Trial Outcomes & Findings for Efficacy and Safety of Semaglutide Once-weekly Versus Placebo as add-on to SGLT-2i in Subjects With Type 2 Diabetes Mellitus (NCT NCT03086330)

NCT ID: NCT03086330

Last Updated: 2021-07-02

Results Overview

Change from baseline (week 0) in HbA1c was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose of trial product and ended at the first date of any of the following: 1) the last dose of trial product + 7 days or 2) initiation of rescue medication.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 302 participants
• Primary outcome timeframe: Week 0, week 30
• Results posted on: 2021-07-02

Participant Flow

The trial was conducted at 61 sites in 6 countries as follows: Austria (4 sites), Canada (8 sites), Japan (4 sites), Norway (4 sites), Russian Federation (5 sites), United States of America (USA) (36 sites). In addition, 1 site in Norway and 3 sites in the USA screened, but didn't randomise any participant.

Participant milestones

Measure	Semaglutide 1.0 mg Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as subcutaneous (s.c.) injections.	Placebo Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Overall Study STARTED	151	151
Overall Study Exposed	150	151
Overall Study COMPLETED	147	147
Overall Study NOT COMPLETED	4	4

Reasons for withdrawal

Measure	Semaglutide 1.0 mg Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as subcutaneous (s.c.) injections.	Placebo Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Overall Study Withdrawal by Subject	3	2
Overall Study Lost to Follow-up	1	2

Baseline Characteristics

Efficacy and Safety of Semaglutide Once-weekly Versus Placebo as add-on to SGLT-2i in Subjects With Type 2 Diabetes Mellitus

Baseline characteristics by cohort

Measure	Semaglutide 1.0 mg n=151 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Total n=302 Participants Total of all reporting groups
Age, Continuous	57.5 Years STANDARD_DEVIATION 8.9 • n=5 Participants	56.6 Years STANDARD_DEVIATION 10.1 • n=7 Participants	57.0 Years STANDARD_DEVIATION 9.5 • n=5 Participants
Sex: Female, Male Female	62 Participants n=5 Participants	64 Participants n=7 Participants	126 Participants n=5 Participants
Sex: Female, Male Male	89 Participants n=5 Participants	87 Participants n=7 Participants	176 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	9 Participants n=5 Participants	13 Participants n=7 Participants	22 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	142 Participants n=5 Participants	138 Participants n=7 Participants	280 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska native	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Asian	36 Participants n=5 Participants	35 Participants n=7 Participants	71 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	9 Participants n=5 Participants	4 Participants n=7 Participants	13 Participants n=5 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
Race/Ethnicity, Customized White	100 Participants n=5 Participants	109 Participants n=7 Participants	209 Participants n=5 Participants
Race/Ethnicity, Customized Other	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Glycosylated haemoglobin (HbA1c)	8.0 Percentage HbA1c STANDARD_DEVIATION 0.8 • n=5 Participants	8.1 Percentage HbA1c STANDARD_DEVIATION 0.8 • n=7 Participants	8.0 Percentage HbA1c STANDARD_DEVIATION 0.8 • n=5 Participants

PRIMARY outcome

Timeframe: Week 0, week 30

Population: Full analysis set (FAS), which included all randomised participants. Number analyzed = number of participants with available data.

Change from baseline (week 0) in HbA1c was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose of trial product and ended at the first date of any of the following: 1) the last dose of trial product + 7 days or 2) initiation of rescue medication.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=151 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Change in HbA1c	-0.2 Percentage of HbA1c Standard Deviation 0.9	-1.6 Percentage of HbA1c Standard Deviation 0.8

SECONDARY outcome

Timeframe: Week 0, week 30

Population: FAS which included all randomised participants. Number analyzed = number of participants with available data.

Change from baseline (week 0) in body weight was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=151 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Change in Body Weight (kg)	-1.0 Kg Standard Deviation 3.1	-4.7 Kg Standard Deviation 4.3

SECONDARY outcome

Timeframe: Week 0, week 30

Population: FAS which included all randomised participants. Number analyzed = number of participants with available data.

Change from baseline (week 0) in FPG was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=151 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Change in Fasting Plasma Glucose (FPG)	0.07 mmol/L Standard Deviation 2.07	-2.26 mmol/L Standard Deviation 2.05

SECONDARY outcome

Timeframe: Week 0, week 30

Population: FAS which included all randomised participants. Number analyzed = number of participants with available data.

Change from baseline (week 0) in mean of the SMPG, 7-point profile was evaluated at week 30. Mean 7-point profile (the area under the profile) was calculated using the trapezoidal method and divided by the measurement time. Results are based on the 'on-treatment without rescue medication' observation period. Participants measured their plasma glucose at 7 different time points: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner and at bedtime.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=151 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Change in Self-measured Plasma Glucose (SMPG), 7-point Profile: Mean 7-point Profile	-0.3 mmol/L Standard Deviation 2.0	-2.6 mmol/L Standard Deviation 1.9

SECONDARY outcome

Timeframe: Week 0, week 30

Population: FAS which included all randomised participants. Number analyzed = number of participants with available data.

Change from baseline (week 0) in mean post prandial increment (over all meals) in the SMPG, 7-point profile was evaluated at week 30. The mean increment over all meals was derived as the mean of all available meal increments. Results are based on the 'on-treatment without rescue medication' observation period.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=151 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Change in Self-measured Plasma Glucose (SMPG), 7-point Profile: Mean Post Prandial Increment (Over All Meals)	0.0 mmol/L Standard Deviation 2.2	-1.2 mmol/L Standard Deviation 2.0

SECONDARY outcome

Timeframe: Week 0, week 30

Population: FAS which included all randomised participants. Number analyzed = number of participants with available data.

Change from baseline (week 0) in total cholesterol (measured in mmol/L and presented as ratio to baseline) was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=151 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Change in Fasting Blood Lipid, Total Cholesterol	1.02 Ratio Geometric Coefficient of Variation 18.9	0.91 Ratio Geometric Coefficient of Variation 19.4

SECONDARY outcome

Timeframe: Week 0, week 30

Population: FAS which included all randomised participants. Number analyzed = number of participants with available data.

Change from baseline (week 0) in LDL (measured in mmol/L and presented as ratio to baseline) was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=151 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Change in Fasting Blood Lipid, Low-density Lipoprotein (LDL) Cholesterol	1.04 Ratio Geometric Coefficient of Variation 27.7	0.90 Ratio Geometric Coefficient of Variation 31.6

SECONDARY outcome

Timeframe: Week 0, week 30

Population: FAS which included all randomised participants. Number analyzed = number of participants with available data.

Change from baseline (week 0) in HDL (measured in mmol/L and presented as ratio to baseline) was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=151 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Change in Fasting Blood Lipid, High-density Lipoprotein (HDL) Cholesterol	1.01 Ratio Geometric Coefficient of Variation 13.9	0.99 Ratio Geometric Coefficient of Variation 15.8

SECONDARY outcome

Timeframe: Week 0, week 30

Population: FAS which included all randomised participants. Number analyzed = number of participants with available data.

Change from baseline (week 0) in triglycerides (measured in mmol/L and presented as ratio to baseline) was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=151 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Change in Fasting Blood Lipid, Triglycerides	0.97 Ratio Geometric Coefficient of Variation 38.7	0.81 Ratio Geometric Coefficient of Variation 41.3

SECONDARY outcome

Timeframe: Week 0, week 30

Population: FAS which included all randomised participants. Number analyzed = number of participants with available data.

Percent (%) change from baseline (week 0) in body weight (measured in kilogram (kg)) was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=151 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Change in Body Weight (%)	-1.0 Percentage Standard Deviation 3.1	-5.4 Percentage Standard Deviation 4.8

SECONDARY outcome

Timeframe: Week 0, week 30

Population: FAS which included all randomised participants. Number analyzed = number of participants with available data.

