Trial Outcomes & Findings for A Research Study Comparing a New Medicine Oral Semaglutide to Placebo in People With Type 2 Diabetes (NCT NCT04109547)

Last Updated: 2024-09-19

Results Overview

Change from baseline (week 0) in HbA1c 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 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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

521 participants

Primary outcome timeframe

Baseline (Week 0), Week 26

Results posted on

2024-09-19

Participant Flow

The trial was conducted at 52 sites in 3 countries and Region China (China mainland and Taiwan) as follows: China mainland (37 sites), Taiwan (3 sites); Hungary (4 sites), Serbia (2 sites) and Ukraine (6 sites).

Total of 521 participants with type 2 diabetes mellitus treated with diet and exercise only were randomized 1:1:1:1 to receive once-daily blinded treatment for 26 weeks with oral semaglutide 3, 7 or 14 milligrams (mg), or with placebo. The trial included a 4-week run-in period, a treatment period of 26 weeks and a 5-week follow-up period.

Participant milestones

Participant milestones
Measure	Oral Semaglutide 3 mg Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	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 4 to week 26.	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 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Overall Study STARTED	130	130	130	131
Overall Study Treated	130	130	129	131
Overall Study Full Analysis Set	130	130	130	131
Overall Study Safety Analysis Set	130	130	129	131
Overall Study COMPLETED	126	126	124	124
Overall Study NOT COMPLETED	4	4	6	7

Reasons for withdrawal

Reasons for withdrawal
Measure	Oral Semaglutide 3 mg Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	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 4 to week 26.	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 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Overall Study Withdrawal by Subject	3	2	6	6
Overall Study Lost to Follow-up	0	0	0	1
Overall Study Physician Decision	1	2	0	0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Oral Semaglutide 3 mg n=130 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=130 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 4 to week 26.	Oral Semaglutide 14 mg n=130 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=131 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.	Total n=521 Participants Total of all reporting groups
Age, Continuous	54 Years STANDARD_DEVIATION 11 • n=5 Participants	52 Years STANDARD_DEVIATION 11 • n=7 Participants	53 Years STANDARD_DEVIATION 10 • n=5 Participants	51 Years STANDARD_DEVIATION 11 • n=4 Participants	52 Years STANDARD_DEVIATION 11 • n=21 Participants
Sex: Female, Male Female	58 Participants n=5 Participants	41 Participants n=7 Participants	47 Participants n=5 Participants	43 Participants n=4 Participants	189 Participants n=21 Participants
Sex: Female, Male Male	72 Participants n=5 Participants	89 Participants n=7 Participants	83 Participants n=5 Participants	88 Participants n=4 Participants	332 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	130 Participants n=5 Participants	130 Participants n=7 Participants	129 Participants n=5 Participants	131 Participants n=4 Participants	520 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 Race · American Indian or Alaska Native	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants
Race/Ethnicity, Customized Race · Asian	97 Participants n=5 Participants	97 Participants n=7 Participants	97 Participants n=5 Participants	98 Participants n=4 Participants	389 Participants n=21 Participants
Race/Ethnicity, Customized Race · White	33 Participants n=5 Participants	32 Participants n=7 Participants	33 Participants n=5 Participants	33 Participants n=4 Participants	131 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline (Week 0), Week 26

Population: Full analysis set included all randomized participants. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 3 mg n=114 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=117 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 4 to week 26.	Oral Semaglutide 14 mg n=116 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=106 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Change From Baseline in Glycosylated Haemoglobin (HbA1c)	-1.1 Percentage of HbA1c Standard Deviation 0.7	-1.5 Percentage of HbA1c Standard Deviation 0.8	-1.6 Percentage of HbA1c Standard Deviation 1.0	-0.2 Percentage of HbA1c Standard Deviation 0.9

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 26

Population: Full analysis set included all randomized participants. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Change from baseline (week 0) in body weight 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 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

Outcome measures
Measure	Oral Semaglutide 3 mg n=115 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=119 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 4 to week 26.	Oral Semaglutide 14 mg n=116 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=106 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Change From Baseline in Body Weight (Kilograms [kg])	-1.1 Kg Standard Deviation 3.3	-2.2 Kg Standard Deviation 3.4	-3.1 Kg Standard Deviation 3.7	-1.1 Kg Standard Deviation 2.7

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 26

Population: Full analysis set included all randomized participants. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Change from baseline (week 0) in FPG 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 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

Outcome measures
Measure	Oral Semaglutide 3 mg n=114 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=118 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 4 to week 26.	Oral Semaglutide 14 mg n=116 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=104 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Change From Baseline in Fasting Plasma Glucose (FPG)	-19.07 milligrams per deciliter (mg/dL) Standard Deviation 32.44	-32.28 milligrams per deciliter (mg/dL) Standard Deviation 27.95	-32.50 milligrams per deciliter (mg/dL) Standard Deviation 24.91	0.00 milligrams per deciliter (mg/dL) Standard Deviation 27.49

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 26

Population: Full analysis set included all randomized participants. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Change from baseline (week 0) 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 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

