Trial Outcomes & Findings for A Research Study Comparing a New Medicine Oral Semaglutide to Sitagliptin in People With Type 2 Diabetes (NCT NCT04017832)

NCT ID: NCT04017832

Last Updated: 2024-10-01

Results Overview

Change in HbA1c from baseline to week 26 in percentage (%) point of HbA1c is presented. The outcome data was evaluated based on the on-treatment without rescue medication observation period and in-trial observation period. On-treatment without rescue medication observation period: from date of first dose of trial product following randomization and the end date which was the first date of any of the following: the last dose of trial product plus 3 days or initiation of rescue medication. In-trial observation period: the time period where participants were considered to be in the trial, regardless of discontinuation of trial product or initiation of rescue medication.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 1441 participants
• Primary outcome timeframe: From baseline to week 26
• Results posted on: 2024-10-01

Participant Flow

The trial was conducted at 90 sites in 8 countries as follows: Brazil (3 sites), China (58 sites), Czech Republic (4 sites); Hong Kong (1 site), Romania (6 sites), Serbia (7 sites), Taiwan (4 sites), and South Africa (7 sites).

This was a 26-week, multicenter, multinational trial with four arms comparing efficacy and safety of oral semaglutide 3 milligram (mg), 7 mg and 14 mg once-daily with sitagliptin 100 mg once-daily. Out of 1441 participants randomized in the study, 1438 participants were exposed to trial product.

Participant milestones

Measure	Oral Semaglutide 3 mg Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Overall Study STARTED	361	360	361	359
Overall Study Full Analysis Set	361	360	361	359
Overall Study Safety Analysis Set	361	358	361	358
Overall Study COMPLETED	345	342	335	350
Overall Study NOT COMPLETED	16	18	26	9

Reasons for withdrawal

Measure	Oral Semaglutide 3 mg Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Overall Study Withdrawal by Subject	13	12	21	7
Overall Study Lost to Follow-up	0	3	3	1
Overall Study Physician Decision	1	1	1	1
Overall Study Death	2	2	1	0

Baseline Characteristics

A Research Study Comparing a New Medicine Oral Semaglutide to Sitagliptin in People With Type 2 Diabetes

Baseline characteristics by cohort

Measure	Oral Semaglutide 3 mg n=361 Participants Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=360 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=361 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=359 Participants Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.	Total n=1441 Participants Total of all reporting groups
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Continuous	53.5 Years STANDARD_DEVIATION 11.2 • n=5 Participants	53.4 Years STANDARD_DEVIATION 10.8 • n=7 Participants	53.5 Years STANDARD_DEVIATION 10.5 • n=5 Participants	52.9 Years STANDARD_DEVIATION 10.9 • n=4 Participants	53.3 Years STANDARD_DEVIATION 10.8 • n=21 Participants
Sex: Female, Male Female	152 Participants n=5 Participants	147 Participants n=7 Participants	146 Participants n=5 Participants	156 Participants n=4 Participants	601 Participants n=21 Participants
Sex: Female, Male Male	209 Participants n=5 Participants	213 Participants n=7 Participants	215 Participants n=5 Participants	203 Participants n=4 Participants	840 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	17 Participants n=5 Participants	19 Participants n=7 Participants	15 Participants n=5 Participants	18 Participants n=4 Participants	69 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	344 Participants n=5 Participants	341 Participants n=7 Participants	346 Participants n=5 Participants	341 Participants n=4 Participants	1372 Participants n=21 Participants
Race/Ethnicity, Customized Other	8 Participants n=5 Participants	11 Participants n=7 Participants	18 Participants n=5 Participants	18 Participants n=4 Participants	55 Participants n=21 Participants
Race/Ethnicity, Customized White	73 Participants n=5 Participants	65 Participants n=7 Participants	67 Participants n=5 Participants	59 Participants n=4 Participants	264 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race/Ethnicity, Customized Asian	272 Participants n=5 Participants	270 Participants n=7 Participants	271 Participants n=5 Participants	271 Participants n=4 Participants	1084 Participants n=21 Participants
Race/Ethnicity, Customized Black or African American	8 Participants n=5 Participants	14 Participants n=7 Participants	5 Participants n=5 Participants	11 Participants n=4 Participants	38 Participants n=21 Participants
Race/Ethnicity, Customized NA	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants

PRIMARY outcome

Timeframe: From baseline to week 26

Population: Full analysis set (FAS) included all randomized participants. Overall Number of Participants Analyzed: participants with available data for this outcome measure and Number Analyzed: number of participants with available data for each specified category.

Change in HbA1c from baseline to week 26 in percentage (%) point of HbA1c is presented. The outcome data was evaluated based on the on-treatment without rescue medication observation period and in-trial observation period. On-treatment without rescue medication observation period: from date of first dose of trial product following randomization and the end date which was the first date of any of the following: the last dose of trial product plus 3 days or initiation of rescue medication. In-trial observation period: the time period where participants were considered to be in the trial, regardless of discontinuation of trial product or initiation of rescue medication.

Outcome measures

Measure	Oral Semaglutide 3 mg n=344 Participants Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=340 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=332 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=350 Participants Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Change From Baseline to Week 26 in Glycated Haemoglobin (HbA1c) (%) On-treatment observation period	-0.8 Percentage point of HbA1C Standard Deviation 1.0	-1.3 Percentage point of HbA1C Standard Deviation 1.0	-1.6 Percentage point of HbA1C Standard Deviation 1.0	-0.7 Percentage point of HbA1C Standard Deviation 1.0
Change From Baseline to Week 26 in Glycated Haemoglobin (HbA1c) (%) In-trial observation period	-0.8 Percentage point of HbA1C Standard Deviation 1.0	-1.3 Percentage point of HbA1C Standard Deviation 1.0	-1.5 Percentage point of HbA1C Standard Deviation 1.0	-0.7 Percentage point of HbA1C Standard Deviation 1.0

SECONDARY outcome

Timeframe: From baseline to week 26

Population: FAS included all randomized participants. Overall Number of Participants Analyzed: participants with available data for this outcome measure.

Change in fasting plasma glucose (FPG) from baseline to week 26 in millimole per liter (mmol/l) is presented. The outcome data was evaluated based on the on-treatment without rescue medication observation period: from date of first dose of trial product following randomization and the end date which was the first date of any of the following: the last dose of trial product plus 3 days or initiation of rescue medication.

Outcome measures

Measure	Oral Semaglutide 3 mg n=322 Participants Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=317 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=294 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=329 Participants Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Change From Baseline to Week 26 in Fasting Plasma Glucose (FPG)	-1.03 mmol/l Standard Deviation 2.11	-1.79 mmol/l Standard Deviation 2.20	-2.00 mmol/l Standard Deviation 2.42	-0.52 mmol/l Standard Deviation 2.36

SECONDARY outcome

Timeframe: From baseline to week 26

Population: FAS included all randomized participants. Overall Number of Participants Analyzed: participants with available data for this outcome measure.

Change from baseline in mean 7-point SMPG profile at week 26 is presented. SMPG was recorded at the following 7 time points: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after dinner and at bedtime. The outcome data was evaluated based on the on-treatment without rescue medication observation period: from date of first dose of trial product following randomization and the end date which was the first date of any of the following: the last dose of trial product plus 3 days or initiation of rescue medication.

Outcome measures

Measure	Oral Semaglutide 3 mg n=300 Participants Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=311 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=290 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=317 Participants Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Change From Baseline to Week 26 in Self-measured Plasma Glucose (SMPG) Profile: Mean 7-point Profile	-1.5 mmol/L Standard Deviation 2.2	-2.3 mmol/L Standard Deviation 2.2	-2.6 mmol/L Standard Deviation 2.2	-1.2 mmol/L Standard Deviation 2.4

SECONDARY outcome

Timeframe: From baseline to week 26

Population: FAS included all randomized participants. Overall Number of Participants Analyzed: participants with available data for this outcome measure.

Change from baseline in 7-point SMPG: Mean postprandial increment (over all meals) at week 26 is presented. The outcome data was evaluated based on the on-treatment without rescue medication observation period: from date of first dose of trial product following randomization and the end date which was the first date of any of the following: the last dose of trial product plus 3 days or initiation of rescue medication.

Outcome measures

Measure	Oral Semaglutide 3 mg n=301 Participants Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=311 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=290 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=317 Participants Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Change From Baseline to Week 26 in 7 Point SMPG Profile: Mean Postprandial Increment (Over All Meals)	-0.4 mmol/L Standard Deviation 2.0	-0.9 mmol/L Standard Deviation 1.9	-1.0 mmol/L Standard Deviation 2.1	-0.6 mmol/L Standard Deviation 2.1

SECONDARY outcome

Timeframe: At week 26

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

Number of participants who achieved HbA1c <7.0% (53 mmol/mol) (ADA target) is presented in category "Yes" and participants who could not achieve HbA1C <7.0 (53 mmol/mol) (ADA target) is presented in category "No". The outcome data was evaluated based on the on-treatment without rescue medication observation period: from date of first dose of trial product following randomization and the end date which was the first date of any of the following: the last dose of trial product plus 3 days or initiation of rescue medication.