Change from baseline (week 0) in body mass index (BMI) was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period. BMI was calculated as 'body weight in kg/(height in meters) x (height in meters)'.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=151 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Change in Body Mass Index	-0.4 Kg/sqm Standard Deviation 1.1	-1.7 Kg/sqm Standard Deviation 1.5

SECONDARY outcome

Timeframe: Week 0, week 30

Population: FAS which included all randomised participants. Number analyzed = number of participants with available data.

Change from baseline (week 0) in waist circumference was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=151 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Change in Waist Circumference	-1.8 cm Standard Deviation 4.5	-4.4 cm Standard Deviation 5.5

SECONDARY outcome

Timeframe: Week 0, week 30

Population: FAS which included all randomised participants. Number analyzed = number of participants with available data.

Change from baseline (week 0) in systolic blood pressure was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=151 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Change in Systolic Blood Pressure	1.1 mmHg Standard Deviation 12.3	-4.3 mmHg Standard Deviation 14.5

SECONDARY outcome

Timeframe: Week 0, week 30

Population: FAS which included all randomised participants. Number analyzed = number of participants with available data.

Change from baseline (week 0) in diastolic blood pressure was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=151 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Change in Diastolic Blood Pressure	-0.1 mmHg Standard Deviation 6.7	-0.1 mmHg Standard Deviation 8.1

SECONDARY outcome

Timeframe: Week 0, week 30

Population: FAS which included all randomised participants. Number analyzed = number of participants with available data. Results are based on the 'on-treatment without rescue medication' observation period.

Change from baseline (week 0) in patient reported outcome (PRO) questionnaire, SF-36v2TM was evaluated at week 30. The SF-36v2™ questionnaire was used to assess the overall health related quality of life of participants. This questionnaire contains 36 items and measures the individual overall health related quality of life on 8 domains: 1) Physical functioning, 2) Role functioning, 3) Bodily pain, 4) General health, 5) Vitality, 6) Social functioning, 7) Role emotional and 8) Mental health. Each item is scored on a scale from 1 to either 2, 3, 5, or 6; each item score is then converted to a scale of 0-100, representing the percentage of total possible score achieved and with higher scores indicating a higher health status; items on the same scale are then averaged to obtain the 8 scale scores. Physical component summary (PCS) includes domains 1-4 and mental component summary (MCS) includes domains 5-8. Higher PCS and MCS scores on a scale of 0-100 indicate a higher health status.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=151 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Change in Scores for Selected Patient Reported Outcomes: Short-form Health Survey (SF-36v2TM): Total Scores (Physical Component and Mental Component) and Scores From the 8 Domains Physical component summary	0.7 Scores on a scale Standard Deviation 5.4	1.9 Scores on a scale Standard Deviation 4.9
Change in Scores for Selected Patient Reported Outcomes: Short-form Health Survey (SF-36v2TM): Total Scores (Physical Component and Mental Component) and Scores From the 8 Domains 1) Physical functioning	1.1 Scores on a scale Standard Deviation 5.2	1.3 Scores on a scale Standard Deviation 4.1
Change in Scores for Selected Patient Reported Outcomes: Short-form Health Survey (SF-36v2TM): Total Scores (Physical Component and Mental Component) and Scores From the 8 Domains 2) Role functioning	0.0 Scores on a scale Standard Deviation 6.0	1.5 Scores on a scale Standard Deviation 6.1
Change in Scores for Selected Patient Reported Outcomes: Short-form Health Survey (SF-36v2TM): Total Scores (Physical Component and Mental Component) and Scores From the 8 Domains 3) Bodily pain	0.1 Scores on a scale Standard Deviation 8.1	0.9 Scores on a scale Standard Deviation 7.4
Change in Scores for Selected Patient Reported Outcomes: Short-form Health Survey (SF-36v2TM): Total Scores (Physical Component and Mental Component) and Scores From the 8 Domains 4) General health	0.1 Scores on a scale Standard Deviation 6.8	2.7 Scores on a scale Standard Deviation 6.8
Change in Scores for Selected Patient Reported Outcomes: Short-form Health Survey (SF-36v2TM): Total Scores (Physical Component and Mental Component) and Scores From the 8 Domains Mental component summary	-0.9 Scores on a scale Standard Deviation 6.3	0.1 Scores on a scale Standard Deviation 5.6
Change in Scores for Selected Patient Reported Outcomes: Short-form Health Survey (SF-36v2TM): Total Scores (Physical Component and Mental Component) and Scores From the 8 Domains 5) Vitality	0.2 Scores on a scale Standard Deviation 6.7	1.5 Scores on a scale Standard Deviation 6.2
Change in Scores for Selected Patient Reported Outcomes: Short-form Health Survey (SF-36v2TM): Total Scores (Physical Component and Mental Component) and Scores From the 8 Domains 6) Social functioning	-1.0 Scores on a scale Standard Deviation 7.4	0.3 Scores on a scale Standard Deviation 7.3
Change in Scores for Selected Patient Reported Outcomes: Short-form Health Survey (SF-36v2TM): Total Scores (Physical Component and Mental Component) and Scores From the 8 Domains 7) Role emotional	-0.2 Scores on a scale Standard Deviation 7.5	0.1 Scores on a scale Standard Deviation 6.7
Change in Scores for Selected Patient Reported Outcomes: Short-form Health Survey (SF-36v2TM): Total Scores (Physical Component and Mental Component) and Scores From the 8 Domains 8) Mental health	-0.6 Scores on a scale Standard Deviation 6.0	0.5 Scores on a scale Standard Deviation 5.2

SECONDARY outcome

Timeframe: Week 0, week 30

Population: FAS which included all randomised participants. Number analyzed = number of participants with available data.

Change from baseline (week 0) in PRO questionnaire, DTSQ was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period. The DTSQ measures satisfaction with diabetes treatment. The DTSQ consists of 8 items evaluating 6 aspects of treatment satisfaction and 2 perceived recent event rates of hyperglycemia/hypoglycemia. Each item is scored on a 7- point Likert scale ranging from 0 (very dissatisfied) to 6 (very satisfied). Items evaluating 6 aspects (items 3-8) of treatment satisfaction are summed to produce a total treatment satisfaction score; DTSQ status total scores range from 0-36, with higher scores indicating greater satisfaction; the perceived frequency of hyperglycemia/hypoglycemia items are scored separately, with lower scores indicating better perceived blood glucose control.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=151 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Change in Scores for Selected Patient Reported Outcomes: Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment Satisfaction Score (Sum of 6 of 8 Items) and the 8 Items Separately 1) Feeling of unacceptably high blood sugars	-0.8 Scores on a scale Standard Deviation 2.2	-2.2 Scores on a scale Standard Deviation 1.9
Change in Scores for Selected Patient Reported Outcomes: Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment Satisfaction Score (Sum of 6 of 8 Items) and the 8 Items Separately 2) Feeling of unacceptably low blood sugars	-0.4 Scores on a scale Standard Deviation 1.5	0.3 Scores on a scale Standard Deviation 1.5
Change in Scores for Selected Patient Reported Outcomes: Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment Satisfaction Score (Sum of 6 of 8 Items) and the 8 Items Separately Total treatment satisfaction score (Sum of 3-8)	1.9 Scores on a scale Standard Deviation 7.0	4.2 Scores on a scale Standard Deviation 6.6
Change in Scores for Selected Patient Reported Outcomes: Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment Satisfaction Score (Sum of 6 of 8 Items) and the 8 Items Separately 3) Satisfaction with current treatment	0.2 Scores on a scale Standard Deviation 1.4	0.8 Scores on a scale Standard Deviation 1.6
Change in Scores for Selected Patient Reported Outcomes: Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment Satisfaction Score (Sum of 6 of 8 Items) and the 8 Items Separately 4) Convenience of current treatment	0.5 Scores on a scale Standard Deviation 1.3	0.7 Scores on a scale Standard Deviation 1.3
Change in Scores for Selected Patient Reported Outcomes: Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment Satisfaction Score (Sum of 6 of 8 Items) and the 8 Items Separately 5) Flexibility of current treatment	0.4 Scores on a scale Standard Deviation 1.7	0.7 Scores on a scale Standard Deviation 1.5
Change in Scores for Selected Patient Reported Outcomes: Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment Satisfaction Score (Sum of 6 of 8 Items) and the 8 Items Separately 6) Satisfaction with understanding of diabetes	0.5 Scores on a scale Standard Deviation 1.5	0.5 Scores on a scale Standard Deviation 1.2
Change in Scores for Selected Patient Reported Outcomes: Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment Satisfaction Score (Sum of 6 of 8 Items) and the 8 Items Separately 7) Recommending treatment to others	0.2 Scores on a scale Standard Deviation 1.8	0.8 Scores on a scale Standard Deviation 1.3
Change in Scores for Selected Patient Reported Outcomes: Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment Satisfaction Score (Sum of 6 of 8 Items) and the 8 Items Separately 8) Satisfaction to continue with present treatment	0.2 Scores on a scale Standard Deviation 1.7	0.8 Scores on a scale Standard Deviation 1.7

SECONDARY outcome

Timeframe: After 30 weeks

Population: FAS which included all randomised participants. Number analyzed = number of participants with available data.