Outcome measures
Measure	Oral Semaglutide 3 mg n=110 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=117 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 4 to week 26.	Oral Semaglutide 14 mg n=115 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=104 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Change From Baseline in Fasting 7-point Self-measured Plasma Glucose (SMPG) Profile: Mean 7-point Profile	-29.4 mg/dL Standard Deviation 29.3	-43.0 mg/dL Standard Deviation 36.1	-44.5 mg/dL Standard Deviation 36.9	-10.3 mg/dL Standard Deviation 37.5

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 26

Population: Full analysis set included all randomized participants. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Change from baseline (week 0) in fasting 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 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

Outcome measures
Measure	Oral Semaglutide 3 mg n=112 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=117 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 4 to week 26.	Oral Semaglutide 14 mg n=115 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=104 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Change From Baseline in Fasting 7-point Self-measured Plasma Glucose Profile: Mean Postprandial Increment (Over All Meals)	-14.5 mg/dL Standard Deviation 34.2	-20.0 mg/dL Standard Deviation 39.9	-27.9 mg/dL Standard Deviation 40.6	-6.7 mg/dL Standard Deviation 35.6

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 26

Population: Full analysis set included all randomized participants. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Change from baseline (week 0) in body weight (measured in kg) 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 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

Outcome measures
Measure	Oral Semaglutide 3 mg n=115 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=119 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 4 to week 26.	Oral Semaglutide 14 mg n=116 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=106 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Change From Baseline in Body Weight (Percentage [%])	-1 Percentage change Standard Deviation 4	-3 Percentage change Standard Deviation 4	-4 Percentage change Standard Deviation 5	-1 Percentage change Standard Deviation 3

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 26

Population: Full analysis set included all randomized participants. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Change from baseline (week 0) in BMI 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 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

Outcome measures
Measure	Oral Semaglutide 3 mg n=115 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=119 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 4 to week 26.	Oral Semaglutide 14 mg n=116 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=106 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Change From Baseline in Body Mass Index (BMI)	-0.4 kilograms per square meter (kg/m^2) Standard Deviation 1.2	-0.8 kilograms per square meter (kg/m^2) Standard Deviation 1.2	-1.1 kilograms per square meter (kg/m^2) Standard Deviation 1.3	-0.4 kilograms per square meter (kg/m^2) Standard Deviation 0.9

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 26

Population: Full analysis set included all randomized participants. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Change from baseline (week 0) in waist circumference 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 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

Outcome measures
Measure	Oral Semaglutide 3 mg n=115 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=119 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 4 to week 26.	Oral Semaglutide 14 mg n=116 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=105 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Change From Baseline in Waist Circumference	-2.1 centimetres (cm) Standard Deviation 4.5	-2.2 centimetres (cm) Standard Deviation 4.8	-2.8 centimetres (cm) Standard Deviation 4.4	-1.4 centimetres (cm) Standard Deviation 3.3

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 26

Population: Full analysis set included all randomized participants. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Change from baseline (week 0) in total cholesterol (measured in mg/dL) 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

Outcome measures
Measure	Oral Semaglutide 3 mg n=115 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=119 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 4 to week 26.	Oral Semaglutide 14 mg n=114 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=104 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Change From Baseline in Fasting Lipid Profile: Total Cholesterol (Ratio to Baseline)	0.99 Ratio of total cholesterol Geometric Coefficient of Variation 14.75	0.98 Ratio of total cholesterol Geometric Coefficient of Variation 16.62	0.94 Ratio of total cholesterol Geometric Coefficient of Variation 19.92	1.00 Ratio of total cholesterol Geometric Coefficient of Variation 14.45

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 26

Population: Full analysis set included all randomized participants. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Change from baseline (week 0) in LDL cholesterol (measured in mg/dL) 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

Outcome measures
Measure	Oral Semaglutide 3 mg n=115 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=119 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 4 to week 26.	Oral Semaglutide 14 mg n=114 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=102 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Change From Baseline in Fasting Lipid Profile: Low-density Lipoprotein (LDL) Cholesterol (Ratio to Baseline)	1.00 Ratio of LDL cholesterol Geometric Coefficient of Variation 29.65	1.00 Ratio of LDL cholesterol Geometric Coefficient of Variation 28.35	0.94 Ratio of LDL cholesterol Geometric Coefficient of Variation 31.12	1.00 Ratio of LDL cholesterol Geometric Coefficient of Variation 25.32

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 26

Population: Full analysis set included all randomized participants. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Change from baseline (week 0) in HDL cholesterol (measured in mg/dL) 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

Outcome measures
Measure	Oral Semaglutide 3 mg n=115 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=119 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 4 to week 26.	Oral Semaglutide 14 mg n=114 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=102 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Change From Baseline in Fasting Lipid Profile: High-density Lipoprotein (HDL) Cholesterol (Ratio to Baseline)	1.03 Ratio of HDL cholesterol Geometric Coefficient of Variation 15.78	1.02 Ratio of HDL cholesterol Geometric Coefficient of Variation 15.41	1.02 Ratio of HDL cholesterol Geometric Coefficient of Variation 17.72	1.04 Ratio of HDL cholesterol Geometric Coefficient of Variation 14.61