Outcome measures

Measure	Oral Semaglutide 3 mg n=321 Participants Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=315 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=298 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=334 Participants Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Number of Participants Who Achieved HbA1c <7.0 % (53 mmol/Mol) (American Diabetes Association [ADA] Target) (Yes/no) Yes	139 Participants	213 Participants	226 Participants	122 Participants
Number of Participants Who Achieved HbA1c <7.0 % (53 mmol/Mol) (American Diabetes Association [ADA] Target) (Yes/no) No	182 Participants	102 Participants	72 Participants	212 Participants

SECONDARY outcome

Timeframe: At week 26

Population: FAS included all randomized participants. Overall Number of Participants Analyzed: participants with available data for this outcome measure.

Number of participants who achieved HbA1c equal to or below 6.5 percent (48 mmol/mol) (AACE target) (yes/no) is presented. The outcome data was evaluated based on the on-treatment without rescue medication observation period: from date of first dose of trial product following randomization and the end date which was the first date of any of the following: the last dose of trial product plus 3 days or initiation of rescue medication.

Outcome measures

Measure	Oral Semaglutide 3 mg n=321 Participants Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=315 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=298 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=334 Participants Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Number of Participants Who Achieved HbA1c Equal to or Below 6.5 Percent (48 mmol/Mol) (American Association of Clinical Endocrinologists (AACE) Target) (Yes/no) Yes	81 Participants	161 Participants	188 Participants	54 Participants
Number of Participants Who Achieved HbA1c Equal to or Below 6.5 Percent (48 mmol/Mol) (American Association of Clinical Endocrinologists (AACE) Target) (Yes/no) No	240 Participants	154 Participants	110 Participants	280 Participants

SECONDARY outcome

Timeframe: At week 26

Population: FAS included all randomized participants. Overall Number of Participants Analyzed: participants with available data for this outcome measure.

Number of participants who achieved HbA1c reduction equal to or above 1 percent-point (10.9 mmol/mol) (yes/no) is presented. The outcome data was evaluated based on the on-treatment without rescue medication observation period: from date of first dose of trial product following randomization and the end date which was the first date of any of the following: the last dose of trial product plus 3 days or initiation of rescue medication.

Outcome measures

Measure	Oral Semaglutide 3 mg n=321 Participants Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=314 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=298 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=334 Participants Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Number of Participants Who Achieved HbA1c Reduction Equal to or Above 1 Percent-point (10.9 mmol/Mol) (Yes/no) No	180 Participants	111 Participants	72 Participants	205 Participants
Number of Participants Who Achieved HbA1c Reduction Equal to or Above 1 Percent-point (10.9 mmol/Mol) (Yes/no) Yes	141 Participants	203 Participants	226 Participants	129 Participants

SECONDARY outcome

Timeframe: From baseline to week 31

Population: FAS included all randomized participants.

Time to rescue medication is presented as the number of participants who had taken rescue medication anytime from baseline to week 31. 'Rescue medication': use of new anti-diabetic medication as add-on to trial product and used for more than 21 days with the initiation at or after randomisation and before last day on trial product, and/or intensification of anti-diabetic medication (a more than 20% increase in dose relative to baseline) for more than 21 days with the intensification at or after randomisation and before last day on trial product. The outcome data was evaluated based on the on-treatment without rescue medication observation period: from date of first dose of trial product following randomization and the end date which was the first date of any of the following: the last dose of trial product plus 3 days or initiation of rescue medication.

Outcome measures

Measure	Oral Semaglutide 3 mg n=361 Participants Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=360 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=361 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=359 Participants Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Time to Rescue Medication	5 Participants	6 Participants	6 Participants	7 Participants

SECONDARY outcome

Timeframe: From baseline to week 26

Population: FAS included all randomized participants. Overall Number of Participants Analyzed: participants with available data for this outcome measure.

Change in body weight from baseline to week 26 in kg is presented. The outcome data was evaluated based on the on-treatment without rescue medication observation period: from date of first dose of trial product following randomization and the end date which was the first date of any of the following: the last dose of trial product plus 3 days or initiation of rescue medication.

Outcome measures

Measure	Oral Semaglutide 3 mg n=322 Participants Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=319 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=300 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=335 Participants Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Change From Baseline to Week 26 in Body Weight (Kilogram [kg])	-1.4 Kilogram Standard Deviation 3.0	-2.9 Kilogram Standard Deviation 3.3	-3.8 Kilogram Standard Deviation 3.7	-0.5 Kilogram Standard Deviation 2.6

SECONDARY outcome

Timeframe: From baseline to week 26

Population: FAS included all randomized participants. Overall Number of Participants Analyzed: participants with available data for this outcome measure.

Percentage change from baseline to week 26 in body weight is presented. The outcome data was evaluated based on the on-treatment without rescue medication observation period: from date of first dose of trial product following randomization and the end date which was the first date of any of the following: the last dose of trial product plus 3 days or initiation of rescue medication.

Outcome measures

Measure	Oral Semaglutide 3 mg n=322 Participants Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=319 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=300 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=335 Participants Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Percentage Change From Baseline to Week 26 in Body Weight	-2 Percentage change Standard Deviation 4	-4 Percentage change Standard Deviation 4	-5 Percentage change Standard Deviation 5	-1 Percentage change Standard Deviation 3

SECONDARY outcome

Timeframe: From baseline to week 26

Population: FAS included all randomized participants. Overall Number of Participants Analyzed: participants with available data for this outcome measure.

Change from baseline in BMI is presented. The outcome data was evaluated based on the on-treatment without rescue medication observation period: from date of first dose of trial product following randomization and the end date which was the first date of any of the following: the last dose of trial product plus 3 days or initiation of rescue medication.

Outcome measures

Measure	Oral Semaglutide 3 mg n=322 Participants Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=319 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=300 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=335 Participants Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Change From Baseline to Week 26 in Body Mass Index (BMI)	-0.5 Kilogram per square meter (kg/m^2) Standard Deviation 1.1	-1.1 Kilogram per square meter (kg/m^2) Standard Deviation 1.2	-1.4 Kilogram per square meter (kg/m^2) Standard Deviation 1.3	-0.2 Kilogram per square meter (kg/m^2) Standard Deviation 0.9

SECONDARY outcome

Timeframe: From baseline to week 26

Population: FAS included all randomized participants. Overall Number of Participants Analyzed: participants with available data for this outcome measure.

Change from baseline in waist circumference is presented. The outcome data was evaluated based on the on-treatment without rescue medication observation period: from date of first dose of trial product following randomization and the end date which was the first date of any of the following: the last dose of trial product plus 3 days or initiation of rescue medication.

Outcome measures

Measure	Oral Semaglutide 3 mg n=322 Participants Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=320 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=300 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=335 Participants Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Change From Baseline to Week 26 in Waist Circumference	-1.6 Centimeter Standard Deviation 4.0	-2.7 Centimeter Standard Deviation 4.4	-3.7 Centimeter Standard Deviation 4.1	-0.8 Centimeter Standard Deviation 3.4

SECONDARY outcome

Timeframe: From baseline to week 26

Population: FAS included all randomized participants. Overall Number of Participants Analyzed: participants with available data for this outcome measure.

Change from baseline in total cholesterol (measured in mmol/L) at week 26 is presented as ratio to baseline. The outcome data was evaluated based on the on-treatment without rescue medication observation period: from date of first dose of trial product following randomization up to the end date which was the first date of any of the following: the last dose of trial product plus 3 days or initiation of rescue medication.

Outcome measures

Measure	Oral Semaglutide 3 mg n=316 Participants Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=316 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=296 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=330 Participants Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Change From Baseline to Week 26 in Fasting Lipid Profile: Total Cholesterol (Ratio to Baseline)	1.00 Ratio of total cholesterol Geometric Coefficient of Variation 15.78	0.96 Ratio of total cholesterol Geometric Coefficient of Variation 17.34	0.96 Ratio of total cholesterol Geometric Coefficient of Variation 17.86	0.99 Ratio of total cholesterol Geometric Coefficient of Variation 19.69

SECONDARY outcome

Timeframe: From baseline to week 26

Population: FAS included all randomized participants. Overall Number of Participants Analyzed: participants with available data for this outcome measure.

Change from baseline in LDL cholesterol (measured in mmol/L) at week 26 is presented as ratio to baseline. The outcome data was evaluated based on the on-treatment without rescue medication observation period: from date of first dose of trial product following randomization up to the end date which was the first date of any of the following: the last dose of trial product plus 3 days or initiation of rescue medication.