Percentage of participants with HbA1c below 7.0% (53 mmol/mol) was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.

Outcome measures

Measure	Placebo n=127 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=120 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
HbA1c Below 7.0% (53 mmol/Mol)	20.5 Percentage of participants	82.5 Percentage of participants

SECONDARY outcome

Timeframe: After 30 weeks

Population: FAS which included all randomised participants. Number analyzed = number of participants with available data.

Percentage of participants with HbA1c equal to or below 6.5% (48 mmol/mol) was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.

Outcome measures

Measure	Placebo n=127 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=120 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
HbA1c Equal to or Below 6.5% (48 mmol/Mol)	3.9 Percentage of participants	60.0 Percentage of participants

SECONDARY outcome

Timeframe: After 30 weeks

Population: FAS which included all randomised participants. Number analyzed = number of participants with available data.

Percentage of participants with weight loss equal to or above 3% of their baseline (week 0) body weight was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.

Outcome measures

Measure	Placebo n=128 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=121 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Weight Loss Equal to or Above 3%	21.1 Percentage of participants	69.4 Percentage of participants

SECONDARY outcome

Timeframe: After 30 weeks

Population: FAS which included all randomised participants. Number analyzed = number of participants with available data.

Percentage of participants with weight loss equal to or above 5% of their baseline (week 0) body weight was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.

Outcome measures

Measure	Placebo n=128 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=121 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Weight Loss Equal to or Above 5%	7.8 Percentage of participants	50.4 Percentage of participants

SECONDARY outcome

Timeframe: After 30 weeks

Population: FAS which included all randomised participants. Number analyzed = number of participants with available data.

Percentage of participants with weight loss equal to or above 10% of their baseline (week 0) body weight was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.

Outcome measures

Measure	Placebo n=128 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=121 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Weight Loss Equal to or Above 10%	1.6 Percentage of participants	15.7 Percentage of participants

SECONDARY outcome

Timeframe: After 30 weeks

Population: FAS which included all randomised participants. Number analyzed = number of participants with available data.

Percentage of participants with HbA1c below 7.0% (53 mmol/mol) without severe or BG confirmed symptomatic hypoglycaemia episodes and no weight gain from their baseline (week 0) body weight was evaluated at week 30. Severe or blood glucose (BG)-confirmed symptomatic hypoglycaemia: an episode that was severe according to the American Diabetes Association (ADA) classification or confirmed by a plasma glucose (PG) value below 3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. Results are based on the 'on-treatment without rescue medication' observation period.

Outcome measures

Measure	Placebo n=127 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=120 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
HbA1c Below 7.0% (53 mmol/Mol) Without Severe or BG Confirmed Symptomatic Hypoglycaemia Episodes and no Weight Gain	17.3 Percentage of participants	72.5 Percentage of participants

SECONDARY outcome

Timeframe: After 30 weeks

Population: FAS which included all randomised participants. Number analyzed = number of participants with available data.

Percentage of participants with HbA1c reduction equal to or above 1%-point was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.

Outcome measures

Measure	Placebo n=127 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=120 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
HbA1c Reduction Equal to or Above 1%-Point	15.0 Percentage of participants	80.8 Percentage of participants

SECONDARY outcome

Timeframe: After 30 weeks

Population: FAS which included all randomised participants. Number analyzed = number of participants with available data.

Percentage of participants with HbA1c reduction equal to or above 1%-point and weight loss equal to or above 3% of their baseline (week 0) body weight was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.

Outcome measures

Measure	Placebo n=127 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=120 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
HbA1c Reduction Equal to or Above 1%-Point and Weight Loss Equal to or Above 3%	7.9 Percentage of participants	56.7 Percentage of participants

SECONDARY outcome

Timeframe: After 30 weeks

Population: FAS which included all randomised participants. Number analyzed = number of participants with available data.

Percentage of participants with HbA1c reduction equal to or above 1%-point and weight loss equal to or above 5% of their baseline (week 0) body weight was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.

Outcome measures

Measure	Placebo n=127 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=120 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
HbA1c Reduction Equal to or Above 1%-Point and Weight Loss Equal to or Above 5%	4.7 Percentage of participants	41.7 Percentage of participants

SECONDARY outcome

Timeframe: After 30 weeks

Population: FAS which included all randomised participants. Number analyzed = number of participants with available data.

Percentage of participants with HbA1c reduction equal to or above 1%-point and weight loss equal to or above 10% of their baseline (week 0) body weight was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.

Outcome measures

Measure	Placebo n=127 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=120 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
HbA1c Reduction Equal to or Above 1%-Point and Weight Loss Equal to or Above 10%	1.6 Percentage of participants	15.0 Percentage of participants

SECONDARY outcome

Timeframe: Week 0 - week 30

Population: Safety analysis set (SAS), which included all participants exposed to at least one dose of trial product (semaglutide or placebo).

A TEAE was defined as an event that has onset date (or increase in severity) during the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 42 days.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=150 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Number of Treatment-emergent Adverse Events (TEAEs)	247 Events	356 Events

SECONDARY outcome

Timeframe: Week 0 - week 30

Population: SAS, which included all participants exposed to at least one dose of trial product.

Hypoglycaemic episodes were defined as treatment emergent if the onset of the episode occurred within the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 42 days. Severe or BG-confirmed symptomatic hypoglycaemia: an episode that was severe according to the ADA classification or confirmed by a PG value below 3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=150 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Number of Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes	0 Episodes	4 Episodes

SECONDARY outcome

Timeframe: Week 0, week 30

Population: SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Change from baseline (week 0) in haemoglobin was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=150 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Change in Haematology: Haemoglobin	1.1 mmol/L Geometric Coefficient of Variation 29.3	1.1 mmol/L Geometric Coefficient of Variation 22.1

SECONDARY outcome

Timeframe: Week 0, week 30

Population: SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Change from baseline (week 0) in haematocrit was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=150 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Change in Haematology: Haematocrit	1.1 % of red blood cells Geometric Coefficient of Variation 155.1	1.4 % of red blood cells Geometric Coefficient of Variation 130.3

SECONDARY outcome

Timeframe: Week 0, week 30

Population: SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Change from baseline (week 0) in thrombocytes was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=150 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Change in Haematology: Thrombocytes	20.2 10^9 thrombocytes/L Geometric Coefficient of Variation 100.7	25.3 10^9 thrombocytes/L Geometric Coefficient of Variation 94.9

SECONDARY outcome

Timeframe: Week 0, week 30

Population: SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Change from baseline (week 0) in erythrocytes was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=150 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Change in Haematology: Erythrocytes	0.11 10^12 erythrocytes/L Geometric Coefficient of Variation 168.3	0.16 10^12 erythrocytes/L Geometric Coefficient of Variation 111.0

