Ratio of CK-18 fragments Geometric Coefficient of Variation 76.4	0.40 Ratio of CK-18 fragments Geometric Coefficient of Variation 74.5	0.78 Ratio of CK-18 fragments Geometric Coefficient of Variation 106.9
Change in Cytokeratin 18 (CK-18) Fragments M65	0.51 Ratio of CK-18 fragments Geometric Coefficient of Variation 73.1	0.52 Ratio of CK-18 fragments Geometric Coefficient of Variation 62.5	0.38 Ratio of CK-18 fragments Geometric Coefficient of Variation 65.6	0.71 Ratio of CK-18 fragments Geometric Coefficient of Variation 83.7

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Full analysis set included all randomised participants.Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in miR-122 (measured as 1/microliter) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=73 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=71 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=76 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=74 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in microRNA 122 (miR-122)	0.86 Ratio of miR-122 Geometric Coefficient of Variation 151.8	0.74 Ratio of miR-122 Geometric Coefficient of Variation 203.1	0.58 Ratio of miR-122 Geometric Coefficient of Variation 161.3	1.28 Ratio of miR-122 Geometric Coefficient of Variation 194.3

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Full analysis set included all randomised participants. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in interleukin-1 receptor (IL-1R) antagonist (measured as picograms per milliliter) antagonist is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=69 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=65 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=74 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=69 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Interleukin-1 Receptor (IL-1R) Antagonist	0.87 Ratio of IL-1R antagonist Geometric Coefficient of Variation 49.3	0.85 Ratio of IL-1R antagonist Geometric Coefficient of Variation 37.5	0.73 Ratio of IL-1R antagonist Geometric Coefficient of Variation 47.9	0.94 Ratio of IL-1R antagonist Geometric Coefficient of Variation 41.7

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Full analysis set included all randomised participants. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in MCP-1 (measured as picograms per milliliter) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=75 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=71 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=76 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=73 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Monocyte Chemoattractant Protein 1 (MCP-1)	1.07 Ratio of MCP-1 Geometric Coefficient of Variation 23.3	1.08 Ratio of MCP-1 Geometric Coefficient of Variation 29.8	0.99 Ratio of MCP-1 Geometric Coefficient of Variation 30.7	1.04 Ratio of MCP-1 Geometric Coefficient of Variation 26.4

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Full analysis set included all randomised participants. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in FGF-21 (measured as picograms per milliliter) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=76 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=71 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=77 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=74 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Fibroblast Growth Factor 21 (FGF-21)	0.72 Ratio of FGF-21 Geometric Coefficient of Variation 86.1	0.61 Ratio of FGF-21 Geometric Coefficient of Variation 104.1	0.55 Ratio of FGF-21 Geometric Coefficient of Variation 91.3	0.76 Ratio of FGF-21 Geometric Coefficient of Variation 64.8

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Full analysis set included all randomised participants. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in liver stiffness (measured as kilopascal (kPa)) assessed by FibroScan® is presented as ratio to baseline. FibroScan® is a specialized ultrasound machine for the liver. It measures fibrosis (scarring) by measuring the stiffness of the liver. It's normally between 2 and 6 kPa. Many people with liver disease(s) have a result that's higher than the normal range. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=47 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=49 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=46 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=45 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Liver Stiffness Assessed by FibroScan®	0.72 Ratio of liver stiffness Geometric Coefficient of Variation 49.3	0.64 Ratio of liver stiffness Geometric Coefficient of Variation 52.2	0.66 Ratio of liver stiffness Geometric Coefficient of Variation 58.4	1.18 Ratio of liver stiffness Geometric Coefficient of Variation 71.2

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Full analysis set included all randomised participants. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in liver steatosis assessed by FibroScan® from baseline to week 72 is presented. FibroScan® is a specialized ultrasound machine for the liver. It measures fibrosis (scarring) and steatosis (fatty change) in the liver. Fatty change is fat building up in the liver cells. To assess liver steatosis, the controlled attenuation parameter (CAP; giving an estimate of ultrasound attenuation ∼3.5 MegaHertz (MHz)) is available with the M probe of the FibroScan. The CAP score is measured in decibels per meter (dB/m). It ranges from 100 to 400 dB/m, with higher scores indicating higher amount of liver with fatty change. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=34 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=37 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=33 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=35 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Liver Steatosis Assessed by FibroScan®	-5.8 Decibels per meter Standard Deviation 41.1	-50.9 Decibels per meter Standard Deviation 64.3	-42.1 Decibels per meter Standard Deviation 73.3	-18.7 Decibels per meter Standard Deviation 43.3

SECONDARY outcome

Timeframe: Week 72

Population: Full analysis set included all randomised participants.

Percentage of participants with weight loss of greater than or equal to (≥) 5% of baseline body weight at 72 weeks is presented. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death. In the below table, 'Yes' infers percentage of participants who have achieved ≥ 5% weight loss; 'No' infers percentage of participants who have not achieved ≥ 5% weight loss at 72 weeks and 'Missing' refers to percentage of participants with data missing due to different reasons (lost to follow-up, withdrawal).

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=80 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=78 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=82 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=80 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Percentage of Participants With Weight Loss of ≥ 5% of Baseline Body Weight at 72 Weeks (Yes/No) Yes	43.8 Percentage of participants	62.8 Percentage of participants	76.8 Percentage of participants	16.3 Percentage of participants
Percentage of Participants With Weight Loss of ≥ 5% of Baseline Body Weight at 72 Weeks (Yes/No) No	51.3 Percentage of participants	28.2 Percentage of participants	17.1 Percentage of participants	78.8 Percentage of participants
Percentage of Participants With Weight Loss of ≥ 5% of Baseline Body Weight at 72 Weeks (Yes/No) Missing	5.0 Percentage of participants	9.0 Percentage of participants	6.1 Percentage of participants	5.0 Percentage of participants

SECONDARY outcome

Timeframe: Week 72

Population: Full analysis set included all randomised participants.

Pentage of participants with weight loss of ≥ 10% of baseline body weight at 72 weeks is presented. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death. In the below table, 'Yes' infers percentage of participants who have achieved ≥ 10% weight loss; 'No' infers percentage of participants who have not achieved ≥ 10% weight loss at 72 weeks and 'Missing' refers to percentage of participants with data missing due to different reasons (lost to follow-up, withdrawal).