Outcome measures

Measure	Oral Semaglutide 3 mg n=315 Participants Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=314 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=295 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=327 Participants Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Change From Baseline to Week 26 in Fasting Lipid Profile: Low-density Lipoprotein (LDL) Cholesterol (Ratio to Baseline)	1.02 Ratio of LDL cholesterol Geometric Coefficient of Variation 25.63	0.98 Ratio of LDL cholesterol Geometric Coefficient of Variation 28.70	0.98 Ratio of LDL cholesterol Geometric Coefficient of Variation 28.95	1.01 Ratio of LDL cholesterol Geometric Coefficient of Variation 30.12

SECONDARY outcome

Timeframe: From baseline to week 26

Population: FAS included all randomized participants. Overall Number of Participants Analyzed: participants with available data for this outcome measure.

Change from baseline in VLDL cholesterol (measured in mmol/L) at week 26 is presented as ratio to baseline. The outcome data was evaluated based on the on-treatment without rescue medication observation period: from date of first dose of trial product following randomization up to the end date which was the first date of any of the following: the last dose of trial product plus 3 days or initiation of rescue medication.

Outcome measures

Measure	Oral Semaglutide 3 mg n=315 Participants Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=315 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=295 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=327 Participants Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Change From Baseline to Week 26 in Fasting Lipid Profile: Very-low-density Lipoprotein (VLDL) Cholesterol (Ratio to Baseline)	1.05 Ratio of VLDL cholesterol Standard Deviation 0.45	0.94 Ratio of VLDL cholesterol Standard Deviation 0.37	0.94 Ratio of VLDL cholesterol Standard Deviation 0.41	0.98 Ratio of VLDL cholesterol Standard Deviation 0.43

SECONDARY outcome

Timeframe: From baseline to week 26

Population: FAS included all randomized participants. Overall Number of Participants Analyzed: participants with available data for this outcome measure.

Change from baseline in HDL Cholesterol (measured in mmol/L) at week 26 is presented as ratio to baseline. The outcome data was evaluated based on the on-treatment without rescue medication observation period: from date of first dose of trial product following randomization up to the end date which was the first date of any of the following: the last dose of trial product plus 3 days or initiation of rescue medication.

Outcome measures

Measure	Oral Semaglutide 3 mg n=313 Participants Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=313 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=293 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=323 Participants Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Change From Baseline to Week 26 in Fasting Lipid Profile: High-density Lipoprotein (HDL) Cholesterol (Ratio to Baseline)	1.02 Ratio of HDL cholesterol Geometric Coefficient of Variation 13.25	1.01 Ratio of HDL cholesterol Geometric Coefficient of Variation 14.42	1.00 Ratio of HDL cholesterol Geometric Coefficient of Variation 14.82	1.00 Ratio of HDL cholesterol Geometric Coefficient of Variation 16.03

SECONDARY outcome

Timeframe: From baseline to week 26

Population: FAS included all randomized participants. Overall Number of Participants Analyzed: participants with available data for this outcome measure.

Change from baseline in triglycerides (measured in mmol/L) at week 26 is presented as ratio to baseline. The outcome data was evaluated based on the on-treatment without rescue medication observation period: from date of first dose of trial product following randomization up to the end date which was the first date of any of the following: the last dose of trial product plus 3 days or initiation of rescue medication.

Outcome measures

Measure	Oral Semaglutide 3 mg n=315 Participants Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=315 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=295 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=327 Participants Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Change From Baseline to Week 26 in Fasting Lipid Profile: Triglycerides (Ratio to Baseline)	0.96 Ratio of triglycerides Geometric Coefficient of Variation 43.41	0.86 Ratio of triglycerides Geometric Coefficient of Variation 46.28	0.86 Ratio of triglycerides Geometric Coefficient of Variation 46.40	0.91 Ratio of triglycerides Geometric Coefficient of Variation 44.29

SECONDARY outcome

Timeframe: From baseline to week 26

Population: FAS included all randomized participants. Overall Number of Participants Analyzed: participants with available data for this outcome measure.

Change from baseline in free fatty acids (measured in mmol/L) at week 26 is presented as ratio to baseline. The outcome data was evaluated based on the on-treatment without rescue medication observation period: from date of first dose of trial product following randomization up to the end date which was the first date of any of the following: the last dose of trial product plus 3 days or initiation of rescue medication.

Outcome measures

Measure	Oral Semaglutide 3 mg n=308 Participants Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=308 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=290 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=318 Participants Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Change From Baseline to Week 26 in Fasting Lipid Profile: Free Fatty Acids (Ratio to Baseline)	0.95 Ratio of free fatty acids Geometric Coefficient of Variation 56.36	0.89 Ratio of free fatty acids Geometric Coefficient of Variation 56.46	0.87 Ratio of free fatty acids Geometric Coefficient of Variation 66.18	0.96 Ratio of free fatty acids Geometric Coefficient of Variation 62.50

SECONDARY outcome

Timeframe: From baseline to week 26

Population: FAS included all randomized participants. Overall Number of Participants Analyzed: participants with available data for this outcome measure and Number Analyzed: number of participants with available data for each specified category.

SF-36 v2.0 is a 36-item, patient-reported survey of patient health. SF-36 measures the participant's overall Health Related Quality of Life on 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health) and two component summary scores (physical component summary and mental component summary). Range of score for domains and component summary scores : 1-100 (Higher scores indicated a better health state). A positive change score indicates an improvement since baseline. Outcome data was evaluated based on the on-treatment without rescue medication observation period: from date of first dose of trial product following randomization up to end date which was first date of any of following: the last dose of trial product plus 3 days or initiation of rescue medication.

Outcome measures

Measure	Oral Semaglutide 3 mg n=322 Participants Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=320 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=299 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=334 Participants Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Change From Baseline to Week 26 in Short Form-36 Version 2 (SF-36v2) (Acute Version) Health Survey Physical Function	0.20 Score on a scale Standard Deviation 5.63	0.48 Score on a scale Standard Deviation 3.95	0.93 Score on a scale Standard Deviation 4.51	0.31 Score on a scale Standard Deviation 5.25
Change From Baseline to Week 26 in Short Form-36 Version 2 (SF-36v2) (Acute Version) Health Survey Role Physical	-0.47 Score on a scale Standard Deviation 6.72	-0.41 Score on a scale Standard Deviation 6.82	0.28 Score on a scale Standard Deviation 6.11	0.24 Score on a scale Standard Deviation 7.27
Change From Baseline to Week 26 in Short Form-36 Version 2 (SF-36v2) (Acute Version) Health Survey Bodily Pain	-0.06 Score on a scale Standard Deviation 8.44	-0.37 Score on a scale Standard Deviation 8.08	0.51 Score on a scale Standard Deviation 8.03	0.22 Score on a scale Standard Deviation 8.44
Change From Baseline to Week 26 in Short Form-36 Version 2 (SF-36v2) (Acute Version) Health Survey General Health	1.47 Score on a scale Standard Deviation 7.54	1.04 Score on a scale Standard Deviation 7.09	1.95 Score on a scale Standard Deviation 7.44	0.95 Score on a scale Standard Deviation 7.19
Change From Baseline to Week 26 in Short Form-36 Version 2 (SF-36v2) (Acute Version) Health Survey Vitality	0.44 Score on a scale Standard Deviation 6.68	0.84 Score on a scale Standard Deviation 6.64	1.21 Score on a scale Standard Deviation 7.66	0.33 Score on a scale Standard Deviation 7.28
Change From Baseline to Week 26 in Short Form-36 Version 2 (SF-36v2) (Acute Version) Health Survey Social Function	0.49 Score on a scale Standard Deviation 6.14	-0.36 Score on a scale Standard Deviation 6.45	0.17 Score on a scale Standard Deviation 5.92	0.10 Score on a scale Standard Deviation 6.36
Change From Baseline to Week 26 in Short Form-36 Version 2 (SF-36v2) (Acute Version) Health Survey Role Emotional	0.06 Score on a scale Standard Deviation 8.80	-0.66 Score on a scale Standard Deviation 8.37	0.23 Score on a scale Standard Deviation 8.26	0.03 Score on a scale Standard Deviation 8.40
Change From Baseline to Week 26 in Short Form-36 Version 2 (SF-36v2) (Acute Version) Health Survey Mental Health	0.51 Score on a scale Standard Deviation 7.01	0.33 Score on a scale Standard Deviation 6.71	0.70 Score on a scale Standard Deviation 7.34	-0.7 Score on a scale Standard Deviation 7.13
Change From Baseline to Week 26 in Short Form-36 Version 2 (SF-36v2) (Acute Version) Health Survey Physical Component	0.15 Score on a scale Standard Deviation 5.32	0.29 Score on a scale Standard Deviation 4.74	0.98 Score on a scale Standard Deviation 5.00	0.69 Score on a scale Standard Deviation 5.62
Change From Baseline to Week 26 in Short Form-36 Version 2 (SF-36v2) (Acute Version) Health Survey Mental Component	0.50 Score on a scale Standard Deviation 6.71	-0.07 Score on a scale Standard Deviation 6.50	0.44 Score on a scale Standard Deviation 6.75	-0.39 Score on a scale Standard Deviation 6.64

SECONDARY outcome

Timeframe: At week 26

Population: FAS included all randomized participants. Overall Number of Participants Analyzed: participants with available data for this outcome measure.