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 26

Population: Full analysis set included all randomized participants. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Change from baseline (week 0) in triglycerides (measured in mg/dL) 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

Outcome measures
Measure	Oral Semaglutide 3 mg n=114 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=119 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 4 to week 26.	Oral Semaglutide 14 mg n=114 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=102 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Change From Baseline in Fasting Lipid Profile: Triglycerides (Ratio to Baseline)	0.96 Ratio of triglycerides Geometric Coefficient of Variation 45.32	0.90 Ratio of triglycerides Geometric Coefficient of Variation 45.56	0.87 Ratio of triglycerides Geometric Coefficient of Variation 51.82	0.93 Ratio of triglycerides Geometric Coefficient of Variation 49.08

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 26

Population: Full analysis set included all randomized participants. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

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). Change form baseline in each domain, physical component summary score and mental component summary score at week 26 is presented. A positive change score indicates an improvement since 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

Outcome measures
Measure	Oral Semaglutide 3 mg n=115 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=119 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 4 to week 26.	Oral Semaglutide 14 mg n=115 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=106 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Change From Baseline in Short Form-36 Version 2 (SF-36v2) (Acute Version) Health Survey Physical functioning	0.25 Units on a score Standard Deviation 4.83	0.97 Units on a score Standard Deviation 5.16	0.34 Units on a score Standard Deviation 4.24	0.87 Units on a score Standard Deviation 4.98
Change From Baseline in Short Form-36 Version 2 (SF-36v2) (Acute Version) Health Survey Role physical	0.34 Units on a score Standard Deviation 5.70	0.43 Units on a score Standard Deviation 5.83	-0.00 Units on a score Standard Deviation 5.02	0.33 Units on a score Standard Deviation 7.50
Change From Baseline in Short Form-36 Version 2 (SF-36v2) (Acute Version) Health Survey Bodily pain	0.11 Units on a score Standard Deviation 8.72	-0.86 Units on a score Standard Deviation 8.19	-0.34 Units on a score Standard Deviation 6.56	0.49 Units on a score Standard Deviation 8.40
Change From Baseline in Short Form-36 Version 2 (SF-36v2) (Acute Version) Health Survey General health	2.01 Units on a score Standard Deviation 7.14	2.51 Units on a score Standard Deviation 7.52	1.32 Units on a score Standard Deviation 8.61	1.17 Units on a score Standard Deviation 5.91
Change From Baseline in Short Form-36 Version 2 (SF-36v2) (Acute Version) Health Survey Vitality	1.23 Units on a score Standard Deviation 7.62	-0.23 Units on a score Standard Deviation 6.96	0.54 Units on a score Standard Deviation 8.02	0.49 Units on a score Standard Deviation 6.35
Change From Baseline in Short Form-36 Version 2 (SF-36v2) (Acute Version) Health Survey Social functioning	0.22 Units on a score Standard Deviation 6.26	0.25 Units on a score Standard Deviation 7.22	-0.60 Units on a score Standard Deviation 6.18	0.98 Units on a score Standard Deviation 7.04
Change From Baseline in Short Form-36 Version 2 (SF-36v2) (Acute Version) Health Survey Role emotional	0.46 Units on a score Standard Deviation 6.94	0.58 Units on a score Standard Deviation 8.34	0.33 Units on a score Standard Deviation 7.03	-0.04 Units on a score Standard Deviation 9.03
Change From Baseline in Short Form-36 Version 2 (SF-36v2) (Acute Version) Health Survey Mental health	0.22 Units on a score Standard Deviation 7.59	-0.38 Units on a score Standard Deviation 7.96	-0.30 Units on a score Standard Deviation 7.78	0.05 Units on a score Standard Deviation 6.99
Change From Baseline in Short Form-36 Version 2 (SF-36v2) (Acute Version) Health Survey Physical component score	0.66 Units on a score Standard Deviation 5.21	0.88 Units on a score Standard Deviation 4.98	0.39 Units on a score Standard Deviation 4.60	0.94 Units on a score Standard Deviation 4.71
Change From Baseline in Short Form-36 Version 2 (SF-36v2) (Acute Version) Health Survey Mental component score	0.51 Units on a score Standard Deviation 6.86	-0.15 Units on a score Standard Deviation 7.65	-0.10 Units on a score Standard Deviation 6.44	0.08 Units on a score Standard Deviation 6.88

SECONDARY outcome

Timeframe: Week 26

Population: Full analysis set 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 % (53 mmol/mol) (ADA target) 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 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

Outcome measures
Measure	Oral Semaglutide 3 mg n=114 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=117 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 4 to week 26.	Oral Semaglutide 14 mg n=116 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=106 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Number of Participants Who Achieved HbA1c Less Than (<) 7.0 % (53 Millimoles Per Mole [mmol/Mol]) (American Diabetes Association (ADA) Target) (Yes/no) Yes	75 Participants	100 Participants	92 Participants	27 Participants
Number of Participants Who Achieved HbA1c Less Than (<) 7.0 % (53 Millimoles Per Mole [mmol/Mol]) (American Diabetes Association (ADA) Target) (Yes/no) No	39 Participants	17 Participants	24 Participants	79 Participants