SECONDARY outcome

Timeframe: Week 0, week 30

Population: SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Change from baseline (week 0) in leucocytes was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=150 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Change in Haematology: Leucocytes	0.54 10^9 leucocytes/L Geometric Coefficient of Variation 146.8	0.65 10^9 leucocytes/L Geometric Coefficient of Variation 186.6

SECONDARY outcome

Timeframe: Week 0, week 30

Population: SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Change from baseline (week 0) in amylase was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=150 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Change in Biochemistry: Amylase	5.0 U/L Geometric Coefficient of Variation 121.7	10.2 U/L Geometric Coefficient of Variation 113.8

SECONDARY outcome

Timeframe: Week 0, week 30

Population: SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Change from baseline (week 0) in lipase was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=150 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Change in Biochemistry: Lipase	4.5 U/L Geometric Coefficient of Variation 171.8	11.6 U/L Geometric Coefficient of Variation 140.2

SECONDARY outcome

Timeframe: Week 0, week 30

Population: SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Change from baseline (week 0) in alkaline phosphatase was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=150 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Change in Biochemistry: Alkaline Phosphatase	7.2 U/L Geometric Coefficient of Variation 106.7	4.6 U/L Geometric Coefficient of Variation 171.2

SECONDARY outcome

Timeframe: Week 0, week 30

Population: SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Change from baseline (week 0) in alanine aminotransferase was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=150 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Change in Biochemistry: Alanine Aminotransferase	4.8 U/L Geometric Coefficient of Variation 166.7	4.5 U/L Geometric Coefficient of Variation 123.2

SECONDARY outcome

Timeframe: Week 0, week 30

Population: SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Change from baseline (week 0) in aspartate aminotransferase was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=150 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Change in Biochemistry: Aspartate Aminotransferase	3.5 U/L Geometric Coefficient of Variation 90.1	3.4 U/L Geometric Coefficient of Variation 112.3

SECONDARY outcome

Timeframe: Week 0, week 30

Population: SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Change from baseline (week 0) in total bilirubin was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=150 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Change in Biochemistry: Total Bilirubin	1.7 umol/L Geometric Coefficient of Variation 134.8	2.3 umol/L Geometric Coefficient of Variation 128.1

SECONDARY outcome

Timeframe: Week 0, week 30

Population: SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Change from baseline (week 0) in albumin was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=150 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Change in Biochemistry: Albumin	0.1 g/dL Geometric Coefficient of Variation 48.6	0.1 g/dL Geometric Coefficient of Variation 45.4

SECONDARY outcome

Timeframe: Week 0, week 30

Population: SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Change from baseline (week 0) in albumin was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=150 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Change in Biochemistry: Calcium (Total)	0.05 mmol/L Geometric Coefficient of Variation 88.9	0.04 mmol/L Geometric Coefficient of Variation 125.0

SECONDARY outcome

Timeframe: Week 0, week 30

Population: SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Change from baseline (week 0) in potassium was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=150 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Change in Biochemistry: Potassium	0.2 mmol/L Geometric Coefficient of Variation 73.7	0.3 mmol/L Geometric Coefficient of Variation 89.5

SECONDARY outcome

Timeframe: Week 0, week 30

Population: SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Change from baseline (week 0) in sodium was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=150 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Change in Biochemistry: Sodium	1.5 mmol/L Geometric Coefficient of Variation 48.4	1.7 mmol/L Geometric Coefficient of Variation 55.8

SECONDARY outcome

Timeframe: Week 0, week 30

Population: SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Change from baseline (week 0) in bicarbonate was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=150 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Change in Biochemistry: Bicarbonate	2.1 mmol/L Geometric Coefficient of Variation 69.0	2.2 mmol/L Geometric Coefficient of Variation 67.6

SECONDARY outcome

Timeframe: Week 0, week 30

Population: SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Change from baseline (week 0) in eGFR was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=150 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Change in Biochemistry: Estimated Glomerular Filtration Rate (eGFR)	3.2 mL/min/1.73m2 Geometric Coefficient of Variation 105.6	3.4 mL/min/1.73m2 Geometric Coefficient of Variation 114.8

SECONDARY outcome

Timeframe: Week 0, week 30

Population: SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Change from baseline (week 0) in creatinine was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=150 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Change in Biochemistry: Creatinine	2.6 umol/L Geometric Coefficient of Variation 191.5	4.6 umol/L Geometric Coefficient of Variation 118.8

SECONDARY outcome

Timeframe: Week 0, week 30

Population: SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Change from baseline (week 0) in calcitonin was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=150 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Change in Calcitonin	1.7 ng/L Geometric Coefficient of Variation 171.1	1.3 ng/L Geometric Coefficient of Variation 172.1

SECONDARY outcome

Timeframe: Week 0, week 30

Population: SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Change from baseline (week 0) in pulse rate was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=150 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Change in Pulse	0.1 beats/min Standard Deviation 8.4	4.0 beats/min Standard Deviation 9.6

SECONDARY outcome

Timeframe: Week 0, week 30

Population: SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Electrocardiogram (ECG) results are presented for week 0 (baseline) and week 30. ECG finding are presented as percentage of participants with normal, abnormal non-clinically significant (NCS) and abnormal clinically significant (CS) ECG values. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 42 days.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=150 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Change in Electrocardiogram Week 0: Abnormal, CS	1.3 Percentage of participants	0.7 Percentage of participants
Change in Electrocardiogram Week 0: Normal	66.2 Percentage of participants	62.4 Percentage of participants
Change in Electrocardiogram Week 0: Abnormal, NCS	32.5 Percentage of participants	36.9 Percentage of participants
Change in Electrocardiogram Week 30: Normal	66.4 Percentage of participants	64.3 Percentage of participants
Change in Electrocardiogram Week 30: Abnormal, NCS	32.2 Percentage of participants	34.9 Percentage of participants
Change in Electrocardiogram Week 30: Abnormal, CS	1.4 Percentage of participants	0.8 Percentage of participants

SECONDARY outcome

Timeframe: Week -2, week 30

Population: SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Physical examination (general appearance) results are presented for week -2 (baseline) and week 30. Results are presented as percentage of participants with normal, abnormal NCS and abnormal CS findings. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=150 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Change in Physical Examination: General Appearance Week -2: Normal	86.0 Percentage of participants	90.0 Percentage of participants
Change in Physical Examination: General Appearance Week -2: Abnormal, NCS	14.0 Percentage of participants	10.0 Percentage of participants
Change in Physical Examination: General Appearance Week -2: Abnormal, CS	0 Percentage of participants	0 Percentage of participants
Change in Physical Examination: General Appearance Week 30: Normal	87.1 Percentage of participants	87.6 Percentage of participants
Change in Physical Examination: General Appearance Week 30: Abnormal, NCS	12.2 Percentage of participants	11.6 Percentage of participants
Change in Physical Examination: General Appearance Week 30: Abnormal, CS	0.7 Percentage of participants	0.8 Percentage of participants

SECONDARY outcome

Timeframe: Week -2, week 30

Population: SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Physical examination (central and peripheral nervous system) results are presented for week -2 (baseline) and week 30. Results are presented as percentage of participants with normal, abnormal NCS and abnormal CS findings. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=150 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Change in Physical Examination: Central and Peripheral Nervous System Week -2: Abnormal, CS	0.7 Percentage of participants	0.7 Percentage of participants
Change in Physical Examination: Central and Peripheral Nervous System Week -2: Normal	86.7 Percentage of participants	92.0 Percentage of participants
Change in Physical Examination: Central and Peripheral Nervous System Week -2: Abnormal, NCS	12.7 Percentage of participants	7.3 Percentage of participants
Change in Physical Examination: Central and Peripheral Nervous System Week 30: Normal	87.8 Percentage of participants	94.2 Percentage of participants
Change in Physical Examination: Central and Peripheral Nervous System Week 30: Abnormal, NCS	12.2 Percentage of participants	5.0 Percentage of participants
Change in Physical Examination: Central and Peripheral Nervous System Week 30: Abnormal, CS	0 Percentage of participants	0.8 Percentage of participants