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=80 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=78 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=82 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=80 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Percentage of Participants With Weight Loss of ≥ 10% of Baseline Body Weight at 72 Weeks (Yes/No) Yes	17.5 Percentage of participants	38.5 Percentage of participants	59.8 Percentage of participants	2.5 Percentage of participants
Percentage of Participants With Weight Loss of ≥ 10% of Baseline Body Weight at 72 Weeks (Yes/No) No	77.5 Percentage of participants	52.6 Percentage of participants	34.1 Percentage of participants	92.5 Percentage of participants
Percentage of Participants With Weight Loss of ≥ 10% of Baseline Body Weight at 72 Weeks (Yes/No) Missing	5.0 Percentage of participants	9.0 Percentage of participants	6.1 Percentage of participants	5.0 Percentage of participants

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Full analysis set included all randomised participants. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in body weight from baseline to week 72 is presented. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=76 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=71 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=77 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=76 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Body Weight	-4.8 Kilograms Standard Deviation 6.0	-9.4 Kilograms Standard Deviation 9.2	-12.3 Kilograms Standard Deviation 8.6	-1.0 Kilograms Standard Deviation 4.9

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Full analysis set included all randomised participants. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in waist circumference from baseline to week 72 is presented. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=76 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=69 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=77 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=75 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Waist Circumference	-3.9 Centimeters Standard Deviation 6.3	-7.1 Centimeters Standard Deviation 8.9	-11.4 Centimeters Standard Deviation 9.3	-1.7 Centimeters Standard Deviation 6.2

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Full analysis set included all randomised participants.Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in BMI from baseline to week 72 is presented. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=76 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=71 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=77 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=76 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Body Mass Index (BMI)	-1.8 Kilograms per square meter Standard Deviation 2.2	-3.5 Kilograms per square meter Standard Deviation 3.4	-4.6 Kilograms per square meter Standard Deviation 3.3	-0.3 Kilograms per square meter Standard Deviation 1.8

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Full analysis set included all randomised participants. Overall number of participants analysed = Number of participants with type 2 diabetes who contributed to the analysis.

Change in HbA1c (measured as percentage point of HbA1c) from baseline to week 72 is presented. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=46 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=45 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=47 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=47 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Glycosylated Haemoglobin (HbA1c) (%-Point)	-0.7 Percentage point of HbA1c Standard Deviation 1.1	-1.2 Percentage point of HbA1c Standard Deviation 0.9	-1.2 Percentage point of HbA1c Standard Deviation 1.0	-0.0 Percentage point of HbA1c Standard Deviation 1.0

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Full analysis set included all randomised participants. Overall number of participants analysed = Number of participants with type 2 diabetes who contributed to the analysis.

Change in HbA1c from baseline to week 72 is presented. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=46 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=45 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=47 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=47 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in HbA1c (Millimoles Per Mole)	-7.9 millimoles per mole Standard Deviation 12.2	-12.8 millimoles per mole Standard Deviation 9.5	-12.8 millimoles per mole Standard Deviation 11.3	-0.3 millimoles per mole Standard Deviation 10.7

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Full analysis set included all randomised participants. Overall number of participants analysed = Number of participants with type 2 diabetes who contributed to the analysis.

Change in FPG from baseline to week 72 is presented. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=45 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=44 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=47 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=48 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Fasting Plasma Glucose (FPG)	-1.39 Millimoles per liter Standard Deviation 2.53	-2.17 Millimoles per liter Standard Deviation 1.82	-2.09 Millimoles per liter Standard Deviation 2.68	-0.34 Millimoles per liter Standard Deviation 2.72

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Full analysis set included all randomised participants. Overall number of participants analysed = Number of participants with type 2 diabetes who contributed to the analysis.

Change in fasting glucagon (measured as picograms per milliliter) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=45 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=45 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=47 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=47 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Fasting Glucagon	0.78 Ratio of glucagon Geometric Coefficient of Variation 76.8	0.65 Ratio of glucagon Geometric Coefficient of Variation 94.8	0.63 Ratio of glucagon Geometric Coefficient of Variation 100.4	1.04 Ratio of glucagon Geometric Coefficient of Variation 80.8

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Full analysis set included all randomised participants.Overall number of participants analysed = Number of participants with type 2 diabetes who contributed to the analysis.

Change in HOMA-IR is presented as ratio to baseline. HOMA-IR was calculated as: Insulin resistance (%) = fasting plasma glucose \[mmol/L\] x fasting insulin \[mmol/L\]/ 22.5. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=42 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=43 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=44 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=45 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Homeostatic Model Assessment - Insulin Resistance (HOMA-IR)	0.77 Ratio of HOMA-IR Geometric Coefficient of Variation 62.2	0.60 Ratio of HOMA-IR Geometric Coefficient of Variation 77.6	0.58 Ratio of HOMA-IR Geometric Coefficient of Variation 94.6	0.81 Ratio of HOMA-IR Geometric Coefficient of Variation 127.5

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Full analysis set included all randomised participants.Overall number of participants analysed = Number of participants who contributed to the analysis.

Blood pressure was measured in a sitting position after 5 minutes of rest. Change in DBP from baseline to week 72 is presented. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=76 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=70 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=77 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=76 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Diastolic Blood Pressure (DBP)	0 Millimeters of mercury Standard Deviation 10	-2 Millimeters of mercury Standard Deviation 11	-2 Millimeters of mercury Standard Deviation 9	-1 Millimeters of mercury Standard Deviation 10

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Full analysis set included all randomised participants. Overall number of participants analysed = Number of participants who contributed to the analysis.

Blood pressure was measured in a sitting position after 5 minutes of rest. Change in SBP from baseline to week 72 is presented. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=76 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=70 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=77 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=76 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Systolic Blood Pressure (SBP)	-2 Millimeters of mercury Standard Deviation 16	-7 Millimeters of mercury Standard Deviation 18	-6 Millimeters of mercury Standard Deviation 16	-2 Millimeters of mercury Standard Deviation 15

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Full analysis set included all randomised participants.Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in total cholesterol (measured as millimoles per liter) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=75 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=68 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=77 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=75 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Total Cholesterol	0.98 Ratio of total cholesterol Geometric Coefficient of Variation 17.1	1.00 Ratio of total cholesterol Geometric Coefficient of Variation 20.3	0.93 Ratio of total cholesterol Geometric Coefficient of Variation 15.7	0.93 Ratio of total cholesterol Geometric Coefficient of Variation 18.8

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Full analysis set included all randomised participants. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in LDL cholesterol (measured as millimoles per liter) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=73 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=68 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=77 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=75 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Low Density Lipoprotein (LDL) Cholesterol	0.96 Ratio of LDL cholesterol Geometric Coefficient of Variation 22.9	1.01 Ratio of LDL cholesterol Geometric Coefficient of Variation 34.9	0.92 Ratio of LDL cholesterol Geometric Coefficient of Variation 25.5	0.90 Ratio of LDL cholesterol Geometric Coefficient of Variation 30.7

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Full analysis set included all randomised participants. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in HDL cholesterol (measured as millimoles per liter) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=74 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=68 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=77 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=75 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in High Density Lipoprotein (HDL) Cholesterol	1.04 Ratio of HDL cholesterol Geometric Coefficient of Variation 16.1	1.05 Ratio of HDL cholesterol Geometric Coefficient of Variation 12.9	1.09 Ratio of HDL cholesterol Geometric Coefficient of Variation 16.4	1.01 Ratio of HDL cholesterol Geometric Coefficient of Variation 12.9

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Full analysis set included all randomised participants. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in VLDL cholesterol (measured as millimoles per liter) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=73 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=68 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=77 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=75 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Very Low Density Lipoprotein (VLDL) Cholesterol	0.89 Ratio of VLDL cholesterol Geometric Coefficient of Variation 31.9	0.90 Ratio of VLDL cholesterol Geometric Coefficient of Variation 36.1	0.74 Ratio of VLDL cholesterol Geometric Coefficient of Variation 38.2	0.93 Ratio of VLDL cholesterol Geometric Coefficient of Variation 36.7