SECONDARY outcome

Timeframe: Week 26

Population: Full analysis set included all randomized participants. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Number of participants who achieved HbA1c \<= 6.5 percent (48 mmol/mol) (AACE target) 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 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

Outcome measures
Measure	Oral Semaglutide 3 mg n=114 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=117 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 4 to week 26.	Oral Semaglutide 14 mg n=116 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=106 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Number of Participants Who Achieved HbA1c Less Than or Equal to (<=) 6.5 Percent (48 mmol/Mol) (American Association of Clinical Endocrinologists (AACE) Target) (Yes/no) Yes	53 Participants	76 Participants	76 Participants	12 Participants
Number of Participants Who Achieved HbA1c Less Than or Equal to (<=) 6.5 Percent (48 mmol/Mol) (American Association of Clinical Endocrinologists (AACE) Target) (Yes/no) No	61 Participants	41 Participants	40 Participants	94 Participants

SECONDARY outcome

Timeframe: Week 26

Population: Full analysis set included all randomized participants. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Number of participants who achieved HbA1c reduction \>= 1 percent (10.9 mmol/mol) 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 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

Outcome measures
Measure	Oral Semaglutide 3 mg n=114 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=117 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 4 to week 26.	Oral Semaglutide 14 mg n=116 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=106 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Number of Participants Who Achieved HbA1c Reduction Greater Than or Equal to (>=) 1 Percent (10.9 mmol/Mol) (Yes/no) Yes	67 Participants	89 Participants	87 Participants	19 Participants
Number of Participants Who Achieved HbA1c Reduction Greater Than or Equal to (>=) 1 Percent (10.9 mmol/Mol) (Yes/no) No	47 Participants	28 Participants	29 Participants	87 Participants

SECONDARY outcome

Timeframe: Week 26

Population: Full analysis set 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 \>= 3 percent (yes/no) 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 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

Outcome measures
Measure	Oral Semaglutide 3 mg n=114 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=117 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 4 to week 26.	Oral Semaglutide 14 mg n=116 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=106 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Number of Participants Who Achieved Body Weight Loss >= 3 Percent (Yes/no) Yes	33 Participants	49 Participants	62 Participants	28 Participants
Number of Participants Who Achieved Body Weight Loss >= 3 Percent (Yes/no) No	81 Participants	68 Participants	54 Participants	78 Participants

SECONDARY outcome

Timeframe: Week 26

Population: Full analysis set 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 \>= 5 percent (yes/no) 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 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

Outcome measures
Measure	Oral Semaglutide 3 mg n=115 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=119 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 4 to week 26.	Oral Semaglutide 14 mg n=116 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=106 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Number of Participants Who Achieved Body Weight Loss >= 5 Percent (Yes/no) Yes	17 Participants	29 Participants	43 Participants	11 Participants
Number of Participants Who Achieved Body Weight Loss >= 5 Percent (Yes/no) No	98 Participants	90 Participants	73 Participants	95 Participants

SECONDARY outcome

Timeframe: Week 26

Population: Full analysis set 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 \>= 10 percent (yes/no) 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 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

Outcome measures
Measure	Oral Semaglutide 3 mg n=115 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=119 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 4 to week 26.	Oral Semaglutide 14 mg n=116 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=106 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Number of Participants Who Achieved Body Weight Loss >= 10 Percent (Yes/no) Yes	5 Participants	7 Participants	12 Participants	0 Participants
Number of Participants Who Achieved Body Weight Loss >= 10 Percent (Yes/no) No	110 Participants	112 Participants	104 Participants	106 Participants

SECONDARY outcome

Timeframe: Week 26

Population: Full analysis set 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 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

Outcome measures
Measure	Oral Semaglutide 3 mg n=114 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=117 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 4 to week 26.	Oral Semaglutide 14 mg n=116 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=106 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Number of Participants Who Achieved HbA1c < 7.0 Percent (53 mmol/Mol) Without Hypoglycaemia (Treatment-emergent Severe or Blood Glucose [BG] Confirmed Symptomatic Hypoglycaemic Episodes) and no Body Weight Gain (Yes/no) Yes	54 Participants	80 Participants	84 Participants	19 Participants
Number of Participants Who Achieved HbA1c < 7.0 Percent (53 mmol/Mol) Without Hypoglycaemia (Treatment-emergent Severe or Blood Glucose [BG] Confirmed Symptomatic Hypoglycaemic Episodes) and no Body Weight Gain (Yes/no) No	60 Participants	37 Participants	32 Participants	87 Participants

SECONDARY outcome

Timeframe: Week 26

Population: Full analysis set included all randomized participants. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Number of participants who achieved HbA1c reduction \>= 1% (10.9 mmol/mol) and body weight loss \>= 3% (yes/no) 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 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