Number of participants who achieved body weight loss equal to or above 3 percent (yes/no) is presented. The outcome data was evaluated based on In-trial observation period: This observation period represented the time period where participants were considered to be in the trial, regardless of discontinuation of trial product or initiation of rescue medication. The in-trial observation period started at randomisation (as registered in the IWRS) and ended at the date of: The last direct participant-site contact, which was scheduled to take place 5 weeks after planned last dose of trial product at the follow-up visit; withdrawal for participants who withdrew their informed consent; The last participant-investigator contact as defined by the investigator for participants who were lost to follow-up; Death for participants who died before any of the above.

Outcome measures

Measure	Oral Semaglutide 3 mg n=343 Participants Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=339 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=332 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=350 Participants Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Number of Participants Who Achieved Body Weight Loss Equal to or Above 3 Percent (Yes/no) Yes	109 Participants	175 Participants	199 Participants	68 Participants
Number of Participants Who Achieved Body Weight Loss Equal to or Above 3 Percent (Yes/no) No	234 Participants	164 Participants	133 Participants	282 Participants

SECONDARY outcome

Timeframe: At week 26

Population: FAS included all randomized participants. Overall Number of Participants Analyzed: participants with available data for this outcome measure.

Number of participants who achieved body weight loss equal to or above 5 percent (yes/no) is presented. The outcome data was evaluated based on In-trial observation period: This observation period represented the time period where participants were considered to be in the trial, regardless of discontinuation of trial product or initiation of rescue medication. The in-trial observation period started at randomisation (as registered in the IWRS) and ended at the date of: The last direct participant-site contact, which was scheduled to take place 5 weeks after planned last dose of trial product at the follow-up visit; withdrawal for participants who withdrew their informed consent; The last participant-investigator contact as defined by the investigator for participants who were lost to follow-up; Death for participants who died before any of the above.

Outcome measures

Measure	Oral Semaglutide 3 mg n=343 Participants Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=342 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=333 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=351 Participants Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Number of Participants Who Achieved Body Weight Loss Equal to or Above 5 Percent (Yes/no) Yes	55 Participants	107 Participants	149 Participants	28 Participants
Number of Participants Who Achieved Body Weight Loss Equal to or Above 5 Percent (Yes/no) No	288 Participants	235 Participants	184 Participants	323 Participants

SECONDARY outcome

Timeframe: At week 26

Population: FAS included all randomized participants. Overall Number of Participants Analyzed: participants with available data for this outcome measure.

Number of participants who achieved body weight loss equal to or above 10 percent (yes/no). The outcome data was evaluated based on In-trial observation period: This observation period represented the time period where participants were considered to be in the trial, regardless of discontinuation of trial product or initiation of rescue medication. The in-trial observation period started at randomisation (as registered in the IWRS) and ended at the date of: The last direct participant-site contact, which was scheduled to take place 5 weeks after planned last dose of trial product at the follow-up visit; withdrawal for participants who withdrew their informed consent; The last participant-investigator contact as defined by the investigator for participants who were lost to follow-up; Death for participants who died before any of the above.

Outcome measures

Measure	Oral Semaglutide 3 mg n=343 Participants Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=342 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=333 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=351 Participants Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Number of Participants Who Achieved Body Weight Loss Equal to or Above 10 Percent (Yes/no) Yes	5 Participants	24 Participants	42 Participants	2 Participants
Number of Participants Who Achieved Body Weight Loss Equal to or Above 10 Percent (Yes/no) No	338 Participants	318 Participants	291 Participants	349 Participants

SECONDARY outcome

Timeframe: At week 26

Population: FAS included all randomized participants. Overall Number of Participants Analyzed: participants with available data for this outcome measure.

Number of participants who achieved HbA1c < 7.0 percent (53 mmol/mol) without hypoglycaemia (treatment-emergent severe or BG confirmed symptomatic hypoglycaemic episodes) and no body weight gain (yes/no) at week 26 is presented. The outcome data was evaluated based on In-trial observation period: This observation period represented the time period where participants were considered to be in the trial, regardless of discontinuation of trial product or initiation of rescue medication. The in-trial observation period started at randomisation (as registered in the IWRS) and ended at the date of: The last direct participant-site contact, which was scheduled to take place 5 weeks after planned last dose of trial product at the follow-up visit; withdrawal for participants who withdrew their informed consent; The last participant-investigator contact as defined by the investigator for participants who were lost to follow-up; Death for participants who died before any of the above.

Outcome measures

Measure	Oral Semaglutide 3 mg n=344 Participants Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=339 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=332 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=350 Participants Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Number of Participants Who Achieved HbA1c Below 7.0 Percent (53 mmol/Mol) Without Hypoglycaemia (Treatment-emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes) and no Body Weight Gain (Yes/no) Yes	114 Participants	195 Participants	222 Participants	79 Participants
Number of Participants Who Achieved HbA1c Below 7.0 Percent (53 mmol/Mol) Without Hypoglycaemia (Treatment-emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes) and no Body Weight Gain (Yes/no) No	230 Participants	144 Participants	110 Participants	271 Participants

SECONDARY outcome

Timeframe: At week 26

Population: FAS included all randomized participants. Overall Number of Participants Analyzed: participants with available data for this outcome measure.

Number of participants who achieved HbA1c reduction equal to or above 1 percent-point (10.9 mmol/mol) and body weight loss equal to or above 3 percent (yes/no) is presented. The outcome data was evaluated based on In-trial observation period: This observation period represented the time period where participants were considered to be in the trial, regardless of discontinuation of trial product or initiation of rescue medication. The in-trial observation period started at randomisation (as registered in the IWRS) and ended at the date of: The last direct participant-site contact, which was scheduled to take place 5 weeks after planned last dose of trial product at the follow-up visit; withdrawal for participants who withdrew their informed consent; The last participant-investigator contact as defined by the investigator for participants who were lost to follow-up; Death for participants who died before any of the above.

Outcome measures

Measure	Oral Semaglutide 3 mg n=344 Participants Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=339 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=332 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=350 Participants Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Number of Participants Who Achieved HbA1c Reduction Equal to or Above 1 Percent-point (10.9 mmol/Mol) and Body Weight Loss Equal to or Above 3 Percent (Yes/no) Yes	64 Participants	128 Participants	159 Participants	33 Participants
Number of Participants Who Achieved HbA1c Reduction Equal to or Above 1 Percent-point (10.9 mmol/Mol) and Body Weight Loss Equal to or Above 3 Percent (Yes/no) No	280 Participants	211 Participants	173 Participants	317 Participants

SECONDARY outcome

Timeframe: From baseline to week 31

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

An adverse event (AE) was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. AEs with onset during the on-treatment period correspond to treatment-emergent AEs (TEAEs). The outcome data was evaluated based on the on-treatment observation period: from date of first dose of trial product following randomization up to the first date of any of the following: follow-up visit, premature follow-up visit, last date on trial product plus 38 days or the end of the in-trial observation period.

Outcome measures

Measure	Oral Semaglutide 3 mg n=361 Participants Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=358 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=361 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=358 Participants Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Number of Treatment-emergent Adverse Events During Exposure to Trial Product	635 Events	741 Events	793 Events	643 Events

SECONDARY outcome

Timeframe: From baseline to week 31

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

Number of treatment-emergent severe or blood glucose (BG) confirmed symptomatic hypoglycaemic episodes during exposure to trial product is presented. Severe: requiring assistance from another person for recovery. 'BG-confirmed': hypoglycaemic episode with a plasma glucose value < 3.1 mmol/L (56 mg/dL); The outcome data was evaluated based on the on-treatment observation period: from date of first dose of trial product following randomization up to the first date of any of the following: follow-up visit, premature follow-up visit, last date on trial product plus 38 days or the end of the in-trial observation period.

Outcome measures

Measure	Oral Semaglutide 3 mg n=361 Participants Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=358 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=361 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=358 Participants Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Number of Treatment-emergent Severe or Blood Glucose Confirmed Symptomatic Hypoglycaemic Episodes During Exposure to Trial Product	2 Episodes	2 Episodes	2 Episodes	1 Episodes

SECONDARY outcome

Timeframe: From baseline to week 26

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

Change from baseline in hematology parameters such as basophils, eosinophils, lymphocytes, monocytes, and neutrophils were reported. The outcome data was evaluated based on the on-treatment observation period: from date of first dose of trial product following randomization up to the first date of any of the following: follow-up visit, premature follow-up visit, last date on trial product plus 38 days or the end of the in-trial observation period.