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Full analysis set included all randomised participants. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in triglycerides (measured as millimoles per liter) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=74 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=68 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=77 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=75 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Triglycerides	0.88 Ratio of triglycerides Geometric Coefficient of Variation 34.1	0.89 Ratio of triglycerides Geometric Coefficient of Variation 37.6	0.73 Ratio of triglycerides Geometric Coefficient of Variation 41.4	0.95 Ratio of triglycerides Geometric Coefficient of Variation 36.9

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Full analysis set included all randomised participants. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in free fatty acids (measured as millimoles per liter) is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=72 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=68 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=74 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=72 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Free Fatty Acids	0.83 Ratio of free fatty acids Geometric Coefficient of Variation 54.8	0.92 Ratio of free fatty acids Geometric Coefficient of Variation 73.2	0.72 Ratio of free fatty acids Geometric Coefficient of Variation 80.8	1.05 Ratio of free fatty acids Geometric Coefficient of Variation 75.9

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Full analysis set included all randomised participants. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in hsCRP (measured as milligram per liter) from baseline to week 72 is presented as ratio to baseline. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=76 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=71 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=77 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=75 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in High Sensitivity C-reactive Protein (hsCRP)	0.78 Ratio of hsCRP Geometric Coefficient of Variation 114.6	0.50 Ratio of hsCRP Geometric Coefficient of Variation 124.1	0.41 Ratio of hsCRP Geometric Coefficient of Variation 114.6	0.91 Ratio of hsCRP Geometric Coefficient of Variation 85.8

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Full analysis set included all randomised participants. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in SF-36 score from baseline to week 72 is presented. SF-36 measures participant's overall health related quality of life (HRQoL). It is a 36-item generic measure of health status and yields 2 summary scores for physical health and mental health, and 8 domain scores (physical functioning, role functioning, bodily pain, general health, vitality, social functioning, role emotional, mental health). The scores 0-100 (where higher scores indicates a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of scores in the 2009 U.S. general population. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=80 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=78 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=82 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=80 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Short Form 36 (SF-36) Score Mental component sum	2.2 Scores on a scale Standard Deviation 8.5	0.6 Scores on a scale Standard Deviation 9.2	1.2 Scores on a scale Standard Deviation 9.5	-0.4 Scores on a scale Standard Deviation 8.9
Change in Short Form 36 (SF-36) Score Physical component sum	2.1 Scores on a scale Standard Deviation 7.0	1.1 Scores on a scale Standard Deviation 7.3	3.9 Scores on a scale Standard Deviation 7.1	-0.1 Scores on a scale Standard Deviation 8.3
Change in Short Form 36 (SF-36) Score Physical functioning	1.8 Scores on a scale Standard Deviation 7.8	2.0 Scores on a scale Standard Deviation 7.3	2.8 Scores on a scale Standard Deviation 7.8	-0.4 Scores on a scale Standard Deviation 8.2
Change in Short Form 36 (SF-36) Score Role functioning	2.1 Scores on a scale Standard Deviation 6.9	0.5 Scores on a scale Standard Deviation 9.3	2.2 Scores on a scale Standard Deviation 8.1	-0.3 Scores on a scale Standard Deviation 9.4
Change in Short Form 36 (SF-36) Score Bodily pain	1.3 Scores on a scale Standard Deviation 10.9	1.2 Scores on a scale Standard Deviation 10.1	3.4 Scores on a scale Standard Deviation 7.9	-1.3 Scores on a scale Standard Deviation 10.2
Change in Short Form 36 (SF-36) Score General health	7.2 Scores on a scale Standard Deviation 14.8	2.3 Scores on a scale Standard Deviation 17.8	9.0 Scores on a scale Standard Deviation 17.4	4.3 Scores on a scale Standard Deviation 16.5
Change in Short Form 36 (SF-36) Score Vitality	2.3 Scores on a scale Standard Deviation 8.6	0.6 Scores on a scale Standard Deviation 9.4	4.6 Scores on a scale Standard Deviation 9.8	-0.2 Scores on a scale Standard Deviation 10.1
Change in Short Form 36 (SF-36) Score Social functioning	3.7 Scores on a scale Standard Deviation 9.0	-0.1 Scores on a scale Standard Deviation 9.9	2.2 Scores on a scale Standard Deviation 9.4	-1.6 Scores on a scale Standard Deviation 8.3
Change in Short Form 36 (SF-36) Score Role emotional	2.2 Scores on a scale Standard Deviation 8.9	0.6 Scores on a scale Standard Deviation 9.1	0.5 Scores on a scale Standard Deviation 9.5	-0.3 Scores on a scale Standard Deviation 8.5
Change in Short Form 36 (SF-36) Score Mental health	1.2 Scores on a scale Standard Deviation 8.9	1.5 Scores on a scale Standard Deviation 8.2	1.3 Scores on a scale Standard Deviation 9.5	-0.2 Scores on a scale Standard Deviation 9.7

SECONDARY outcome

Timeframe: From week 0 to week 79

Population: Safety analysis set included all participants who received at least one dose of randomised treatment.

An adverse event (AE) was any untoward medical occurrence in a clinical trial participant administered or using a medicinal product, whether or not considered related to the medicinal product or usage. All AEs reported here are TEAEs. TEAE is defined as an event that had onset date during the on-treatment period. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half lives of semaglutide); 2) end of the in-trial period.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=80 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=78 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=81 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=80 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Number of Treatment-emergent Adverse Events (TEAEs)	525 events	577 events	511 events	445 events

SECONDARY outcome

Timeframe: From week 0 to week 79

Population: Safety analysis set included all participants who received at least one dose of randomised treatment. Overall number of participants analysed = Number of participants with type 2 diabetes who contributed to the analysis.

Hypoglycaemic episode (blood glucose less than or equal to (\<=) 3.9 mmol/L (70 mg/dL) Or greater than (\>) 3.9 mmol/L (70 mg/dL) occurring in conjunction with hypoglycaemic symptoms) is defined as treatment emergent if the onset of the episode occurs during the on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=49 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=51 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=49 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=50 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Number of Treatment-emergent Hypoglycaemic Episodes	54 episodes	30 episodes	66 episodes	18 episodes

SECONDARY outcome

Timeframe: From week 0 to week 79

Population: Safety analysis set included all participants who received at least one dose of randomised treatment. Overall number of participants analysed = Number of participants with type 2 diabetes who contributed to the analysis.

Severe or BG confirmed symptomatic hypoglycaemia: episode, severe as per american diabetes association (ADA) classification or BG confirmed by plasma glucose value \< 3.1 mmol/L(56mg/dL) with symptoms along with hypoglycaemia. Severe hypoglycaemia: episode requiring assistance of other person to actively administer carbohydrate, glucagon, or take corrective actions. Plasma glucose concentrations may not be available during event, but neurological recovery following return of plasma glucose to normal is sufficient evidence that event was induced by low plasma glucose concentration. Hypoglycaemic episode is treatment emergent if onset of it occurs during on-treatment period: period starting on day of first administration of trial product and ending on day of last dose of trial product+7 days; except for evaluation of AEs; hypoglycaemic episodes for which period ended on date of whatever came first:last dose of trial product + 49 days (7 half-lives of semaglutide); end of in-trial period.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=49 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=51 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=49 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=50 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Number of Treatment-emergent Severe or Blood Glucose (BG)-Confirmed Symptomatic Hypoglycaemic Episodes	3 episodes	5 episodes	17 episodes	2 episodes

SECONDARY outcome

Timeframe: From week 0 to week 79

Population: Safety analysis set included all participants who received at least one dose of randomised treatment. Overall number of participants analysed = Number of participants with type 2 diabetes who contributed to the analysis.