Outcome measures
Measure	Oral Semaglutide 3 mg n=114 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=117 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 4 to week 26.	Oral Semaglutide 14 mg n=116 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=106 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Number of Participants Who Achieved HbA1c Reduction >= 1% (10.9 mmol/Mol) and Body Weight Loss >= 3 Percent (Yes/no) Yes	26 Participants	43 Participants	53 Participants	10 Participants
Number of Participants Who Achieved HbA1c Reduction >= 1% (10.9 mmol/Mol) and Body Weight Loss >= 3 Percent (Yes/no) No	88 Participants	74 Participants	63 Participants	96 Participants

SECONDARY outcome

Timeframe: From baseline (Week 0) to Week 26

Population: Full analysis set included all randomized participants. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Rescue medication was defined as any new anti-diabetic medication used as add-on to trial product and used for more than 21 days with the initiation at or after randomization 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 randomization 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 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

Outcome measures
Measure	Oral Semaglutide 3 mg n=6 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=3 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 4 to week 26.	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 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=15 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Time From First Dose to Initiation of Rescue Medication	NA Days Median days to event could not be calculated because less than 50% of participants experienced the event. Hence the days are reported as Not available (NA).	NA Days Median days to event could not be calculated because less than 50% of participants experienced the event. Hence the days are reported as NA.	—	NA Days Median days to event could not be calculated because less than 50% of participants experienced the event. Hence the days are reported as NA.

SECONDARY outcome

Timeframe: Week 26: post dose any time

Population: Full analysis set included all randomized participants. Overall Number of Participants Analyzed = participants with available data for this outcome measure.

Semaglutide plasma concentrations 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 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

Outcome measures
Measure	Oral Semaglutide 3 mg n=86 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=88 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 4 to week 26.	Oral Semaglutide 14 mg n=79 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Semaglutide Plasma Concentrations	4.36 nanomoles per liter (nmol/L) Geometric Coefficient of Variation 103.74	11.22 nanomoles per liter (nmol/L) Geometric Coefficient of Variation 106.34	17.71 nanomoles per liter (nmol/L) Geometric Coefficient of Variation 232.82	—

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 26

Change from baseline (week 0) in haematocrit (measured in %) 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 last date on trial product plus 3 days.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 3 mg n=120 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=117 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 4 to week 26.	Oral Semaglutide 14 mg n=116 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=118 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Change From Baseline in Haematology - Haematocrit (Ratio to Baseline)	1.00 Ratio of haematocrit Geometric Coefficient of Variation 7.14	1.00 Ratio of haematocrit Geometric Coefficient of Variation 8.10	1.00 Ratio of haematocrit Geometric Coefficient of Variation 6.15	1.00 Ratio of haematocrit Geometric Coefficient of Variation 14.42

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 26

Change from baseline (week 0) in haemoglobin (measured in millimoles per liter \[mmol/L\]) 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 last date on trial product plus 3 days.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 3 mg n=120 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=117 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 4 to week 26.	Oral Semaglutide 14 mg n=116 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=118 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Change From Baseline in Haematology - Haemoglobin (Ratio to Baseline)	1.01 Ratio of haemoglobin Geometric Coefficient of Variation 6.00	1.00 Ratio of haemoglobin Geometric Coefficient of Variation 6.82	1.00 Ratio of haemoglobin Geometric Coefficient of Variation 6.17	1.00 Ratio of haemoglobin Geometric Coefficient of Variation 7.50

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 26

Change from baseline (week 0) in leucocytes (measured in 10\^9 per liter \[10\^9/L\]) 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 last date on trial product plus 3 days.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 3 mg n=120 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=117 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 4 to week 26.	Oral Semaglutide 14 mg n=116 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=118 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Change From Baseline in Haematology - Leucocytes (Ratio to Baseline)	1.03 Ratio of leucocytes Geometric Coefficient of Variation 18.79	1.01 Ratio of leucocytes Geometric Coefficient of Variation 22.23	1.04 Ratio of leucocytes Geometric Coefficient of Variation 22.60	1.03 Ratio of leucocytes Geometric Coefficient of Variation 20.80

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 26

Change from baseline (week 0) in thrombocytes (measured in 10\^9/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 last date on trial product plus 3 days.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 3 mg n=118 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=115 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 4 to week 26.	Oral Semaglutide 14 mg n=114 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=118 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Change From Baseline in Haematology - Thrombocytes (Ratio to Baseline)	1.03 Ratio of thrombocytes Geometric Coefficient of Variation 23.24	1.01 Ratio of thrombocytes Geometric Coefficient of Variation 17.69	1.04 Ratio of thrombocytes Geometric Coefficient of Variation 17.55	1.02 Ratio of thrombocytes Geometric Coefficient of Variation 19.98