Outcome measures

Measure	Oral Semaglutide 3 mg n=310 Participants Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=305 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=290 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=320 Participants Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Change From Baseline to Week 26 in Haematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils Basophils	0.01 10^9 cells per liter Standard Deviation 0.05	0.01 10^9 cells per liter Standard Deviation 0.05	0.00 10^9 cells per liter Standard Deviation 0.04	0.00 10^9 cells per liter Standard Deviation 0.05
Change From Baseline to Week 26 in Haematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils Eosinophils	0.00 10^9 cells per liter Standard Deviation 0.11	0.00 10^9 cells per liter Standard Deviation 0.09	-0.01 10^9 cells per liter Standard Deviation 0.25	-0.00 10^9 cells per liter Standard Deviation 0.11
Change From Baseline to Week 26 in Haematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils Lymphocytes	-0.03 10^9 cells per liter Standard Deviation 0.46	0.01 10^9 cells per liter Standard Deviation 0.40	0.00 10^9 cells per liter Standard Deviation 0.52	0.00 10^9 cells per liter Standard Deviation 0.39
Change From Baseline to Week 26 in Haematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils Monocytes	0.01 10^9 cells per liter Standard Deviation 0.15	0.01 10^9 cells per liter Standard Deviation 0.13	0.01 10^9 cells per liter Standard Deviation 0.14	0.02 10^9 cells per liter Standard Deviation 0.12
Change From Baseline to Week 26 in Haematology Parameters: Basophils, Eosinophils, Lymphocytes, Monocytes, and Neutrophils Neutrophils	0.03 10^9 cells per liter Standard Deviation 1.08	0.13 10^9 cells per liter Standard Deviation 1.15	0.10 10^9 cells per liter Standard Deviation 1.22	0.31 10^9 cells per liter Standard Deviation 1.17

SECONDARY outcome

Timeframe: From baseline to week 26

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

Change from baseline in Haematocrit at week 26 is reported as ratio to baseline. The outcome data was evaluated based on the on-treatment observation period: from date of first dose of trial product following randomization up to the first date of any of the following: follow-up visit, premature follow-up visit, last date on trial product plus 38 days or the end of the in-trial observation period.

Outcome measures

Measure	Oral Semaglutide 3 mg n=310 Participants Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=306 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=290 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=320 Participants Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Change From Baseline to Week 26 in Haematology Parameter: Haematocrit (Ratio to Baseline)	1.01 Ratio of haematocrit Geometric Coefficient of Variation 6.76	1.00 Ratio of haematocrit Geometric Coefficient of Variation 6.64	1.00 Ratio of haematocrit Geometric Coefficient of Variation 6.21	1.00 Ratio of haematocrit Geometric Coefficient of Variation 6.35

SECONDARY outcome

Timeframe: From baseline to week 26

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

Change from baseline in Haemoglobin at week 26 is reported as ratio to baseline. The outcome data was evaluated based on the on-treatment observation period: from date of first dose of trial product following randomization up to the first date of any of the following: follow-up visit, premature follow-up visit, last date on trial product plus 38 days or the end of the in-trial observation period.

Outcome measures

Measure	Oral Semaglutide 3 mg n=310 Participants Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=306 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=290 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=320 Participants Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Change From Baseline to Week 26 in Haematology Parameter: Haemoglobin (Ratio to Baseline)	1.00 Ratio of haemoglobin Geometric Coefficient of Variation 5.71	1.00 Ratio of haemoglobin Geometric Coefficient of Variation 6.04	1.00 Ratio of haemoglobin Geometric Coefficient of Variation 5.47	1.00 Ratio of haemoglobin Geometric Coefficient of Variation 6.11

SECONDARY outcome

Timeframe: From baseline to week 26

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

Change from baseline in Leucocytes at week 26 is reported as ratio to baseline. The outcome data was evaluated based on the on-treatment observation period: from date of first dose of trial product following randomization up to the first date of any of the following: follow-up visit, premature follow-up visit, last date on trial product plus 38 days or the end of the in-trial observation period.

Outcome measures

Measure	Oral Semaglutide 3 mg n=310 Participants Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=306 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=290 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=320 Participants Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Change From Baseline to Week 26 in Haematology Parameter: Leucocytes (Ratio to Baseline)	1.01 Ratio of leucocytes Geometric Coefficient of Variation 19.28	1.02 Ratio of leucocytes Geometric Coefficient of Variation 19.54	1.01 Ratio of leucocytes Geometric Coefficient of Variation 21.24	1.04 Ratio of leucocytes Geometric Coefficient of Variation 17.87

SECONDARY outcome

Timeframe: From baseline to week 26

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

Change from baseline in thrombocytes at week 26 is reported as ratio to baseline. The outcome data was evaluated based on the on-treatment observation period: from date of first dose of trial product following randomization up to the first date of any of the following: follow-up visit, premature follow-up visit, last date on trial product plus 38 days or the end of the in-trial observation period.

Outcome measures

Measure	Oral Semaglutide 3 mg n=305 Participants Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=305 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=285 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=316 Participants Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Change From Baseline to Week 26 in Haematology Parameter: Thrombocytes (Ratio to Baseline)	0.99 Ratio of thrombocytes Geometric Coefficient of Variation 14.53	0.99 Ratio of thrombocytes Geometric Coefficient of Variation 16.65	0.99 Ratio of thrombocytes Geometric Coefficient of Variation 16.65	0.97 Ratio of thrombocytes Geometric Coefficient of Variation 15.65

SECONDARY outcome

Timeframe: From baseline to week 26

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

Change from baseline in calcium (total) (measured in mmol/L) at week 26 is presented as ratio to baseline. The outcome data was evaluated based on the on-treatment observation period: from date of first dose of trial product following randomization up to the first date of any of the following: follow-up visit, premature follow-up visit, last date on trial product plus 38 days or the end of the in-trial observation period.

Outcome measures

Measure	Oral Semaglutide 3 mg n=320 Participants Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=322 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=301 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=336 Participants Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Change From Baseline to Week 26 in Biochemistry Parameter: Calcium (Total) (Ratio to Baseline)	0.98 Ratio of calcium Geometric Coefficient of Variation 4.40	0.98 Ratio of calcium Geometric Coefficient of Variation 4.74	0.99 Ratio of calcium Geometric Coefficient of Variation 4.80	0.98 Ratio of calcium Geometric Coefficient of Variation 4.40

SECONDARY outcome

Timeframe: From baseline to week 26

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

Change from baseline in potassium (measured in mmol/L) at week 26 is presented as ratio to baseline. The outcome data was evaluated based on the on-treatment observation period: from date of first dose of trial product following randomization up to the first date of any of the following: follow-up visit, premature follow-up visit, last date on trial product plus 38 days or the end of the in-trial observation period.

Outcome measures

Measure	Oral Semaglutide 3 mg n=319 Participants Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=322 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=301 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=335 Participants Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Change From Baseline to Week 26 in Biochemistry Parameter: Potassium (Ratio to Baseline)	1.00 Ratio of potassium Geometric Coefficient of Variation 8.51	1.00 Ratio of potassium Geometric Coefficient of Variation 8.34	1.00 Ratio of potassium Geometric Coefficient of Variation 8.96	1.01 Ratio of potassium Geometric Coefficient of Variation 9.28

SECONDARY outcome

Timeframe: From baseline to week 26

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

Change from baseline in sodium (measured in mmol/L) at week 26 is presented as ratio to baseline. The outcome data was evaluated based on the on-treatment observation period: from date of first dose of trial product following randomization up to the first date of any of the following: follow-up visit, premature follow-up visit, last date on trial product plus 38 days or the end of the in-trial observation period.

Outcome measures

Measure	Oral Semaglutide 3 mg n=319 Participants Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=322 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=301 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=335 Participants Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Change From Baseline to Week 26 in Biochemistry Parameter: Sodium (Ratio to Baseline)	1.00 Ratio of sodium Geometric Coefficient of Variation 1.58	1.00 Ratio of sodium Geometric Coefficient of Variation 1.40	1.00 Ratio of sodium Geometric Coefficient of Variation 1.49	1.00 Ratio of sodium Geometric Coefficient of Variation 1.59

SECONDARY outcome

Timeframe: From baseline to week 26

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

Change from baseline in urea (measured in mmol/L) at week 26 is presented as ratio to baseline. The outcome data was evaluated based on the on-treatment observation period: from date of first dose of trial product following randomization up to the first date of any of the following: follow-up visit, premature follow-up visit, last date on trial product plus 38 days or the end of the in-trial observation period.

Outcome measures

Measure	Oral Semaglutide 3 mg n=320 Participants Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=322 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=301 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=336 Participants Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Change From Baseline to Week 26 in Biochemistry Parameter: Urea (Ratio to Baseline)	1.00 Ratio of urea Geometric Coefficient of Variation 26.29	0.99 Ratio of urea Geometric Coefficient of Variation 25.61	0.98 Ratio of urea Geometric Coefficient of Variation 23.78	1.03 Ratio of urea Geometric Coefficient of Variation 22.67

SECONDARY outcome

Timeframe: From baseline to week 26

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

Change from baseline in Albumin (measured in grams per deciliter [g/dL]) at week 26 is presented as ratio to baseline. The outcome data was evaluated based on the on-treatment observation period: from date of first dose of trial product following randomization up to the first date of any of the following: follow-up visit, premature follow-up visit, last date on trial product plus 38 days or the end of the in-trial observation period.