SECONDARY outcome

Timeframe: Week -2, week 30

Population: SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Physical examination (cardiovascular system) results are presented for week -2 (baseline) and week 30. Results are presented as percentage of participants with normal, abnormal NCS and abnormal CS findings. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=150 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Change in Physical Examination: Cardiovascular System Week 30: Abnormal, CS	0 Percentage of participants	0 Percentage of participants
Change in Physical Examination: Cardiovascular System Week -2: Normal	93.3 Percentage of participants	98.7 Percentage of participants
Change in Physical Examination: Cardiovascular System Week -2: Abnormal, NCS	6.0 Percentage of participants	1.3 Percentage of participants
Change in Physical Examination: Cardiovascular System Week -2: Abnormal, CS	0.7 Percentage of participants	0 Percentage of participants
Change in Physical Examination: Cardiovascular System Week 30: Normal	92.8 Percentage of participants	98.3 Percentage of participants
Change in Physical Examination: Cardiovascular System Week 30: Abnormal, NCS	7.2 Percentage of participants	1.7 Percentage of participants

SECONDARY outcome

Timeframe: Week -2, week 30

Population: SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Physical examination (gastrointestinal system including mouth) results are presented for week -2 (baseline) and week 30. Results are presented as percentage of participants with normal, abnormal NCS and abnormal CS findings. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=150 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Change in Physical Examination: Gastrointestinal System Including Mouth Week -2: Normal	93.3 Percentage of participants	93.3 Percentage of participants
Change in Physical Examination: Gastrointestinal System Including Mouth Week -2: Abnormal, NCS	6.7 Percentage of participants	6.7 Percentage of participants
Change in Physical Examination: Gastrointestinal System Including Mouth Week -2: Abnormal, CS	0 Percentage of participants	0 Percentage of participants
Change in Physical Examination: Gastrointestinal System Including Mouth Week 30: Normal	94.2 Percentage of participants	95.9 Percentage of participants
Change in Physical Examination: Gastrointestinal System Including Mouth Week 30: Abnormal, NCS	5.8 Percentage of participants	3.3 Percentage of participants
Change in Physical Examination: Gastrointestinal System Including Mouth Week 30: Abnormal, CS	0 Percentage of participants	0.8 Percentage of participants

SECONDARY outcome

Timeframe: Week -2, week 30

Population: SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Physical examination (skin) results are presented for week -2 (baseline) and week 30. Results are presented as percentage of participants with normal, abnormal NCS and abnormal CS findings. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=150 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Change in Physical Examination: Skin Week -2: Abnormal, CS	0 Percentage of participants	0 Percentage of participants
Change in Physical Examination: Skin Week -2: Normal	93.3 Percentage of participants	91.3 Percentage of participants
Change in Physical Examination: Skin Week -2: Abnormal, NCS	6.7 Percentage of participants	8.7 Percentage of participants
Change in Physical Examination: Skin Week 30: Normal	95.0 Percentage of participants	93.4 Percentage of participants
Change in Physical Examination: Skin Week 30: Abnormal, NCS	4.3 Percentage of participants	6.6 Percentage of participants
Change in Physical Examination: Skin Week 30: Abnormal, CS	0.7 Percentage of participants	0 Percentage of participants

SECONDARY outcome

Timeframe: Week -2, week 30

Population: SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Physical examination (respiratory system) results are presented for week -2 (baseline) and week 30. Results are presented as percentage of participants with normal, abnormal NCS and abnormal CS findings. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=150 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Change in Physical Examination: Respiratory System Week -2: Normal	98.7 Percentage of participants	100 Percentage of participants
Change in Physical Examination: Respiratory System Week -2: Abnormal, NCS	1.3 Percentage of participants	0 Percentage of participants
Change in Physical Examination: Respiratory System Week -2: Abnormal, CS	0 Percentage of participants	0 Percentage of participants
Change in Physical Examination: Respiratory System Week 30: Normal	99.3 Percentage of participants	100 Percentage of participants
Change in Physical Examination: Respiratory System Week 30: Abnormal, NCS	0.7 Percentage of participants	0 Percentage of participants
Change in Physical Examination: Respiratory System Week 30: Abnormal, CS	0 Percentage of participants	0 Percentage of participants

SECONDARY outcome

Timeframe: Week -2, week 30

Population: SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Physical examination (lymph node palpation) results are presented for week -2 (baseline) and week 30. Results are presented as percentage of participants with normal, abnormal NCS and abnormal CS findings. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=150 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Change in Physical Examination: Lymph Node Palpation Week -2: Normal	100 Percentage of participants	99.3 Percentage of participants
Change in Physical Examination: Lymph Node Palpation Week -2: Abnormal, NCS	0 Percentage of participants	0.7 Percentage of participants
Change in Physical Examination: Lymph Node Palpation Week -2: Abnormal, CS	0 Percentage of participants	0 Percentage of participants
Change in Physical Examination: Lymph Node Palpation Week 30: Normal	100 Percentage of participants	99.2 Percentage of participants
Change in Physical Examination: Lymph Node Palpation Week 30: Abnormal, NCS	0 Percentage of participants	0 Percentage of participants
Change in Physical Examination: Lymph Node Palpation Week 30: Abnormal, CS	0 Percentage of participants	0.8 Percentage of participants

SECONDARY outcome

Timeframe: Week -2, week 30

Population: SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Physical examination (thyroid gland) results are presented for week -2 (baseline) and week 30. Results are presented as percentage of participants with normal, abnormal NCS and abnormal CS findings. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=150 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Change in Physical Examination: Thyroid Gland Week -2: Normal	96.7 Percentage of participants	98.0 Percentage of participants
Change in Physical Examination: Thyroid Gland Week -2: Abnormal, NCS	3.3 Percentage of participants	2.0 Percentage of participants
Change in Physical Examination: Thyroid Gland Week -2: Abnormal, CS	0 Percentage of participants	0 Percentage of participants
Change in Physical Examination: Thyroid Gland Week 30: Normal	97.1 Percentage of participants	99.2 Percentage of participants
Change in Physical Examination: Thyroid Gland Week 30: Abnormal, NCS	2.9 Percentage of participants	0.8 Percentage of participants
Change in Physical Examination: Thyroid Gland Week 30: Abnormal, CS	0 Percentage of participants	0 Percentage of participants

SECONDARY outcome

Timeframe: Week 0, week 30

Population: SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Fundoscopy results for both left and right eyes are presented for week 0 (baseline) and week 30. Results are presented as percentage of participants with normal, abnormal NCS and abnormal CS findings. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.

Outcome measures

Measure	Placebo n=151 Participants Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Semaglutide 1.0 mg n=150 Participants Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.
Change in Fundoscopy Left eye: Week 0; normal	62.0 Percentage of participants	70.7 Percentage of participants
Change in Fundoscopy Left eye: Week 0; abnormal, NCS	32.7 Percentage of participants	24.7 Percentage of participants
Change in Fundoscopy Left eye: Week 0; abnormal, CS	5.3 Percentage of participants	4.7 Percentage of participants
Change in Fundoscopy Left eye: Week 30; normal	64.1 Percentage of participants	79.3 Percentage of participants
Change in Fundoscopy Left eye: Week 30; abnormal, NCS	31.5 Percentage of participants	17.1 Percentage of participants
Change in Fundoscopy Left eye: Week 30; abnormal, CS	4.3 Percentage of participants	3.7 Percentage of participants
Change in Fundoscopy Right eye: Week 0; normal	62.4 Percentage of participants	69.3 Percentage of participants
Change in Fundoscopy Right eye: Week 0; abnormal, NCS	30.9 Percentage of participants	25.3 Percentage of participants
Change in Fundoscopy Right eye: Week 0; abnormal, CS	6.7 Percentage of participants	5.3 Percentage of participants
Change in Fundoscopy Right eye: Week 30; normal	63.7 Percentage of participants	75.6 Percentage of participants
Change in Fundoscopy Right eye: Week 30; abnormal, NCS	31.9 Percentage of participants	19.5 Percentage of participants
Change in Fundoscopy Right eye: Week 30; abnormal, CS	4.4 Percentage of participants	4.9 Percentage of participants