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 26

Change from baseline (week 0) in basophils, eosinophils, lymphocytes, monocytes and neutrophils at week 26 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 last date on trial product plus 3 days.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 3 mg n=119 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=117 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 4 to week 26.	Oral Semaglutide 14 mg n=116 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=118 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Change From Baseline in Haematology - Basophils, Eosinophils, Lymphocytes, Monocytes and Neutrophils Basophils	0.00 10^9 cells per liters (10^9 cells/L) Standard Deviation 0.06	-0.01 10^9 cells per liters (10^9 cells/L) Standard Deviation 0.06	-0.01 10^9 cells per liters (10^9 cells/L) Standard Deviation 0.06	-0.01 10^9 cells per liters (10^9 cells/L) Standard Deviation 0.07
Change From Baseline in Haematology - Basophils, Eosinophils, Lymphocytes, Monocytes and Neutrophils Eosinophils	0.01 10^9 cells per liters (10^9 cells/L) Standard Deviation 0.10	0.02 10^9 cells per liters (10^9 cells/L) Standard Deviation 0.10	0.02 10^9 cells per liters (10^9 cells/L) Standard Deviation 0.12	0.01 10^9 cells per liters (10^9 cells/L) Standard Deviation 0.08
Change From Baseline in Haematology - Basophils, Eosinophils, Lymphocytes, Monocytes and Neutrophils Lymphocytes	0.05 10^9 cells per liters (10^9 cells/L) Standard Deviation 0.43	-0.03 10^9 cells per liters (10^9 cells/L) Standard Deviation 0.49	-0.09 10^9 cells per liters (10^9 cells/L) Standard Deviation 0.49	0.02 10^9 cells per liters (10^9 cells/L) Standard Deviation 0.46
Change From Baseline in Haematology - Basophils, Eosinophils, Lymphocytes, Monocytes and Neutrophils Monocytes	0.01 10^9 cells per liters (10^9 cells/L) Standard Deviation 0.12	-0.00 10^9 cells per liters (10^9 cells/L) Standard Deviation 0.16	0.01 10^9 cells per liters (10^9 cells/L) Standard Deviation 0.16	0.01 10^9 cells per liters (10^9 cells/L) Standard Deviation 0.15
Change From Baseline in Haematology - Basophils, Eosinophils, Lymphocytes, Monocytes and Neutrophils Neutrophils	0.18 10^9 cells per liters (10^9 cells/L) Standard Deviation 0.98	0.06 10^9 cells per liters (10^9 cells/L) Standard Deviation 1.44	0.28 10^9 cells per liters (10^9 cells/L) Standard Deviation 1.19	0.21 10^9 cells per liters (10^9 cells/L) Standard Deviation 1.14

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 26

Change from baseline (week 0) 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 last date on trial product plus 3 days.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 3 mg n=121 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=122 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 4 to week 26.	Oral Semaglutide 14 mg n=114 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=119 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Change From Baseline in Biochemistry - Urea (Ratio to Baseline)	1.02 Ratio of urea Geometric Coefficient of Variation 21.23	1.00 Ratio of urea Geometric Coefficient of Variation 24.90	1.02 Ratio of urea Geometric Coefficient of Variation 23.12	1.07 Ratio of urea Geometric Coefficient of Variation 23.97

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 26

Change from baseline (week 0) in creatinine (measured in mg/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 last date on trial product plus 3 days.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 3 mg n=121 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=122 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 4 to week 26.	Oral Semaglutide 14 mg n=116 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=119 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Change From Baseline in Biochemistry - Creatinine (Ratio to Baseline)	1.03 Ratio of creatinine Geometric Coefficient of Variation 10.39	1.02 Ratio of creatinine Geometric Coefficient of Variation 13.25	1.03 Ratio of creatinine Geometric Coefficient of Variation 11.50	0.99 Ratio of creatinine Geometric Coefficient of Variation 11.49

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 26

Change from baseline (week 0) in alanine aminotransferase (measured in units per liter \[U/L\]) 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 last date on trial product plus 3 days.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 3 mg n=121 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=122 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 4 to week 26.	Oral Semaglutide 14 mg n=116 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=118 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Change From Baseline in Biochemistry - Alanine Aminotransferase (Ratio to Baseline)	0.88 Ratio of alanine aminotransferase Geometric Coefficient of Variation 44.27	0.89 Ratio of alanine aminotransferase Geometric Coefficient of Variation 45.23	0.85 Ratio of alanine aminotransferase Geometric Coefficient of Variation 47.44	0.88 Ratio of alanine aminotransferase Geometric Coefficient of Variation 42.72

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 26

Change from baseline (week 0) in aspartate aminotransferase (measured in U/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 last date on trial product plus 3 days.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 3 mg n=120 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=120 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 4 to week 26.	Oral Semaglutide 14 mg n=111 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=116 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Change From Baseline in Biochemistry - Aspartate Aminotransferase (Ratio to Baseline)	0.91 Ratio of aspartate aminotransferase Geometric Coefficient of Variation 30.50	0.91 Ratio of aspartate aminotransferase Geometric Coefficient of Variation 34.42	0.90 Ratio of aspartate aminotransferase Geometric Coefficient of Variation 35.09	0.89 Ratio of aspartate aminotransferase Geometric Coefficient of Variation 38.14