Severe hypoglycaemia: An episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. Plasma glucose concentrations may not be available during an event, but neurological recovery following the return of plasma glucose to normal is considered sufficient evidence that the event was induced by a low plasma glucose concentration. Hypoglycaemic episode is defined as treatment emergent if the onset of the episode occurs during the on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=49 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=51 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=49 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=50 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Number of Treatment-emergent Severe Hypoglycaemic Episodes	2 episodes	2 episodes	0 episodes	0 episodes

SECONDARY outcome

Timeframe: From week 0 to week 79

Population: Safety analysis set included all participants who received at least one dose of randomised treatment.

Number of participants discontinuing treatment due to gastrointestinal adverse events is presented. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=80 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=78 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=81 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=80 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Number of Participants Discontinuing Treatment Due to Gastrointestinal Adverse Events	1 Participants	6 Participants	2 Participants	0 Participants

SECONDARY outcome

Timeframe: From week 0 to week 79

Population: Safety analysis set included all participants who received at least one dose of randomised treatment.

Number of participants with occurrence of anti-semaglutide antibodies during and after 72 weeks treatment is presented. In the below table, 'Yes' infers number of participants with occurrence of anti-semaglutide antibodies and 'No' infers number of participants without anti-semaglutide antibodies during and after 72 weeks treatment. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=80 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=78 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=81 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Number of Participants With Occurrence of Anti-semaglutide Antibodies During and After 72 Weeks Treatment (Yes/No) Yes	4 Participants	1 Participants	2 Participants	—
Number of Participants With Occurrence of Anti-semaglutide Antibodies During and After 72 Weeks Treatment (Yes/No) No	76 Participants	77 Participants	79 Participants	—

SECONDARY outcome

Timeframe: From week 0 to week 79

Population: Safety analysis set included all participants who received at least one dose of randomised treatment.

Number of participants with anti-semaglutide antibodies with in vitro neutralising effect during and after 72 weeks treatment is presented. In the below table, 'Yes' infers number of participants with anti-semaglutide antibodies with in vitro neutralising effect and 'No' infers number of participants without anti-semaglutide antibodies with in vitro neutralising effect during and after 72 weeks treatment. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=80 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=78 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=81 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Number of Participants With Anti-semaglutide Antibodies With in Vitro Neutralising Effect During and After 72 Weeks Treatment (Yes/No) Yes	0 Participants	0 Participants	0 Participants	—
Number of Participants With Anti-semaglutide Antibodies With in Vitro Neutralising Effect During and After 72 Weeks Treatment (Yes/No) No	80 Participants	78 Participants	81 Participants	—

SECONDARY outcome

Timeframe: From week 0 to week 79

Population: Safety analysis set included all participants who received at least one dose of randomised treatment.

Number of participants with anti-semaglutide binding antibodies cross reacting with native glucagon-like peptide-1 (GLP-1) during and after 72 weeks treatment is presented. In the below table, 'Yes' infers number of participants with anti-semaglutide antibodies cross reacting with native GLP-1 and 'No' infers number of participants without anti-semaglutide antibodies cross reacting with native GLP-1 during and after 72 weeks treatment. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=80 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=78 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=81 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Number of Participants With Anti-semaglutide Binding Antibodies Cross Reacting With Native GLP-1 During and After 72 Weeks Treatment (Yes/No) Yes	4 Participants	0 Participants	2 Participants	—
Number of Participants With Anti-semaglutide Binding Antibodies Cross Reacting With Native GLP-1 During and After 72 Weeks Treatment (Yes/No) No	76 Participants	78 Participants	79 Participants	—

SECONDARY outcome

Timeframe: From week 0 to week 79

Population: Safety analysis set included all participants who received at least one dose of randomised treatment.

Number of participants with cross-reacting anti-semaglutide binding antibodies with in vitro neutralising effect to native GLP-1 during and after 72 weeks treatment is presented. In the below table, 'Yes' infers number of participants with cross-reacting anti-semaglutide binding antibodies with in vitro neutralising effect to native GLP-1 and 'No' infers number of participants without cross-reacting anti-semaglutide binding antibodies with in vitro neutralising effect to native GLP-1 during and after 72 weeks treatment. The endpoint was evaluated based on the data from in-trial period which started on the date of the randomisation visit and ended on the first of the following dates (both inclusive): 1) follow-up visit (Week 79); 2) withdrawal of consent; 3) last contact with participant (for participants lost to follow-up); 4) death.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=80 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=78 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=81 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Number of Participants With Cross-reacting Anti-semaglutide Binding Antibodies With in Vitro Neutralising Effect to Native GLP-1 During and After 72 Weeks Treatment (Yes/No) Yes	0 Participants	0 Participants	0 Participants	—
Number of Participants With Cross-reacting Anti-semaglutide Binding Antibodies With in Vitro Neutralising Effect to Native GLP-1 During and After 72 Weeks Treatment (Yes/No) No	80 Participants	78 Participants	81 Participants	—

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Safety analysis set included all participants who received at least one dose of randomised treatment. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in pulse from baseline to week 72 is presented. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=73 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=63 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=72 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=71 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Pulse From Baseline to Week 72	2.2 beats per minute (bpm) Standard Deviation 10.9	2.1 beats per minute (bpm) Standard Deviation 9.0	0.9 beats per minute (bpm) Standard Deviation 9.6	-0.3 beats per minute (bpm) Standard Deviation 9.1

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Safety analysis set included all participants who received at least one dose of randomised treatment. Overall number of participants analysed = Number of participants who contributed to the analysis.

A 12-lead ECG was performed at baseline (week 0) and week 72 and categorised as normal, abnormal and not clinically significant (abnormal NCS) or abnormal and clinically significant (abnormal CS). Percentage of participants in each ECG category at week 0 and week 72 are presented. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=80 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=78 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=81 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=80 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Percentage of Participants With Change in Electrocardiogram (ECG) Week 0: Normal	58.8 Percentage of participants	60.3 Percentage of participants	66.7 Percentage of participants	63.8 Percentage of participants
Percentage of Participants With Change in Electrocardiogram (ECG) Week 0: Abnormal NCS	41.3 Percentage of participants	39.7 Percentage of participants	32.1 Percentage of participants	36.3 Percentage of participants
Percentage of Participants With Change in Electrocardiogram (ECG) Week 0: Abnormal CS	0.0 Percentage of participants	0.0 Percentage of participants	1.2 Percentage of participants	0.0 Percentage of participants
Percentage of Participants With Change in Electrocardiogram (ECG) Week 72: Normal	64.9 Percentage of participants	65.1 Percentage of participants	74.6 Percentage of participants	60.0 Percentage of participants
Percentage of Participants With Change in Electrocardiogram (ECG) Week 72: Abnormal NCS	35.1 Percentage of participants	34.9 Percentage of participants	23.9 Percentage of participants	38.6 Percentage of participants
Percentage of Participants With Change in Electrocardiogram (ECG) Week 72: Abnormal CS	0.0 Percentage of participants	0.0 Percentage of participants	1.4 Percentage of participants	1.4 Percentage of participants

SECONDARY outcome

Timeframe: Week -6, week 72

Population: Safety analysis set included all participants who received at least one dose of randomised treatment. Overall number of participants analysed = Number of participants who contributed to the analysis.