Adverse Events

Semaglutide 1.0 mg

Serious events: 7 serious events

Other events: 49 other events

Deaths: 0 deaths

Placebo

Serious events: 6 serious events

Other events: 28 other events

Deaths: 0 deaths

Serious adverse events

Measure	Semaglutide 1.0 mg n=150 participants at risk Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Placebo n=151 participants at risk Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Injury, poisoning and procedural complications Accidental overdose	0.67% 1/150 • Number of events 1 • Week 0 to week 30 (treatment period) + 42 days (follow-up period). All the reported adverse events (AEs) are TEAEs. Results are based on the SAS. Treatment with semaglutide or placebo followed a fixed dose escalation. The maintenance dose of semaglutide 1.0 mg was reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg. The same fixed dose escalation scheme was followed for placebo, with respective dose matching volume. Hence, the adverse events are combinedly presented under 2 respective reporting groups, 'semaglutide 1.0 mg and placebo'.	0.00% 0/151 • Week 0 to week 30 (treatment period) + 42 days (follow-up period). All the reported adverse events (AEs) are TEAEs. Results are based on the SAS. Treatment with semaglutide or placebo followed a fixed dose escalation. The maintenance dose of semaglutide 1.0 mg was reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg. The same fixed dose escalation scheme was followed for placebo, with respective dose matching volume. Hence, the adverse events are combinedly presented under 2 respective reporting groups, 'semaglutide 1.0 mg and placebo'.
Renal and urinary disorders Acute kidney injury	0.67% 1/150 • Number of events 1 • Week 0 to week 30 (treatment period) + 42 days (follow-up period). All the reported adverse events (AEs) are TEAEs. Results are based on the SAS. Treatment with semaglutide or placebo followed a fixed dose escalation. The maintenance dose of semaglutide 1.0 mg was reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg. The same fixed dose escalation scheme was followed for placebo, with respective dose matching volume. Hence, the adverse events are combinedly presented under 2 respective reporting groups, 'semaglutide 1.0 mg and placebo'.	0.00% 0/151 • Week 0 to week 30 (treatment period) + 42 days (follow-up period). All the reported adverse events (AEs) are TEAEs. Results are based on the SAS. Treatment with semaglutide or placebo followed a fixed dose escalation. The maintenance dose of semaglutide 1.0 mg was reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg. The same fixed dose escalation scheme was followed for placebo, with respective dose matching volume. Hence, the adverse events are combinedly presented under 2 respective reporting groups, 'semaglutide 1.0 mg and placebo'.
Cardiac disorders Angina unstable	0.67% 1/150 • Number of events 1 • Week 0 to week 30 (treatment period) + 42 days (follow-up period). All the reported adverse events (AEs) are TEAEs. Results are based on the SAS. Treatment with semaglutide or placebo followed a fixed dose escalation. The maintenance dose of semaglutide 1.0 mg was reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg. The same fixed dose escalation scheme was followed for placebo, with respective dose matching volume. Hence, the adverse events are combinedly presented under 2 respective reporting groups, 'semaglutide 1.0 mg and placebo'.	0.00% 0/151 • Week 0 to week 30 (treatment period) + 42 days (follow-up period). All the reported adverse events (AEs) are TEAEs. Results are based on the SAS. Treatment with semaglutide or placebo followed a fixed dose escalation. The maintenance dose of semaglutide 1.0 mg was reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg. The same fixed dose escalation scheme was followed for placebo, with respective dose matching volume. Hence, the adverse events are combinedly presented under 2 respective reporting groups, 'semaglutide 1.0 mg and placebo'.
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/150 • Week 0 to week 30 (treatment period) + 42 days (follow-up period). All the reported adverse events (AEs) are TEAEs. Results are based on the SAS. Treatment with semaglutide or placebo followed a fixed dose escalation. The maintenance dose of semaglutide 1.0 mg was reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg. The same fixed dose escalation scheme was followed for placebo, with respective dose matching volume. Hence, the adverse events are combinedly presented under 2 respective reporting groups, 'semaglutide 1.0 mg and placebo'.	0.66% 1/151 • Number of events 1 • Week 0 to week 30 (treatment period) + 42 days (follow-up period). All the reported adverse events (AEs) are TEAEs. Results are based on the SAS. Treatment with semaglutide or placebo followed a fixed dose escalation. The maintenance dose of semaglutide 1.0 mg was reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg. The same fixed dose escalation scheme was followed for placebo, with respective dose matching volume. Hence, the adverse events are combinedly presented under 2 respective reporting groups, 'semaglutide 1.0 mg and placebo'.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.67% 1/150 • Number of events 3 • Week 0 to week 30 (treatment period) + 42 days (follow-up period). All the reported adverse events (AEs) are TEAEs. Results are based on the SAS. Treatment with semaglutide or placebo followed a fixed dose escalation. The maintenance dose of semaglutide 1.0 mg was reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg. The same fixed dose escalation scheme was followed for placebo, with respective dose matching volume. Hence, the adverse events are combinedly presented under 2 respective reporting groups, 'semaglutide 1.0 mg and placebo'.	0.00% 0/151 • Week 0 to week 30 (treatment period) + 42 days (follow-up period). All the reported adverse events (AEs) are TEAEs. Results are based on the SAS. Treatment with semaglutide or placebo followed a fixed dose escalation. The maintenance dose of semaglutide 1.0 mg was reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg. The same fixed dose escalation scheme was followed for placebo, with respective dose matching volume. Hence, the adverse events are combinedly presented under 2 respective reporting groups, 'semaglutide 1.0 mg and placebo'.
Gastrointestinal disorders Colitis ischaemic	0.67% 1/150 • Number of events 1 • Week 0 to week 30 (treatment period) + 42 days (follow-up period). All the reported adverse events (AEs) are TEAEs. Results are based on the SAS. Treatment with semaglutide or placebo followed a fixed dose escalation. The maintenance dose of semaglutide 1.0 mg was reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg. The same fixed dose escalation scheme was followed for placebo, with respective dose matching volume. Hence, the adverse events are combinedly presented under 2 respective reporting groups, 'semaglutide 1.0 mg and placebo'.	0.00% 0/151 • Week 0 to week 30 (treatment period) + 42 days (follow-up period). All the reported adverse events (AEs) are TEAEs. Results are based on the SAS. Treatment with semaglutide or placebo followed a fixed dose escalation. The maintenance dose of semaglutide 1.0 mg was reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg. The same fixed dose escalation scheme was followed for placebo, with respective dose matching volume. Hence, the adverse events are combinedly presented under 2 respective reporting groups, 'semaglutide 1.0 mg and placebo'.
Cardiac disorders Coronary artery disease	0.67% 1/150 • Number of events 1 • Week 0 to week 30 (treatment period) + 42 days (follow-up period). All the reported adverse events (AEs) are TEAEs. Results are based on the SAS. Treatment with semaglutide or placebo followed a fixed dose escalation. The maintenance dose of semaglutide 1.0 mg was reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg. The same fixed dose escalation scheme was followed for placebo, with respective dose matching volume. Hence, the adverse events are combinedly presented under 2 respective reporting groups, 'semaglutide 1.0 mg and placebo'.	0.00% 0/151 • Week 0 to week 30 (treatment period) + 42 days (follow-up period). All the reported adverse events (AEs) are TEAEs. Results are based on the SAS. Treatment with semaglutide or placebo followed a fixed dose escalation. The maintenance dose of semaglutide 1.0 mg was reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg. The same fixed dose escalation scheme was followed for placebo, with respective dose matching volume. Hence, the adverse events are combinedly presented under 2 respective reporting groups, 'semaglutide 1.0 mg and placebo'.