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 26

Change from baseline (week 0) in alkaline phosphatase (measured in U/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 last date on trial product plus 3 days.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 3 mg n=121 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=122 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 4 to week 26.	Oral Semaglutide 14 mg n=114 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=119 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Change From Baseline in Biochemistry - Alkaline Phosphatase (Ratio to Baseline)	0.94 Ratio of alkaline phosphatase Geometric Coefficient of Variation 15.14	0.92 Ratio of alkaline phosphatase Geometric Coefficient of Variation 20.54	0.95 Ratio of alkaline phosphatase Geometric Coefficient of Variation 17.83	0.95 Ratio of alkaline phosphatase Geometric Coefficient of Variation 13.83

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 26

Change from baseline (week 0) in total bilirubin (measured in mg/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 last date on trial product plus 3 days.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 3 mg n=121 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=122 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 4 to week 26.	Oral Semaglutide 14 mg n=114 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=117 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Change From Baseline in Biochemistry - Total Bilirubin (Ratio to Baseline)	0.89 Ratio of total bilirubin Geometric Coefficient of Variation 34.97	0.84 Ratio of total bilirubin Geometric Coefficient of Variation 32.62	0.85 Ratio of total bilirubin Geometric Coefficient of Variation 41.55	0.95 Ratio of total bilirubin Geometric Coefficient of Variation 39.68

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 26

Change from baseline (week 0) in amylase (measured in U/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 last date on trial product plus 3 days.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 3 mg n=121 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=122 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 4 to week 26.	Oral Semaglutide 14 mg n=114 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=119 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Change From Baseline in Biochemistry - Amylase (Ratio to Baseline)	1.09 Ratio of amylase Geometric Coefficient of Variation 23.53	1.20 Ratio of amylase Geometric Coefficient of Variation 27.17	1.11 Ratio of amylase Geometric Coefficient of Variation 21.64	1.05 Ratio of amylase Geometric Coefficient of Variation 26.52

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 26

Change from baseline (week 0) in lipase (measured in U/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 last date on trial product plus 3 days.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 3 mg n=121 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=122 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 4 to week 26.	Oral Semaglutide 14 mg n=114 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=119 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Change From Baseline in Biochemistry - Lipase (Ratio to Baseline)	1.24 Ratio of lipase Geometric Coefficient of Variation 43.99	1.60 Ratio of lipase Geometric Coefficient of Variation 55.40	1.35 Ratio of lipase Geometric Coefficient of Variation 51.48	1.05 Ratio of lipase Geometric Coefficient of Variation 32.22

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 26

Change from baseline (week 0) in creatine kinase (measured in U/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 last date on trial product plus 3 days.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 3 mg n=121 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=122 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 4 to week 26.	Oral Semaglutide 14 mg n=114 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=118 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Change From Baseline in Biochemistry - Creatine Kinase (Ratio to Baseline)	1.06 Ratio of creatine kinase Geometric Coefficient of Variation 67.51	0.96 Ratio of creatine kinase Geometric Coefficient of Variation 48.18	1.00 Ratio of creatine kinase Geometric Coefficient of Variation 46.25	0.93 Ratio of creatine kinase Geometric Coefficient of Variation 58.87

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 26

Change from baseline (week 0) in calcium (measured in mg/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 last date on trial product plus 3 days.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 3 mg n=121 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=122 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 4 to week 26.	Oral Semaglutide 14 mg n=114 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=119 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Change From Baseline in Calcium (Ratio to Baseline)	0.98 Ratio of calcium Geometric Coefficient of Variation 6.66	0.97 Ratio of calcium Geometric Coefficient of Variation 4.87	0.98 Ratio of calcium Geometric Coefficient of Variation 4.52	0.97 Ratio of calcium Geometric Coefficient of Variation 3.79

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 26

Change from baseline (week 0) in potassium (measured in milliequivalents per liter \[mEq/L\]) 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 last date on trial product plus 3 days.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 3 mg n=119 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=121 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 4 to week 26.	Oral Semaglutide 14 mg n=114 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=118 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Change From Baseline in Potassium (Ratio to Baseline)	1.02 Ratio of potassium Geometric Coefficient of Variation 9.73	1.01 Ratio of potassium Geometric Coefficient of Variation 8.96	1.00 Ratio of potassium Geometric Coefficient of Variation 9.94	1.01 Ratio of potassium Geometric Coefficient of Variation 9.98

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 26

Change from baseline (week 0) in sodium (measured in mEq/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 last date on trial product plus 3 days.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 3 mg n=119 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=122 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 4 to week 26.	Oral Semaglutide 14 mg n=114 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=118 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Change From Baseline in Sodium (Ratio to Baseline)	1.00 Ratio of sodium Geometric Coefficient of Variation 1.49	1.00 Ratio of sodium Geometric Coefficient of Variation 1.46	1.00 Ratio of sodium Geometric Coefficient of Variation 1.42	1.00 Ratio of sodium Geometric Coefficient of Variation 1.32