Percentage of participants with change in physical examination (cardiovascular system) from week -6 to week 72 is presented. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=80 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=78 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=81 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=80 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Percentage of Participants With Change in Physical Examination: Cardiovascular System Week -6: Normal	87.5 Percentage of participants	93.6 Percentage of participants	92.6 Percentage of participants	92.5 Percentage of participants
Percentage of Participants With Change in Physical Examination: Cardiovascular System Week -6: Abnormal NCS	11.3 Percentage of participants	5.1 Percentage of participants	7.4 Percentage of participants	6.3 Percentage of participants
Percentage of Participants With Change in Physical Examination: Cardiovascular System Week -6: Abnormal CS	1.3 Percentage of participants	1.3 Percentage of participants	0.0 Percentage of participants	1.3 Percentage of participants
Percentage of Participants With Change in Physical Examination: Cardiovascular System Week 72: Normal	87.8 Percentage of participants	96.9 Percentage of participants	94.4 Percentage of participants	90.1 Percentage of participants
Percentage of Participants With Change in Physical Examination: Cardiovascular System Week 72: Abnormal NCS	12.2 Percentage of participants	3.1 Percentage of participants	5.6 Percentage of participants	8.5 Percentage of participants
Percentage of Participants With Change in Physical Examination: Cardiovascular System Week 72: Abnormal CS	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	1.4 Percentage of participants

SECONDARY outcome

Timeframe: Week -6, week 72

Population: Safety analysis set included all participants who received at least one dose of randomised treatment. Overall number of participants analysed = Number of participants who contributed to the analysis.

Percentage of participants with change in physical examination (central and peripheral nervous system) from week -6 to week 72 is presented. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=80 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=77 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=79 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=80 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Percentage of Participants With Change in Physical Examination: Central and Peripheral Nervous System Week -6: Abnormal CS	2.5 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	1.3 Percentage of participants
Percentage of Participants With Change in Physical Examination: Central and Peripheral Nervous System Week 72: Normal	94.6 Percentage of participants	93.7 Percentage of participants	98.6 Percentage of participants	92.9 Percentage of participants
Percentage of Participants With Change in Physical Examination: Central and Peripheral Nervous System Week 72: Abnormal NCS	5.4 Percentage of participants	4.8 Percentage of participants	1.4 Percentage of participants	7.1 Percentage of participants
Percentage of Participants With Change in Physical Examination: Central and Peripheral Nervous System Week 72: Abnormal CS	0.0 Percentage of participants	1.6 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants
Percentage of Participants With Change in Physical Examination: Central and Peripheral Nervous System Week -6: Normal	92.5 Percentage of participants	94.8 Percentage of participants	98.7 Percentage of participants	95.0 Percentage of participants
Percentage of Participants With Change in Physical Examination: Central and Peripheral Nervous System Week -6: Abnormal NCS	5.0 Percentage of participants	5.2 Percentage of participants	1.3 Percentage of participants	3.8 Percentage of participants

SECONDARY outcome

Timeframe: Week -6, week 72

Population: Safety analysis set included all participants who received at least one dose of randomised treatment. Overall number of participants analysed = Number of participants who contributed to the analysis.

Percentage of participants with change in physical examination (gastrointestinal system including mouth) from week -6 to week 72 is presented. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=80 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=77 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=81 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=80 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Percentage of Participants With Change in Physical Examination: Gastrointestinal System Including Mouth Week -6: Normal	82.5 Percentage of participants	83.1 Percentage of participants	84.0 Percentage of participants	86.3 Percentage of participants
Percentage of Participants With Change in Physical Examination: Gastrointestinal System Including Mouth Week -6: Abnormal NCS	13.8 Percentage of participants	15.6 Percentage of participants	16.0 Percentage of participants	12.5 Percentage of participants
Percentage of Participants With Change in Physical Examination: Gastrointestinal System Including Mouth Week -6: Abnormal CS	3.8 Percentage of participants	1.3 Percentage of participants	0.0 Percentage of participants	1.3 Percentage of participants
Percentage of Participants With Change in Physical Examination: Gastrointestinal System Including Mouth Week 72: Normal	89.2 Percentage of participants	81.0 Percentage of participants	87.5 Percentage of participants	84.5 Percentage of participants
Percentage of Participants With Change in Physical Examination: Gastrointestinal System Including Mouth Week 72: Abnormal NCS	10.8 Percentage of participants	19.0 Percentage of participants	12.5 Percentage of participants	14.1 Percentage of participants
Percentage of Participants With Change in Physical Examination: Gastrointestinal System Including Mouth Week 72: Abnormal CS	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	1.4 Percentage of participants

SECONDARY outcome

Timeframe: Week -6, week 72

Population: Safety analysis set included all participants who received at least one dose of randomised treatment. Overall number of participants analysed = Number of participants who contributed to the analysis.

Percentage of participants with change in physical examination (general appearance) from week -6 to week 72 is presented. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=80 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=78 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=81 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=80 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Percentage of Participants With Change in Physical Examination: General Appearance Week -6: Abnormal NCS	16.3 Percentage of participants	12.8 Percentage of participants	21.0 Percentage of participants	20.0 Percentage of participants
Percentage of Participants With Change in Physical Examination: General Appearance Week -6: Normal	83.8 Percentage of participants	85.9 Percentage of participants	79.0 Percentage of participants	80.0 Percentage of participants
Percentage of Participants With Change in Physical Examination: General Appearance Week -6: Abnormal CS	0.0 Percentage of participants	1.3 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants
Percentage of Participants With Change in Physical Examination: General Appearance Week 72: Normal	83.8 Percentage of participants	90.6 Percentage of participants	90.3 Percentage of participants	76.1 Percentage of participants
Percentage of Participants With Change in Physical Examination: General Appearance Week 72: Abnormal NCS	16.2 Percentage of participants	6.3 Percentage of participants	9.7 Percentage of participants	23.9 Percentage of participants
Percentage of Participants With Change in Physical Examination: General Appearance Week 72: Abnormal CS	0.0 Percentage of participants	3.1 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants

SECONDARY outcome

Timeframe: Week -6, week 72

Population: Safety analysis set included all participants who received at least one dose of randomised treatment. Overall number of participants analysed = Number of participants who contributed to the analysis.

Percentage of participants with change in physical examination (head, ears, eyes, nose, throat, neck) from week -6 to week 72 is presented. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=80 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=77 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=80 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=80 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Percentage of Participants With Change in Physical Examination: Head, Ears, Eyes, Nose, Throat, Neck Week -6: Normal	97.5 Percentage of participants	94.8 Percentage of participants	98.8 Percentage of participants	97.5 Percentage of participants
Percentage of Participants With Change in Physical Examination: Head, Ears, Eyes, Nose, Throat, Neck Week -6: Abnormal NCS	2.5 Percentage of participants	5.2 Percentage of participants	1.3 Percentage of participants	2.5 Percentage of participants
Percentage of Participants With Change in Physical Examination: Head, Ears, Eyes, Nose, Throat, Neck Week -6: Abnormal CS	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants
Percentage of Participants With Change in Physical Examination: Head, Ears, Eyes, Nose, Throat, Neck Week 72: Normal	94.5 Percentage of participants	96.8 Percentage of participants	98.6 Percentage of participants	98.6 Percentage of participants
Percentage of Participants With Change in Physical Examination: Head, Ears, Eyes, Nose, Throat, Neck Week 72: Abnormal NCS	4.1 Percentage of participants	3.2 Percentage of participants	1.4 Percentage of participants	0.0 Percentage of participants
Percentage of Participants With Change in Physical Examination: Head, Ears, Eyes, Nose, Throat, Neck Week 72: Abnormal CS	1.4 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	1.4 Percentage of participants

SECONDARY outcome

Timeframe: Week -6, week 72

Population: Safety analysis set included all participants who received at least one dose of randomised treatment. Overall number of participants analysed = Number of participants who contributed to the analysis.