Infections and infestations Gastroenteritis bacterial	0.00% 0/150 • Week 0 to week 30 (treatment period) + 42 days (follow-up period). All the reported adverse events (AEs) are TEAEs. Results are based on the SAS. Treatment with semaglutide or placebo followed a fixed dose escalation. The maintenance dose of semaglutide 1.0 mg was reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg. The same fixed dose escalation scheme was followed for placebo, with respective dose matching volume. Hence, the adverse events are combinedly presented under 2 respective reporting groups, 'semaglutide 1.0 mg and placebo'.	0.66% 1/151 • Number of events 1 • Week 0 to week 30 (treatment period) + 42 days (follow-up period). All the reported adverse events (AEs) are TEAEs. Results are based on the SAS. Treatment with semaglutide or placebo followed a fixed dose escalation. The maintenance dose of semaglutide 1.0 mg was reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg. The same fixed dose escalation scheme was followed for placebo, with respective dose matching volume. Hence, the adverse events are combinedly presented under 2 respective reporting groups, 'semaglutide 1.0 mg and placebo'.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Laryngeal squamous cell carcinoma	0.00% 0/150 • Week 0 to week 30 (treatment period) + 42 days (follow-up period). All the reported adverse events (AEs) are TEAEs. Results are based on the SAS. Treatment with semaglutide or placebo followed a fixed dose escalation. The maintenance dose of semaglutide 1.0 mg was reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg. The same fixed dose escalation scheme was followed for placebo, with respective dose matching volume. Hence, the adverse events are combinedly presented under 2 respective reporting groups, 'semaglutide 1.0 mg and placebo'.	0.66% 1/151 • Number of events 1 • Week 0 to week 30 (treatment period) + 42 days (follow-up period). All the reported adverse events (AEs) are TEAEs. Results are based on the SAS. Treatment with semaglutide or placebo followed a fixed dose escalation. The maintenance dose of semaglutide 1.0 mg was reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg. The same fixed dose escalation scheme was followed for placebo, with respective dose matching volume. Hence, the adverse events are combinedly presented under 2 respective reporting groups, 'semaglutide 1.0 mg and placebo'.
Injury, poisoning and procedural complications Lower limb fracture	0.00% 0/150 • Week 0 to week 30 (treatment period) + 42 days (follow-up period). All the reported adverse events (AEs) are TEAEs. Results are based on the SAS. Treatment with semaglutide or placebo followed a fixed dose escalation. The maintenance dose of semaglutide 1.0 mg was reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg. The same fixed dose escalation scheme was followed for placebo, with respective dose matching volume. Hence, the adverse events are combinedly presented under 2 respective reporting groups, 'semaglutide 1.0 mg and placebo'.	0.66% 1/151 • Number of events 1 • Week 0 to week 30 (treatment period) + 42 days (follow-up period). All the reported adverse events (AEs) are TEAEs. Results are based on the SAS. Treatment with semaglutide or placebo followed a fixed dose escalation. The maintenance dose of semaglutide 1.0 mg was reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg. The same fixed dose escalation scheme was followed for placebo, with respective dose matching volume. Hence, the adverse events are combinedly presented under 2 respective reporting groups, 'semaglutide 1.0 mg and placebo'.
Infections and infestations Neurocysticercosis	0.67% 1/150 • Number of events 1 • Week 0 to week 30 (treatment period) + 42 days (follow-up period). All the reported adverse events (AEs) are TEAEs. Results are based on the SAS. Treatment with semaglutide or placebo followed a fixed dose escalation. The maintenance dose of semaglutide 1.0 mg was reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg. The same fixed dose escalation scheme was followed for placebo, with respective dose matching volume. Hence, the adverse events are combinedly presented under 2 respective reporting groups, 'semaglutide 1.0 mg and placebo'.	0.00% 0/151 • Week 0 to week 30 (treatment period) + 42 days (follow-up period). All the reported adverse events (AEs) are TEAEs. Results are based on the SAS. Treatment with semaglutide or placebo followed a fixed dose escalation. The maintenance dose of semaglutide 1.0 mg was reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg. The same fixed dose escalation scheme was followed for placebo, with respective dose matching volume. Hence, the adverse events are combinedly presented under 2 respective reporting groups, 'semaglutide 1.0 mg and placebo'.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.00% 0/150 • Week 0 to week 30 (treatment period) + 42 days (follow-up period). All the reported adverse events (AEs) are TEAEs. Results are based on the SAS. Treatment with semaglutide or placebo followed a fixed dose escalation. The maintenance dose of semaglutide 1.0 mg was reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg. The same fixed dose escalation scheme was followed for placebo, with respective dose matching volume. Hence, the adverse events are combinedly presented under 2 respective reporting groups, 'semaglutide 1.0 mg and placebo'.	0.66% 1/151 • Number of events 1 • Week 0 to week 30 (treatment period) + 42 days (follow-up period). All the reported adverse events (AEs) are TEAEs. Results are based on the SAS. Treatment with semaglutide or placebo followed a fixed dose escalation. The maintenance dose of semaglutide 1.0 mg was reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg. The same fixed dose escalation scheme was followed for placebo, with respective dose matching volume. Hence, the adverse events are combinedly presented under 2 respective reporting groups, 'semaglutide 1.0 mg and placebo'.
Musculoskeletal and connective tissue disorders Osteonecrosis	0.00% 0/150 • Week 0 to week 30 (treatment period) + 42 days (follow-up period). All the reported adverse events (AEs) are TEAEs. Results are based on the SAS. Treatment with semaglutide or placebo followed a fixed dose escalation. The maintenance dose of semaglutide 1.0 mg was reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg. The same fixed dose escalation scheme was followed for placebo, with respective dose matching volume. Hence, the adverse events are combinedly presented under 2 respective reporting groups, 'semaglutide 1.0 mg and placebo'.	0.66% 1/151 • Number of events 1 • Week 0 to week 30 (treatment period) + 42 days (follow-up period). All the reported adverse events (AEs) are TEAEs. Results are based on the SAS. Treatment with semaglutide or placebo followed a fixed dose escalation. The maintenance dose of semaglutide 1.0 mg was reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg. The same fixed dose escalation scheme was followed for placebo, with respective dose matching volume. Hence, the adverse events are combinedly presented under 2 respective reporting groups, 'semaglutide 1.0 mg and placebo'.
Eye disorders Retinal artery occlusion	0.67% 1/150 • Number of events 1 • Week 0 to week 30 (treatment period) + 42 days (follow-up period). All the reported adverse events (AEs) are TEAEs. Results are based on the SAS. Treatment with semaglutide or placebo followed a fixed dose escalation. The maintenance dose of semaglutide 1.0 mg was reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg. The same fixed dose escalation scheme was followed for placebo, with respective dose matching volume. Hence, the adverse events are combinedly presented under 2 respective reporting groups, 'semaglutide 1.0 mg and placebo'.	0.00% 0/151 • Week 0 to week 30 (treatment period) + 42 days (follow-up period). All the reported adverse events (AEs) are TEAEs. Results are based on the SAS. Treatment with semaglutide or placebo followed a fixed dose escalation. The maintenance dose of semaglutide 1.0 mg was reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg. The same fixed dose escalation scheme was followed for placebo, with respective dose matching volume. Hence, the adverse events are combinedly presented under 2 respective reporting groups, 'semaglutide 1.0 mg and placebo'.
Surgical and medical procedures Thyroidectomy	0.67% 1/150 • Number of events 1 • Week 0 to week 30 (treatment period) + 42 days (follow-up period). All the reported adverse events (AEs) are TEAEs. Results are based on the SAS. Treatment with semaglutide or placebo followed a fixed dose escalation. The maintenance dose of semaglutide 1.0 mg was reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg. The same fixed dose escalation scheme was followed for placebo, with respective dose matching volume. Hence, the adverse events are combinedly presented under 2 respective reporting groups, 'semaglutide 1.0 mg and placebo'.	0.00% 0/151 • Week 0 to week 30 (treatment period) + 42 days (follow-up period). All the reported adverse events (AEs) are TEAEs. Results are based on the SAS. Treatment with semaglutide or placebo followed a fixed dose escalation. The maintenance dose of semaglutide 1.0 mg was reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg. The same fixed dose escalation scheme was followed for placebo, with respective dose matching volume. Hence, the adverse events are combinedly presented under 2 respective reporting groups, 'semaglutide 1.0 mg and placebo'.
Nervous system disorders Transient ischaemic attack	0.67% 1/150 • Number of events 2 • Week 0 to week 30 (treatment period) + 42 days (follow-up period). All the reported adverse events (AEs) are TEAEs. Results are based on the SAS. Treatment with semaglutide or placebo followed a fixed dose escalation. The maintenance dose of semaglutide 1.0 mg was reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg. The same fixed dose escalation scheme was followed for placebo, with respective dose matching volume. Hence, the adverse events are combinedly presented under 2 respective reporting groups, 'semaglutide 1.0 mg and placebo'.	0.00% 0/151 • Week 0 to week 30 (treatment period) + 42 days (follow-up period). All the reported adverse events (AEs) are TEAEs. Results are based on the SAS. Treatment with semaglutide or placebo followed a fixed dose escalation. The maintenance dose of semaglutide 1.0 mg was reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg. The same fixed dose escalation scheme was followed for placebo, with respective dose matching volume. Hence, the adverse events are combinedly presented under 2 respective reporting groups, 'semaglutide 1.0 mg and placebo'.