Outcome measures

Measure	Oral Semaglutide 3 mg n=320 Participants Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=323 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=303 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=337 Participants Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Change From Baseline to Week 26 in Biochemistry Parameter: Albumin (Ratio to Baseline)	0.99 Ratio of albumin Geometric Coefficient of Variation 4.40	0.99 Ratio of albumin Geometric Coefficient of Variation 4.57	0.99 Ratio of albumin Geometric Coefficient of Variation 5.22	0.99 Ratio of albumin Geometric Coefficient of Variation 5.05

SECONDARY outcome

Timeframe: From baseline to week 26

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

Change from baseline in calcitonin (measured in picograms per milliliter [pg/ml]) at week 26 is presented as ratio to baseline. The outcome data was evaluated based on the on-treatment observation period: from date of first dose of trial product following randomization up to the first date of any of the following: follow-up visit, premature follow-up visit, last date on trial product plus 38 days or the end of the in-trial observation period.

Outcome measures

Measure	Oral Semaglutide 3 mg n=324 Participants Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=324 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=301 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=335 Participants Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Change From Baseline to Week 26 in Calcitonin (Ratio to Baseline)	1.00 Ratio of calcitonin Geometric Coefficient of Variation 38.33	1.05 Ratio of calcitonin Geometric Coefficient of Variation 35.56	1.02 Ratio of calcitonin Geometric Coefficient of Variation 36.49	1.01 Ratio of calcitonin Geometric Coefficient of Variation 31.96

SECONDARY outcome

Timeframe: From baseline to week 26

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

Change from baseline in pulse rate is presented. The outcome data was evaluated based on the on-treatment observation period: from date of first dose of trial product following randomization up to the first date of any of the following: follow-up visit, premature follow-up visit, last date on trial product plus 38 days or the end of the in-trial observation period.

Outcome measures

Measure	Oral Semaglutide 3 mg n=361 Participants Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=358 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=361 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=358 Participants Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Change From Baseline to Week 26 in Vital Signs: Pulse Rate	78 Beats per minute (beats/min) Standard Deviation 10	78 Beats per minute (beats/min) Standard Deviation 11	78 Beats per minute (beats/min) Standard Deviation 10	78 Beats per minute (beats/min) Standard Deviation 10

SECONDARY outcome

Timeframe: From baseline to week 26

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

Change from baseline in systolic blood pressure is presented. The outcome data was evaluated based on the on-treatment observation period: from date of first dose of trial product following randomization up to the first date of any of the following: follow-up visit, premature follow-up visit, last date on trial product plus 38 days or the end of the in-trial observation period.

Outcome measures

Measure	Oral Semaglutide 3 mg n=361 Participants Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=358 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=361 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=358 Participants Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Change From Baseline to Week 26 in Vital Signs: Systolic Blood Pressure	131 Millimeter of mercury (mmHg) Standard Deviation 16	132 Millimeter of mercury (mmHg) Standard Deviation 15	130 Millimeter of mercury (mmHg) Standard Deviation 14	130 Millimeter of mercury (mmHg) Standard Deviation 14

SECONDARY outcome

Timeframe: From baseline to week 26

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

Change from baseline in diastolic blood pressure is presented. The outcome data was evaluated based on the on-treatment observation period: from date of first dose of trial product following randomization up to the first date of any of the following: follow-up visit, premature follow-up visit, last date on trial product plus 38 days or the end of the in-trial observation period.

Outcome measures

Measure	Oral Semaglutide 3 mg n=361 Participants Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=358 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=361 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=358 Participants Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Change From Baseline to Week 26 in Vital Signs: Diastolic Blood Pressure	83 Millimeter of mercury (mmHg) Standard Deviation 10	84 Millimeter of mercury (mmHg) Standard Deviation 9	83 Millimeter of mercury (mmHg) Standard Deviation 10	83 Millimeter of mercury (mmHg) Standard Deviation 9

SECONDARY outcome

Timeframe: From baseline to week 26

Population: SAS included all participants exposed to at least one dose of trial product. Overall Number of Participants Analyzed: participants with available data for this outcome measure and Number Analyzed: number of participants with available data for each specified category.

Change from baseline in ECG category at week 26 is presented. Change from baseline results are presented as shift in findings categorized as: normal, abnormal and not clinically significant (NCS), and abnormal and clinically significant (CS). The outcome data was evaluated based on the on-treatment observation period: from date of first dose of trial product following randomization up to the first date of any of the following: follow-up visit, premature follow-up visit, last date on trial product plus 38 days or the end of the in-trial observation period.

Outcome measures

Measure	Oral Semaglutide 3 mg n=328 Participants Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=328 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=303 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=344 Participants Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Change From Baseline to Week 26 in Electrocardiogram (ECG) Category Normal (Baseline) to normal (week 26)	174 Participants	163 Participants	165 Participants	175 Participants
Change From Baseline to Week 26 in Electrocardiogram (ECG) Category Normal (Baseline) to abnormal NCS (week 26)	21 Participants	30 Participants	29 Participants	17 Participants
Change From Baseline to Week 26 in Electrocardiogram (ECG) Category Normal (Baseline) to abnormal CS (week 26)	8 Participants	3 Participants	10 Participants	5 Participants
Change From Baseline to Week 26 in Electrocardiogram (ECG) Category Abnormal NCS (Baseline) to normal (week 26)	26 Participants	27 Participants	26 Participants	43 Participants
Change From Baseline to Week 26 in Electrocardiogram (ECG) Category Abnormal NCS (Baseline) to abnormal NCS (week 26)	56 Participants	61 Participants	40 Participants	64 Participants
Change From Baseline to Week 26 in Electrocardiogram (ECG) Category Abnormal NCS (Baseline) to abnormal CS (week 26)	3 Participants	3 Participants	5 Participants	2 Participants
Change From Baseline to Week 26 in Electrocardiogram (ECG) Category Abnormal CS (Baseline) to normal (week 26)	8 Participants	13 Participants	7 Participants	6 Participants
Change From Baseline to Week 26 in Electrocardiogram (ECG) Category Abnormal CS (Baseline) to abnormal NCS (week 26)	5 Participants	3 Participants	4 Participants	9 Participants
Change From Baseline to Week 26 in Electrocardiogram (ECG) Category Abnormal CS (Baseline) to abnormal CS (week 26)	27 Participants	25 Participants	17 Participants	23 Participants

SECONDARY outcome

Timeframe: Baseline and week 26

Population: SAS included all participants exposed to at least one dose of trial product. Number Analyzed: number of participants with available data for each specified category.

The physical examination values for different body systems at baseline and week 26 are presented. The investigator interpreted the results and categorised them as: normal, abnormal NCS or abnormal CS. The physical examination are presented for the following body systems: cardiovascular system; central and peripheral nervous system; gastrointestinal system, including mouth; general appearance; head, ears, eyes, nose, throat, neck; lymph node palpation; musculoskeletal system; respiratory system; skin; and thyroid gland. The outcome data was evaluated based on the on-treatment observation period: from date of first dose of trial product following randomization up to the first date of any of the following: follow-up visit, premature follow-up visit, last date on trial product plus 38 days or the end of the in-trial observation period.