Percentage of participants with change in physical examination (lymph node palpation) from week -6 to week 72 is presented. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=80 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=77 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=78 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=80 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Percentage of Participants With Change in Physical Examination: Lymph Node Palpation Week -6: Normal	100.0 Percentage of participants	98.7 Percentage of participants	100.0 Percentage of participants	100.0 Percentage of participants
Percentage of Participants With Change in Physical Examination: Lymph Node Palpation Week -6: Abnormal NCS	0.0 Percentage of participants	1.3 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants
Percentage of Participants With Change in Physical Examination: Lymph Node Palpation Week -6: Abnormal CS	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants
Percentage of Participants With Change in Physical Examination: Lymph Node Palpation Week 72: Normal	100.0 Percentage of participants	100.0 Percentage of participants	100.0 Percentage of participants	100.0 Percentage of participants
Percentage of Participants With Change in Physical Examination: Lymph Node Palpation Week 72: Abnormal NCS	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants
Percentage of Participants With Change in Physical Examination: Lymph Node Palpation Week 72: Abnormal CS	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants

SECONDARY outcome

Timeframe: Week -6, week 72

Population: Safety analysis set included all participants who received at least one dose of randomised treatment. Overall number of participants analysed = Number of participants who contributed to the analysis.

Percentage of participants with change in physical examination (musculoskeletal system) from week -6 to week 72 is presented. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=80 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=77 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=79 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=80 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Percentage of Participants With Change in Physical Examination: Musculoskeletal System Week -6: Normal	95.0 Percentage of participants	96.1 Percentage of participants	94.9 Percentage of participants	95.0 Percentage of participants
Percentage of Participants With Change in Physical Examination: Musculoskeletal System Week -6: Abnormal NCS	3.8 Percentage of participants	3.9 Percentage of participants	5.1 Percentage of participants	3.8 Percentage of participants
Percentage of Participants With Change in Physical Examination: Musculoskeletal System Week -6: Abnormal CS	1.3 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	1.3 Percentage of participants
Percentage of Participants With Change in Physical Examination: Musculoskeletal System Week 72: Normal	94.6 Percentage of participants	96.8 Percentage of participants	100.0 Percentage of participants	95.8 Percentage of participants
Percentage of Participants With Change in Physical Examination: Musculoskeletal System Week 72: Abnormal NCS	5.4 Percentage of participants	3.2 Percentage of participants	0.0 Percentage of participants	4.2 Percentage of participants
Percentage of Participants With Change in Physical Examination: Musculoskeletal System Week 72: Abnormal CS	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants

SECONDARY outcome

Timeframe: Week -6, week 72

Population: Safety analysis set included all participants who received at least one dose of randomised treatment. Overall number of participants analysed = Number of participants who contributed to the analysis.

Percentage of participants with change in physical examination (respiratory system) from week -6 to week 72 is presented. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=80 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=78 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=81 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=80 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Percentage of Participants With Change in Physical Examination: Respiratory System Week -6: Abnormal CS	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants
Percentage of Participants With Change in Physical Examination: Respiratory System Week 72: Normal	98.6 Percentage of participants	96.9 Percentage of participants	98.6 Percentage of participants	98.6 Percentage of participants
Percentage of Participants With Change in Physical Examination: Respiratory System Week -6: Normal	100.0 Percentage of participants	100.0 Percentage of participants	100.0 Percentage of participants	97.5 Percentage of participants
Percentage of Participants With Change in Physical Examination: Respiratory System Week -6: Abnormal NCS	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	2.5 Percentage of participants
Percentage of Participants With Change in Physical Examination: Respiratory System Week 72: Abnormal NCS	0.0 Percentage of participants	3.1 Percentage of participants	1.4 Percentage of participants	1.4 Percentage of participants
Percentage of Participants With Change in Physical Examination: Respiratory System Week 72: Abnormal CS	1.4 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants

SECONDARY outcome

Timeframe: Week -6, week 72

Population: Safety analysis set included all participants who received at least one dose of randomised treatment. Overall number of participants analysed = Number of participants who contributed to the analysis.

Percentage of participants with change in physical examination (skin) from week -6 to week 72 is presented. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=80 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=78 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=81 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=80 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Percentage of Participants With Change in Physical Examination: Skin Week -6: Normal	96.3 Percentage of participants	92.3 Percentage of participants	85.2 Percentage of participants	90.0 Percentage of participants
Percentage of Participants With Change in Physical Examination: Skin Week -6: Abnormal NCS	2.5 Percentage of participants	6.4 Percentage of participants	13.6 Percentage of participants	10.0 Percentage of participants
Percentage of Participants With Change in Physical Examination: Skin Week -6: Abnormal CS	1.3 Percentage of participants	1.3 Percentage of participants	1.2 Percentage of participants	0.0 Percentage of participants
Percentage of Participants With Change in Physical Examination: Skin Week 72: Normal	94.6 Percentage of participants	87.5 Percentage of participants	90.0 Percentage of participants	88.7 Percentage of participants
Percentage of Participants With Change in Physical Examination: Skin Week 72: Abnormal NCS	4.1 Percentage of participants	10.9 Percentage of participants	8.6 Percentage of participants	11.3 Percentage of participants
Percentage of Participants With Change in Physical Examination: Skin Week 72: Abnormal CS	1.4 Percentage of participants	1.6 Percentage of participants	1.4 Percentage of participants	0.0 Percentage of participants

SECONDARY outcome

Timeframe: Week -6, week 72

Population: Safety analysis set included all participants who received at least one dose of randomised treatment. Overall number of participants analysed = Number of participants who contributed to the analysis.