Other adverse events

Measure	Semaglutide 1.0 mg n=150 participants at risk Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Placebo n=151 participants at risk Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Gastrointestinal disorders Nausea	19.3% 29/150 • Number of events 37 • Week 0 to week 30 (treatment period) + 42 days (follow-up period). All the reported adverse events (AEs) are TEAEs. Results are based on the SAS. Treatment with semaglutide or placebo followed a fixed dose escalation. The maintenance dose of semaglutide 1.0 mg was reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg. The same fixed dose escalation scheme was followed for placebo, with respective dose matching volume. Hence, the adverse events are combinedly presented under 2 respective reporting groups, 'semaglutide 1.0 mg and placebo'.	3.3% 5/151 • Number of events 7 • Week 0 to week 30 (treatment period) + 42 days (follow-up period). All the reported adverse events (AEs) are TEAEs. Results are based on the SAS. Treatment with semaglutide or placebo followed a fixed dose escalation. The maintenance dose of semaglutide 1.0 mg was reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg. The same fixed dose escalation scheme was followed for placebo, with respective dose matching volume. Hence, the adverse events are combinedly presented under 2 respective reporting groups, 'semaglutide 1.0 mg and placebo'.
Gastrointestinal disorders Vomiting	9.3% 14/150 • Number of events 21 • Week 0 to week 30 (treatment period) + 42 days (follow-up period). All the reported adverse events (AEs) are TEAEs. Results are based on the SAS. Treatment with semaglutide or placebo followed a fixed dose escalation. The maintenance dose of semaglutide 1.0 mg was reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg. The same fixed dose escalation scheme was followed for placebo, with respective dose matching volume. Hence, the adverse events are combinedly presented under 2 respective reporting groups, 'semaglutide 1.0 mg and placebo'.	2.0% 3/151 • Number of events 3 • Week 0 to week 30 (treatment period) + 42 days (follow-up period). All the reported adverse events (AEs) are TEAEs. Results are based on the SAS. Treatment with semaglutide or placebo followed a fixed dose escalation. The maintenance dose of semaglutide 1.0 mg was reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg. The same fixed dose escalation scheme was followed for placebo, with respective dose matching volume. Hence, the adverse events are combinedly presented under 2 respective reporting groups, 'semaglutide 1.0 mg and placebo'.
Gastrointestinal disorders Constipation	6.7% 10/150 • Number of events 10 • Week 0 to week 30 (treatment period) + 42 days (follow-up period). All the reported adverse events (AEs) are TEAEs. Results are based on the SAS. Treatment with semaglutide or placebo followed a fixed dose escalation. The maintenance dose of semaglutide 1.0 mg was reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg. The same fixed dose escalation scheme was followed for placebo, with respective dose matching volume. Hence, the adverse events are combinedly presented under 2 respective reporting groups, 'semaglutide 1.0 mg and placebo'.	0.00% 0/151 • Week 0 to week 30 (treatment period) + 42 days (follow-up period). All the reported adverse events (AEs) are TEAEs. Results are based on the SAS. Treatment with semaglutide or placebo followed a fixed dose escalation. The maintenance dose of semaglutide 1.0 mg was reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg. The same fixed dose escalation scheme was followed for placebo, with respective dose matching volume. Hence, the adverse events are combinedly presented under 2 respective reporting groups, 'semaglutide 1.0 mg and placebo'.
Eye disorders Diabetic retinopathy	1.3% 2/150 • Number of events 2 • Week 0 to week 30 (treatment period) + 42 days (follow-up period). All the reported adverse events (AEs) are TEAEs. Results are based on the SAS. Treatment with semaglutide or placebo followed a fixed dose escalation. The maintenance dose of semaglutide 1.0 mg was reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg. The same fixed dose escalation scheme was followed for placebo, with respective dose matching volume. Hence, the adverse events are combinedly presented under 2 respective reporting groups, 'semaglutide 1.0 mg and placebo'.	5.3% 8/151 • Number of events 9 • Week 0 to week 30 (treatment period) + 42 days (follow-up period). All the reported adverse events (AEs) are TEAEs. Results are based on the SAS. Treatment with semaglutide or placebo followed a fixed dose escalation. The maintenance dose of semaglutide 1.0 mg was reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg. The same fixed dose escalation scheme was followed for placebo, with respective dose matching volume. Hence, the adverse events are combinedly presented under 2 respective reporting groups, 'semaglutide 1.0 mg and placebo'.
Gastrointestinal disorders Diarrhoea	11.3% 17/150 • Number of events 21 • Week 0 to week 30 (treatment period) + 42 days (follow-up period). All the reported adverse events (AEs) are TEAEs. Results are based on the SAS. Treatment with semaglutide or placebo followed a fixed dose escalation. The maintenance dose of semaglutide 1.0 mg was reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg. The same fixed dose escalation scheme was followed for placebo, with respective dose matching volume. Hence, the adverse events are combinedly presented under 2 respective reporting groups, 'semaglutide 1.0 mg and placebo'.	6.0% 9/151 • Number of events 11 • Week 0 to week 30 (treatment period) + 42 days (follow-up period). All the reported adverse events (AEs) are TEAEs. Results are based on the SAS. Treatment with semaglutide or placebo followed a fixed dose escalation. The maintenance dose of semaglutide 1.0 mg was reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg. The same fixed dose escalation scheme was followed for placebo, with respective dose matching volume. Hence, the adverse events are combinedly presented under 2 respective reporting groups, 'semaglutide 1.0 mg and placebo'.
Infections and infestations Nasopharyngitis	5.3% 8/150 • Number of events 9 • Week 0 to week 30 (treatment period) + 42 days (follow-up period). All the reported adverse events (AEs) are TEAEs. Results are based on the SAS. Treatment with semaglutide or placebo followed a fixed dose escalation. The maintenance dose of semaglutide 1.0 mg was reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg. The same fixed dose escalation scheme was followed for placebo, with respective dose matching volume. Hence, the adverse events are combinedly presented under 2 respective reporting groups, 'semaglutide 1.0 mg and placebo'.	5.3% 8/151 • Number of events 11 • Week 0 to week 30 (treatment period) + 42 days (follow-up period). All the reported adverse events (AEs) are TEAEs. Results are based on the SAS. Treatment with semaglutide or placebo followed a fixed dose escalation. The maintenance dose of semaglutide 1.0 mg was reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg. The same fixed dose escalation scheme was followed for placebo, with respective dose matching volume. Hence, the adverse events are combinedly presented under 2 respective reporting groups, 'semaglutide 1.0 mg and placebo'.

Additional Information

Clinical Reporting Anchor and Disclosure (1452)

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