Outcome measures

Measure	Oral Semaglutide 3 mg n=361 Participants Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=358 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=361 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=358 Participants Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Physical Examination Category Central and Peripheral Nervous System - Abnormal NCS (Week 26)	2 Participants	3 Participants	2 Participants	2 Participants
Physical Examination Category Cardiovascular system - Normal (Baseline)	354 Participants	353 Participants	355 Participants	356 Participants
Physical Examination Category Cardiovascular system - abnormal NCS (Baseline)	5 Participants	4 Participants	6 Participants	2 Participants
Physical Examination Category Cardiovascular system - Abnormal CS (Baseline)	2 Participants	1 Participants	0 Participants	0 Participants
Physical Examination Category Cardiovascular system -Normal (Week 26)	319 Participants	322 Participants	301 Participants	339 Participants
Physical Examination Category Cardiovascular system - Abnormal NCS (Week 26)	5 Participants	2 Participants	3 Participants	2 Participants
Physical Examination Category Cardiovascular system - Abnormal CS (Week 26)	3 Participants	2 Participants	1 Participants	0 Participants
Physical Examination Category Central and Peripheral Nervous System - Normal (Baseline)	355 Participants	351 Participants	358 Participants	357 Participants
Physical Examination Category Central and Peripheral Nervous System - Abnormal NCS (Baseline)	2 Participants	5 Participants	3 Participants	1 Participants
Physical Examination Category Central and Peripheral Nervous System - Abnormal CS (Baseline)	4 Participants	2 Participants	0 Participants	0 Participants
Physical Examination Category Central and Peripheral Nervous System - Normal (Week 26)	322 Participants	321 Participants	302 Participants	339 Participants
Physical Examination Category Central and Peripheral Nervous System - Abnormal CS (Week 26)	2 Participants	2 Participants	1 Participants	0 Participants
Physical Examination Category Gastrointestinal System incl. Mouth - Normal (Baseline)	350 Participants	343 Participants	353 Participants	346 Participants
Physical Examination Category Gastrointestinal System incl. Mouth - Abnormal NCS (Baseline)	10 Participants	14 Participants	7 Participants	11 Participants
Physical Examination Category Gastrointestinal System incl. Mouth - Abnormal CS (Baseline)	1 Participants	1 Participants	1 Participants	1 Participants
Physical Examination Category Gastrointestinal System incl. Mouth - Normal (Week 26)	314 Participants	315 Participants	300 Participants	329 Participants
Physical Examination Category Gastrointestinal System incl. Mouth - Abnormal NCS (Week 26)	12 Participants	10 Participants	4 Participants	10 Participants
Physical Examination Category Gastrointestinal System incl. Mouth - Abnormal CS (Week 26)	0 Participants	1 Participants	1 Participants	2 Participants
Physical Examination Category General Appearance - Normal (Baseline)	329 Participants	325 Participants	328 Participants	328 Participants
Physical Examination Category General Appearance - Abnormal NCS (Baseline)	25 Participants	27 Participants	21 Participants	22 Participants
Physical Examination Category General Appearance - Abnormal CS (Baseline)	7 Participants	6 Participants	12 Participants	8 Participants
Physical Examination Category General Appearance - Normal (Week 26)	300 Participants	295 Participants	280 Participants	313 Participants
Physical Examination Category General Appearance - Abnormal NCS (Week 26)	21 Participants	27 Participants	19 Participants	21 Participants
Physical Examination Category General Appearance - Abnormal CS (Week 26)	6 Participants	4 Participants	6 Participants	7 Participants
Physical Examination Category Head, Ears, Eyes, Nose, Throat, Neck - Normal (Baseline)	348 Participants	349 Participants	351 Participants	344 Participants
Physical Examination Category Head, Ears, Eyes, Nose, Throat, Neck - Abnormal NCS (Baseline)	9 Participants	8 Participants	5 Participants	6 Participants
Physical Examination Category Head, Ears, Eyes, Nose, Throat, Neck - Abnormal CS (Baseline)	4 Participants	0 Participants	4 Participants	5 Participants
Physical Examination Category Head, Ears, Eyes, Nose, Throat, Neck - Normal (Week 26)	322 Participants	319 Participants	297 Participants	330 Participants
Physical Examination Category Head, Ears, Eyes, Nose, Throat, Neck - Abnormal NCS (Week 26)	3 Participants	5 Participants	4 Participants	4 Participants
Physical Examination Category Head, Ears, Eyes, Nose, Throat, Neck - Abnormal CS (Week 26)	2 Participants	1 Participants	2 Participants	5 Participants
Physical Examination Category Lymph Node Palpation - Normal (Baseline)	361 Participants	353 Participants	357 Participants	357 Participants
Physical Examination Category Lymph Node Palpation - Abnormal NCS (Baseline)	0 Participants	5 Participants	3 Participants	1 Participants
Physical Examination Category Lymph Node Palpation - Abnormal CS (Baseline)	0 Participants	0 Participants	1 Participants	0 Participants
Physical Examination Category Lymph Node Palpation - Normal (Week 26)	325 Participants	323 Participants	304 Participants	341 Participants
Physical Examination Category Lymph Node Palpation - Abnormal NCS (Week 26)	1 Participants	3 Participants	1 Participants	0 Participants
Physical Examination Category Lymph Node Palpation - Abnormal CS (Week 26)	0 Participants	0 Participants	0 Participants	0 Participants
Physical Examination Category Musculoskeletal System - Normal (Baseline)	344 Participants	345 Participants	351 Participants	352 Participants
Physical Examination Category Musculoskeletal System - Abnormal NCS (Baseline)	13 Participants	8 Participants	7 Participants	4 Participants
Physical Examination Category Musculoskeletal System - Abnormal CS (Baseline)	4 Participants	5 Participants	3 Participants	2 Participants
Physical Examination Category Musculoskeletal System - Normal (Week 26)	314 Participants	319 Participants	301 Participants	335 Participants
Physical Examination Category Musculoskeletal System - Abnormal NCS (Week 26)	6 Participants	4 Participants	2 Participants	3 Participants
Physical Examination Category Musculoskeletal System - Abnormal CS (Week 26)	6 Participants	3 Participants	2 Participants	3 Participants
Physical Examination Category Respiratory System - Normal (Baseline)	355 Participants	355 Participants	359 Participants	357 Participants
Physical Examination Category Respiratory System -Abnormal NCS (Baseline)	3 Participants	3 Participants	1 Participants	1 Participants
Physical Examination Category Respiratory System - Abnormal CS (Baseline)	3 Participants	0 Participants	1 Participants	0 Participants
Physical Examination Category Respiratory System - Normal (Week 26)	324 Participants	325 Participants	305 Participants	341 Participants
Physical Examination Category Respiratory System - Abnormal NCS (Week 26)	2 Participants	1 Participants	0 Participants	0 Participants
Physical Examination Category Respiratory System - Abnormal CS (Week 26)	0 Participants	0 Participants	0 Participants	0 Participants
Physical Examination Category Skin - Normal (Baseline)	282 Participants	282 Participants	296 Participants	277 Participants
Physical Examination Category Skin - Abnormal NCS (Baseline)	71 Participants	65 Participants	54 Participants	65 Participants
Physical Examination Category Skin - Abnormal CS (Baseline)	8 Participants	11 Participants	11 Participants	16 Participants
Physical Examination Category Skin - Normal (Week 26)	260 Participants	263 Participants	256 Participants	267 Participants
Physical Examination Category Skin - Abnormal NCS (Week 26)	60 Participants	52 Participants	42 Participants	60 Participants
Physical Examination Category Skin - Abnormal CS (Week 26)	7 Participants	11 Participants	7 Participants	14 Participants
Physical Examination Category Thyroid Gland - Normal (Baseline)	356 Participants	351 Participants	358 Participants	350 Participants
Physical Examination Category Thyroid Gland - Abnormal NCS (Baseline)	4 Participants	4 Participants	1 Participants	4 Participants
Physical Examination Category Thyroid Gland - Abnormal CS (Baseline)	1 Participants	3 Participants	2 Participants	4 Participants
Physical Examination Category Thyroid Gland - Normal (Week 26)	322 Participants	319 Participants	304 Participants	337 Participants
Physical Examination Category Thyroid Gland - Abnormal NCS (Week 26)	3 Participants	4 Participants	0 Participants	2 Participants
Physical Examination Category Thyroid Gland - Abnormal CS (Week 26)	2 Participants	3 Participants	1 Participants	2 Participants

SECONDARY outcome

Timeframe: From baseline to week 26

Population: SAS included all participants exposed to at least one dose of trial product. Number Analyzed: number of participants with available data for each specified category.

The eye examination category at baseline and week 26 are presented. The investigator interpreted the results and categorised them as: normal, abnormal NCS or abnormal CS. The outcome data was evaluated based on the on-treatment observation period: from date of first dose of trial product following randomization up to the first date of any of the following: follow-up visit, premature follow-up visit, last date on trial product plus 38 days or the end of the in-trial observation period.

Outcome measures

Measure	Oral Semaglutide 3 mg n=361 Participants Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=358 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=361 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=358 Participants Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Change From Baseline to Week 26 in Eye Examination Category Right Eye Ophthalmoscopy - Normal (Week 26)	223 Participants	218 Participants	220 Participants	233 Participants
Change From Baseline to Week 26 in Eye Examination Category Right Eye Ophthalmoscopy - Abnormal NCS (Week 26)	49 Participants	49 Participants	45 Participants	43 Participants
Change From Baseline to Week 26 in Eye Examination Category Right Eye Ophthalmoscopy - Abnormal CS (Week 26)	53 Participants	55 Participants	36 Participants	59 Participants
Change From Baseline to Week 26 in Eye Examination Category Left Eye Ophthalmoscopy - Normal (Baseline)	245 Participants	240 Participants	254 Participants	248 Participants
Change From Baseline to Week 26 in Eye Examination Category Left Eye Ophthalmoscopy - Abnormal NCS (Baseline)	60 Participants	51 Participants	61 Participants	52 Participants
Change From Baseline to Week 26 in Eye Examination Category Left Eye Ophthalmoscopy - Abnormal CS (Baseline)	56 Participants	67 Participants	46 Participants	58 Participants
Change From Baseline to Week 26 in Eye Examination Category Left Eye Ophthalmoscopy - Normal (Week 26)	221 Participants	226 Participants	217 Participants	240 Participants
Change From Baseline to Week 26 in Eye Examination Category Left Eye Ophthalmoscopy -Abnormal NCS (Week 26)	49 Participants	44 Participants	50 Participants	39 Participants
Change From Baseline to Week 26 in Eye Examination Category Left Eye Ophthalmoscopy - Abnormal CS (Week 26)	55 Participants	53 Participants	34 Participants	56 Participants
Change From Baseline to Week 26 in Eye Examination Category Right Eye Ophthalmoscopy - Normal (Baseline)	240 Participants	234 Participants	257 Participants	240 Participants
Change From Baseline to Week 26 in Eye Examination Category Right Eye Ophthalmoscopy - Abnormal NCS (Baseline)	64 Participants	54 Participants	56 Participants	53 Participants
Change From Baseline to Week 26 in Eye Examination Category Right Eye Ophthalmoscopy - Abnormal CS (Baseline)	57 Participants	69 Participants	48 Participants	65 Participants

SECONDARY outcome

Timeframe: From baseline to week 31

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

Number of participants with treatment-emergent severe or blood glucose (BG) confirmed symptomatic hypoglycaemic episodes during exposure to trial product is presented. Severe: requiring assistance from another person for recovery. 'BG-confirmed': hypoglycaemic episode with a plasma glucose value < 3.1 mmol/L (56 mg/dL); The outcome data was evaluated based on the on-treatment observation period: from date of first dose of trial product following randomization up to the first date of any of the following: follow-up visit, premature follow-up visit, last date on trial product plus 38 days or the end of the in-trial observation period.