Percentage of participants with change in physical examination (thyroid gland) from week -6 to week 72 is presented. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=80 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=77 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=80 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=80 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Percentage of Participants With Change in Physical Examination: Thyroid Gland Week -6: Normal	88.8 Percentage of participants	97.4 Percentage of participants	97.5 Percentage of participants	98.8 Percentage of participants
Percentage of Participants With Change in Physical Examination: Thyroid Gland Week -6: Abnormal NCS	10.0 Percentage of participants	2.6 Percentage of participants	2.5 Percentage of participants	0.0 Percentage of participants
Percentage of Participants With Change in Physical Examination: Thyroid Gland Week -6: Abnormal CS	1.3 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	1.3 Percentage of participants
Percentage of Participants With Change in Physical Examination: Thyroid Gland Week 72: Normal	94.6 Percentage of participants	98.4 Percentage of participants	97.1 Percentage of participants	98.6 Percentage of participants
Percentage of Participants With Change in Physical Examination: Thyroid Gland Week 72: Abnormal NCS	5.4 Percentage of participants	1.6 Percentage of participants	2.9 Percentage of participants	1.4 Percentage of participants
Percentage of Participants With Change in Physical Examination: Thyroid Gland Week 72: Abnormal CS	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants	0.0 Percentage of participants

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Safety analysis set included all participants who received at least one dose of randomised treatment. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in haematocrit from baseline to week 72 is presented. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=71 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=59 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=70 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=68 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Haematocrit	-0.79 Percentage of haematocrit in blood Standard Deviation 3.14	-0.71 Percentage of haematocrit in blood Standard Deviation 2.77	-1.43 Percentage of haematocrit in blood Standard Deviation 3.50	-0.41 Percentage of haematocrit in blood Standard Deviation 3.53

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Safety analysis set included all participants who received at least one dose of randomised treatment. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in haemoglobin from baseline to week 72 is presented. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=71 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=59 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=70 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=68 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Haemoglobin (g/dL)	0.18 Grams per deciliter (g/dL) Standard Deviation 1.05	0.08 Grams per deciliter (g/dL) Standard Deviation 0.89	-0.07 Grams per deciliter (g/dL) Standard Deviation 0.98	0.21 Grams per deciliter (g/dL) Standard Deviation 1.08

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Safety analysis set included all participants who received at least one dose of randomised treatment. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in haemoglobin from baseline to week 72 is presented. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=71 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=59 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=70 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=68 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Haemoglobin (mmol/L)	0.11 millimoles per liter (mmol/L) Standard Deviation 0.65	0.05 millimoles per liter (mmol/L) Standard Deviation 0.55	-0.05 millimoles per liter (mmol/L) Standard Deviation 0.61	0.13 millimoles per liter (mmol/L) Standard Deviation 0.67

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Safety analysis set included all participants who received at least one dose of randomised treatment. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in leukocytes from baseline to week 72 is presented. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=71 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=59 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=70 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=68 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Leukocytes	0.489 10^9 cells per liter (10^9/L) Standard Deviation 1.564	0.260 10^9 cells per liter (10^9/L) Standard Deviation 1.343	-0.047 10^9 cells per liter (10^9/L) Standard Deviation 1.532	0.075 10^9 cells per liter (10^9/L) Standard Deviation 1.733

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Safety analysis set included all participants who received at least one dose of randomised treatment. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in thrombocytes from baseline to week 72 is presented. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=71 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=59 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=69 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=67 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Thrombocytes	8.8 10^9 cells per liter (10^9/L) Standard Deviation 46.9	14.6 10^9 cells per liter (10^9/L) Standard Deviation 34.8	9.0 10^9 cells per liter (10^9/L) Standard Deviation 44.9	0.3 10^9 cells per liter (10^9/L) Standard Deviation 43.7

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Safety analysis set included all participants who received at least one dose of randomised treatment. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in erythrocytes from baseline to week 72 is presented. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=71 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=59 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=70 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=68 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Erythrocytes	0.038 10^12 cells per liter (10^12/L) Standard Deviation 0.292	0.004 10^12 cells per liter (10^12/L) Standard Deviation 0.220	-0.034 10^12 cells per liter (10^12/L) Standard Deviation 0.334	0.054 10^12 cells per liter (10^12/L) Standard Deviation 0.314

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Safety analysis set included all participants who received at least one dose of randomised treatment. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in creatinine (measured as milligram per deciliter (mg/dL)) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=74 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=62 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=72 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=70 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Creatinine (mg/dL)	1.018 Ratio of creatinine Geometric Coefficient of Variation 30.70	1.069 Ratio of creatinine Geometric Coefficient of Variation 42.19	1.026 Ratio of creatinine Geometric Coefficient of Variation 35.17	1.021 Ratio of creatinine Geometric Coefficient of Variation 33.87

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Safety analysis set included all participants who received at least one dose of randomised treatment. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in creatinine (measured as micro mole per liter (umol/L)) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=74 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=62 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=72 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=70 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Creatinine (Umol/L)	1.018 Ratio of creatinine Geometric Coefficient of Variation 30.70	1.069 Ratio of creatinine Geometric Coefficient of Variation 42.19	1.026 Ratio of creatinine Geometric Coefficient of Variation 35.17	1.021 Ratio of creatinine Geometric Coefficient of Variation 33.87

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Safety analysis set included all participants who received at least one dose of randomised treatment. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in eGFR (measured as milliliter/minute/1.732 meter square (mL/min/1.73 m\^2)) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=74 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=62 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=72 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=70 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Estimated Glomerular Filtration Rate (eGFR)	0.976 Ratio of eGFR Geometric Coefficient of Variation 28.04	0.940 Ratio of eGFR Geometric Coefficient of Variation 40.47	0.973 Ratio of eGFR Geometric Coefficient of Variation 31.42	0.969 Ratio of eGFR Geometric Coefficient of Variation 31.24

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Safety analysis set included all participants who received at least one dose of randomised treatment. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in creatine kinase (measured as units per liter) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=74 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=62 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=72 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=70 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Creatine Kinase	0.975 Ratio of creatine kinase Geometric Coefficient of Variation 73.02	0.798 Ratio of creatine kinase Geometric Coefficient of Variation 77.96	0.825 Ratio of creatine kinase Geometric Coefficient of Variation 74.17	0.904 Ratio of creatine kinase Geometric Coefficient of Variation 76.04

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Safety analysis set included all participants who received at least one dose of randomised treatment. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in urea (measured as milli mole per liter) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=74 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=62 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=72 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=70 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Urea	1.018 Ratio of urea Geometric Coefficient of Variation 51.01	0.973 Ratio of urea Geometric Coefficient of Variation 52.30	1.042 Ratio of urea Geometric Coefficient of Variation 51.14	1.043 Ratio of urea Geometric Coefficient of Variation 52.30

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Safety analysis set included all participants who received at least one dose of randomised treatment. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in total bilirubin (measured as milligram per deciliter (mg/dL)) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=74 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=62 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=72 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=70 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Total Bilirubin (mg/dL)	0.978 Ratio of total bilirubin Geometric Coefficient of Variation 66.72	1.011 Ratio of total bilirubin Geometric Coefficient of Variation 70.66	0.949 Ratio of total bilirubin Geometric Coefficient of Variation 65.89	1.040 Ratio of total bilirubin Geometric Coefficient of Variation 67.36

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Safety analysis set included all participants who received at least one dose of randomised treatment. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in total bilirubin (measured as micromole per liter (umol/L)) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=74 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=62 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=72 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=70 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Total Bilirubin (Umol/L)	0.978 Ratio of total bilirubin Geometric Coefficient of Variation 66.72	1.011 Ratio of total bilirubin Geometric Coefficient of Variation 70.66	0.949 Ratio of total bilirubin Geometric Coefficient of Variation 65.89	1.040 Ratio of total bilirubin Geometric Coefficient of Variation 67.36

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Safety analysis set included all participants who received at least one dose of randomised treatment. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in alkaline phosphatase (measured as units per liter) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=74 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=62 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=72 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=70 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Alkaline Phosphatase	0.980 Ratio of alkaline phosphatase Geometric Coefficient of Variation 45.68	0.931 Ratio of alkaline phosphatase Geometric Coefficient of Variation 43.59	0.884 Ratio of alkaline phosphatase Geometric Coefficient of Variation 54.90	0.992 Ratio of alkaline phosphatase Geometric Coefficient of Variation 42.42