Outcome measures

Measure	Oral Semaglutide 3 mg n=361 Participants Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=358 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=361 Participants Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=358 Participants Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Number of Participants With Treatment-emergent Severe or Blood Glucose Confirmed Symptomatic Hypoglycaemic Episodes During Exposure to Trial Product	2 Participants	2 Participants	2 Participants	1 Participants

Adverse Events

Oral Semaglutide 3 mg

Serious events: 16 serious events

Other events: 109 other events

Deaths: 2 deaths

Oral Semaglutide 7 mg

Serious events: 11 serious events

Other events: 117 other events

Deaths: 2 deaths

Oral Semaglutide 14 mg

Serious events: 11 serious events

Other events: 144 other events

Deaths: 1 deaths

Sitagliptin 100 mg

Serious events: 15 serious events

Other events: 65 other events

Deaths: 0 deaths

Serious adverse events

Measure	Oral Semaglutide 3 mg n=361 participants at risk Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=358 participants at risk Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=361 participants at risk Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=358 participants at risk Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Cardiac disorders Acute coronary syndrome	0.28% 1/361 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Cardiac disorders Acute myocardial infarction	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.28% 1/358 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Infections and infestations Anal abscess	0.28% 1/361 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
General disorders Asthenia	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.28% 1/358 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Infections and infestations COVID-19	0.55% 2/361 • Number of events 2 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.28% 1/361 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Infections and infestations COVID-19 pneumonia	0.28% 1/361 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.28% 1/358 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.56% 2/358 • Number of events 2 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Renal and urinary disorders Calculus urinary	0.28% 1/361 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Cardiac disorders Cardiac failure	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.28% 1/361 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Cardiac disorders Cardiac failure congestive	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.28% 1/361 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Eye disorders Cataract	0.28% 1/361 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.28% 1/361 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Nervous system disorders Cerebral infarction	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.55% 2/361 • Number of events 2 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Nervous system disorders Cerebrovascular insufficiency	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.28% 1/358 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Reproductive system and breast disorders Cervical dysplasia	0.28% 1/361 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
General disorders Chest pain	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.28% 1/358 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.28% 1/361 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Hepatobiliary disorders Cholecystitis acute	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.28% 1/361 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Hepatobiliary disorders Cholelithiasis	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.28% 1/361 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Gastrointestinal disorders Chronic gastritis	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.28% 1/361 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon adenoma	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.28% 1/358 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Cardiac disorders Coronary artery disease	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.28% 1/358 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.56% 2/358 • Number of events 2 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Infections and infestations Dacryocystitis	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.28% 1/358 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Eye disorders Dacryostenosis acquired	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.28% 1/358 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Nervous system disorders Dementia	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.28% 1/358 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Metabolism and nutrition disorders Diabetic ketoacidosis	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.28% 1/358 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Eye disorders Diabetic retinopathy	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.28% 1/358 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Injury, poisoning and procedural complications Facial bones fracture	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.28% 1/358 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Surgical and medical procedures Fracture treatment	0.28% 1/361 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Hepatobiliary disorders Hepatic function abnormal	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.28% 1/358 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Hepatobiliary disorders Hepatic steatosis	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.28% 1/358 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Injury, poisoning and procedural complications Humerus fracture	0.28% 1/361 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Vascular disorders Hypertension	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.28% 1/358 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Infections and infestations Infected skin ulcer	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.28% 1/361 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Gastrointestinal disorders Inguinal hernia	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.28% 1/358 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.28% 1/361 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Musculoskeletal and connective tissue disorders Intervertebral disc protrusion	0.28% 1/361 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Nervous system disorders Ischaemic stroke	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.28% 1/358 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.28% 1/361 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.28% 1/358 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Infections and infestations Keratitis viral	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.28% 1/358 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Infections and infestations Lacrimal gland abscess	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.28% 1/358 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung adenocarcinoma	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.28% 1/361 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Eye disorders Macular fibrosis	0.28% 1/361 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Nervous system disorders Neuralgia	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.28% 1/358 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Musculoskeletal and connective tissue disorders Osteoporosis	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.28% 1/361 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Infections and infestations Pneumonia	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.28% 1/361 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.28% 1/358 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
General disorders Pyrexia	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.28% 1/358 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Injury, poisoning and procedural complications Spinal compression fracture	0.28% 1/361 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Injury, poisoning and procedural complications Stab wound	0.28% 1/361 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Ear and labyrinth disorders Sudden hearing loss	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.28% 1/361 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Injury, poisoning and procedural complications Ulna fracture	0.28% 1/361 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Gastrointestinal disorders Umbilical hernia	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.28% 1/358 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Infections and infestations Upper respiratory tract infection	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.28% 1/358 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Renal and urinary disorders Ureterolithiasis	0.28% 1/361 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.56% 2/358 • Number of events 2 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Skin and subcutaneous tissue disorders Urticaria	0.28% 1/361 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Nervous system disorders Vertebrobasilar insufficiency	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.28% 1/358 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/361 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.00% 0/358 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.

Other adverse events

Measure	Oral Semaglutide 3 mg n=361 participants at risk Participants received semaglutide 3 mg tablet and placebo tablet matched to sitagliptin orally once daily for 26 weeks.	Oral Semaglutide 7 mg n=358 participants at risk Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4 and 7 mg from week 5 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Oral Semaglutide 14 mg n=361 participants at risk Participants received oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 1 to week 4, 7 mg from week 5 to week 8 and 14 mg from week 9 to week 26. Participants also received placebo matched to sitagliptin 100 mg for 26 weeks.	Sitagliptin 100 mg n=358 participants at risk Participants received oral sitagliptin 100 mg tablet and placebo tablet matched to oral semaglutide orally once daily for 26 weeks.
Metabolism and nutrition disorders Decreased appetite	6.1% 22/361 • Number of events 22 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	8.4% 30/358 • Number of events 30 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	9.4% 34/361 • Number of events 39 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	1.4% 5/358 • Number of events 5 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Gastrointestinal disorders Diarrhoea	8.3% 30/361 • Number of events 31 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	8.9% 32/358 • Number of events 40 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	13.3% 48/361 • Number of events 57 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	4.5% 16/358 • Number of events 17 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Investigations Lipase increased	4.2% 15/361 • Number of events 15 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	4.7% 17/358 • Number of events 22 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	5.8% 21/361 • Number of events 23 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	3.4% 12/358 • Number of events 16 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Gastrointestinal disorders Nausea	10.0% 36/361 • Number of events 38 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	10.9% 39/358 • Number of events 42 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	12.2% 44/361 • Number of events 50 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	3.9% 14/358 • Number of events 15 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Infections and infestations Upper respiratory tract infection	7.2% 26/361 • Number of events 27 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	7.0% 25/358 • Number of events 29 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	8.6% 31/361 • Number of events 35 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	7.8% 28/358 • Number of events 35 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.
Gastrointestinal disorders Vomiting	4.4% 16/361 • Number of events 17 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	5.0% 18/358 • Number of events 30 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	8.0% 29/361 • Number of events 38 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	0.28% 1/358 • Number of events 1 • From baseline to week 31 AEs with onset during the on-treatment period correspond to TEAEs. On-treatment observation period represented the time period where participants were considered treated with the trial product following randomization. Results are based on the SAS which included all participants exposed to at least one dose of trial product.

Additional Information

Clinical Reporting Anchor and Disclosure (2834)

Novo Nordisk A/S

Phone: (+1) 866-867-7178

Email: clinicaltrials@novonordisk.com

Results disclosure agreements

• Principal investigator is a sponsor employee At the end of the trial, one or more scientific publications may be prepared collaboratively by the investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for up to 60 days to protect intellectual property.
• Publication restrictions are in place

Restriction type: OTHER