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Safety analysis set included all participants who received at least one dose of randomised treatment. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in ferritin (measured as microgram per liter) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=74 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=62 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=72 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=70 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Ferritin	0.660 Ratio of ferritin Geometric Coefficient of Variation 99.95	0.617 Ratio of ferritin Geometric Coefficient of Variation 88.70	0.603 Ratio of ferritin Geometric Coefficient of Variation 88.83	0.713 Ratio of ferritin Geometric Coefficient of Variation 96.91

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Safety analysis set included all participants who received at least one dose of randomised treatment. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in sodium (measured as milli equivalent per liter (mEq/L)) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=74 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=62 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=72 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=70 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Sodium (mEq/L)	0.999 Ratio of sodium Geometric Coefficient of Variation 12.23	1.000 Ratio of sodium Geometric Coefficient of Variation 12.13	1.002 Ratio of sodium Geometric Coefficient of Variation 11.68	1.002 Ratio of sodium Geometric Coefficient of Variation 12.91

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Safety analysis set included all participants who received at least one dose of randomised treatment. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in sodium (measured as milli mole per liter (mmol/L)) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=74 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=62 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=72 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=70 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Sodium (mmol/L)	0.999 Ratio of sodium Geometric Coefficient of Variation 12.23	1.000 Ratio of sodium Geometric Coefficient of Variation 12.13	1.002 Ratio of sodium Geometric Coefficient of Variation 11.68	1.002 Ratio of sodium Geometric Coefficient of Variation 12.91

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Safety analysis set included all participants who received at least one dose of randomised treatment. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in potassium (measured as mEq/L) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=74 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=61 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=72 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=69 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Potassium (mEq/L)	1.004 Ratio of potassium Geometric Coefficient of Variation 27.00	0.979 Ratio of potassium Geometric Coefficient of Variation 29.36	0.998 Ratio of potassium Geometric Coefficient of Variation 27.81	0.998 Ratio of potassium Geometric Coefficient of Variation 27.78

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Safety analysis set included all participants who received at least one dose of randomised treatment. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in potassium (measured as mmol/L) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=74 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=61 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=72 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=69 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Potassium (mmol/L)	1.004 Ratio of potassium Geometric Coefficient of Variation 27.00	0.979 Ratio of potassium Geometric Coefficient of Variation 29.36	0.998 Ratio of potassium Geometric Coefficient of Variation 27.81	0.998 Ratio of potassium Geometric Coefficient of Variation 27.78

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Safety analysis set included all participants who received at least one dose of randomised treatment. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in calcium (measured as milligram per deciliter (mg/dL)) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=74 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=62 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=72 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=70 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Calcium (mg/dL)	1.017 Ratio of calcium Geometric Coefficient of Variation 20.37	1.018 Ratio of calcium Geometric Coefficient of Variation 20.49	1.008 Ratio of calcium Geometric Coefficient of Variation 20.88	1.010 Ratio of calcium Geometric Coefficient of Variation 22.79

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Safety analysis set included all participants who received at least one dose of randomised treatment. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in calcium (measured as mmol/L) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=74 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=62 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=72 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=70 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Calcium (mmol/L)	1.017 Ratio of calcium Geometric Coefficient of Variation 20.37	1.018 Ratio of calcium Geometric Coefficient of Variation 20.49	1.008 Ratio of calcium Geometric Coefficient of Variation 20.88	1.010 Ratio of calcium Geometric Coefficient of Variation 22.79

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Safety analysis set included all participants who received at least one dose of randomised treatment. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in amylase (measured as units per liter) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=74 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=62 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=72 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=70 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Amylase	1.155 Ratio of amylase Geometric Coefficient of Variation 49.85	1.120 Ratio of amylase Geometric Coefficient of Variation 65.01	1.170 Ratio of amylase Geometric Coefficient of Variation 47.88	1.051 Ratio of amylase Geometric Coefficient of Variation 45.74

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Safety analysis set included all participants who received at least one dose of randomised treatment. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in lipase (measured as units per liter) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=74 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=62 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=72 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=70 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Lipase	1.305 Ratio of lipase Geometric Coefficient of Variation 77.43	1.245 Ratio of lipase Geometric Coefficient of Variation 87.68	1.375 Ratio of lipase Geometric Coefficient of Variation 73.88	1.003 Ratio of lipase Geometric Coefficient of Variation 66.72

SECONDARY outcome

Timeframe: Baseline (week 0), Week 72

Population: Safety analysis set included all participants who received at least one dose of randomised treatment. Overall number of participants analysed = Number of participants who contributed to the analysis.

Change in calcitonin (measured as nanograms per liter) is presented as ratio to baseline. The endpoint was evaluated based on the data from on-treatment period. On-treatment period: the period starting on the date of first administration of trial product and ending on the date of the last dose of trial product +7 days; except for the evaluation of AEs and hypoglycaemic episodes for which the period ended on the date of whatever came first: 1) last dose of trial product + 49 days (7 half-lives of semaglutide); 2) end of the in-trial period.

Outcome measures

Outcome measures
Measure	Semaglutide 0.1 mg n=74 Participants Participants were to receive once daily subcutaneous (s.c.) injection of semaglutide for 72 weeks. Participants initially received 0.05 milligrams (mg) of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.1 mg was reached: 0.05 mg (week 1 to week 4) and 0.1 mg (week 5 to week 72).	Semaglutide 0.2 mg n=62 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.2 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8) and 0.2 mg (week 9 to week 72).	Semaglutide 0.4 mg n=72 Participants Participants were to receive once daily s.c. injection of semaglutide for 72 weeks. Participants initially received 0.05 mg of semaglutide and the dose was then escalated once in 4 weeks until the target dose of 0.4 mg was reached: 0.05 mg (week 1 to week 4), 0.1 mg (week 5 to week 8), 0.2 mg (week 9 to week 12), 0.3 mg (week 13 to week 16) and 0.4 mg (week 17 to week 72).	Placebo n=70 Participants Participants were to receive once daily s.c. injection of placebo matched to semaglutide (0.05 mg, 0.1 mg, 0.2 mg, 0.3 mg or 0.4 mg) for 72 weeks.
Change in Calcitonin	1.040 Ratio of Calcitonin Geometric Coefficient of Variation 62.98	0.937 Ratio of Calcitonin Geometric Coefficient of Variation 65.42	1.000 Ratio of Calcitonin Geometric Coefficient of Variation 66.24	0.950 Ratio of Calcitonin Geometric Coefficient of Variation 62.39

Adverse Events

Semaglutide 0.1 mg

Serious events: 12 serious events

Other events: 61 other events

Deaths: 0 deaths

Semaglutide 0.2 mg

Serious events: 15 serious events

Other events: 64 other events

Deaths: 1 deaths

Semaglutide 0.4 mg

Serious events: 12 serious events

Other events: 63 other events

Deaths: 0 deaths

Placebo

Serious events: 8 serious events

Other events: 55 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Clinical Reporting Anchor and Disclosure (1452)

Novo Nordisk A/S

Phone: (+1) 866-867-7178

Email: [email protected]

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