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 26

Change from baseline (week 0) in albumin (measured in 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 last date on trial product plus 3 days.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 3 mg n=121 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=122 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 4 to week 26.	Oral Semaglutide 14 mg n=114 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=119 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Change From Baseline in Albumin (Ratio to Baseline)	1.00 Ratio of albumin Geometric Coefficient of Variation 4.07	0.99 Ratio of albumin Geometric Coefficient of Variation 4.73	0.99 Ratio of albumin Geometric Coefficient of Variation 4.41	0.99 Ratio of albumin Geometric Coefficient of Variation 3.95

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 26

Change from baseline (week 0) 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 last date on trial product plus 3 days.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 3 mg n=121 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=119 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 4 to week 26.	Oral Semaglutide 14 mg n=116 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=118 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Change From Baseline in Calcitonin (Ratio to Baseline)	1.01 Ratio of calcitonin Geometric Coefficient of Variation 23.53	1.09 Ratio of calcitonin Geometric Coefficient of Variation 39.69	1.15 Ratio of calcitonin Geometric Coefficient of Variation 42.68	0.98 Ratio of calcitonin Geometric Coefficient of Variation 46.93

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 26

Change from baseline (week 0) in pulse rate at week 26 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 last date on trial product plus 3 days.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 3 mg n=121 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=122 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 4 to week 26.	Oral Semaglutide 14 mg n=116 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=121 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Change From Baseline in Pulse Rate	2 Beats per minute (beats/min) Standard Deviation 9	4 Beats per minute (beats/min) Standard Deviation 9	5 Beats per minute (beats/min) Standard Deviation 9	1 Beats per minute (beats/min) Standard Deviation 9

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 26

Change from baseline (week 0) in systolic blood pressure at week 26 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 last date on trial product plus 3 days.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 3 mg n=121 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=122 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 4 to week 26.	Oral Semaglutide 14 mg n=116 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=121 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Change From Baseline in Systolic Blood Pressure	1 millimeters of mercury (mmHg) Standard Deviation 13	-2 millimeters of mercury (mmHg) Standard Deviation 12	-4 millimeters of mercury (mmHg) Standard Deviation 13	-2 millimeters of mercury (mmHg) Standard Deviation 13

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 26

Change from baseline (week 0) in diastolic blood pressure at week 26 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 last date on trial product plus 3 days.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 3 mg n=121 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=122 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 4 to week 26.	Oral Semaglutide 14 mg n=116 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=121 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Change From Baseline in Diastolic Blood Pressure	0 mmHg Standard Deviation 9	-1 mmHg Standard Deviation 8	-2 mmHg Standard Deviation 9	-2 mmHg Standard Deviation 9

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 26

Population: Safety analysis set 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 (week 0) 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, follow-up prematurely discontinuation visit, last dose of trial product plus 38 days or the end-date for the in-trial observation period.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 3 mg n=121 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=123 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 4 to week 26.	Oral Semaglutide 14 mg n=119 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=121 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Change From Baseline in Electrocardiogram (ECG) Category Normal (week 0) to normal (week 26)	53 Participants	61 Participants	59 Participants	58 Participants
Change From Baseline in Electrocardiogram (ECG) Category Normal (week 0) to abnormal NCS (week 26)	12 Participants	11 Participants	9 Participants	5 Participants
Change From Baseline in Electrocardiogram (ECG) Category Normal (week 0) to abnormal CS (week 26)	1 Participants	3 Participants	1 Participants	3 Participants
Change From Baseline in Electrocardiogram (ECG) Category Abnormal NCS (week 0) to normal (week 26)	9 Participants	11 Participants	19 Participants	12 Participants
Change From Baseline in Electrocardiogram (ECG) Category Abnormal NCS (week 0) to abnormal NCS (week 26)	26 Participants	23 Participants	23 Participants	33 Participants
Change From Baseline in Electrocardiogram (ECG) Category Abnormal NCS (week 0) to abnormal CS (week 26)	2 Participants	0 Participants	1 Participants	0 Participants
Change From Baseline in Electrocardiogram (ECG) Category Abnormal CS (week 0) to normal (week 26)	6 Participants	4 Participants	2 Participants	5 Participants
Change From Baseline in Electrocardiogram (ECG) Category Abnormal CS (week 0) to abnormal NCS (week 26)	1 Participants	1 Participants	1 Participants	1 Participants
Change From Baseline in Electrocardiogram (ECG) Category Abnormal CS (week 0) to abnormal CS (week 26)	11 Participants	9 Participants	4 Participants	4 Participants

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 26

Change from baseline (week 0) in physical examination category at week 26 is presented. The physical examination shift in findings were categorized as normal, abnormal NCS and abnormal CS and 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 last date on trial product plus 3 days.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 3 mg n=121 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=122 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 4 to week 26.	Oral Semaglutide 14 mg n=116 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=121 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Change From Baseline in Physical Examination Category Head, Ears, Eyes, Nose, Throat, Neck - Normal (week 0) to abnormal NCS (week 26)	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Physical Examination Category Head, Ears, Eyes, Nose, Throat, Neck - Normal (week 0) to abnormal CS (week 26)	0 Participants	0 Participants	0 Participants	1 Participants
Change From Baseline in Physical Examination Category Head, Ears, Eyes, Nose, Throat, Neck - Abnormal NCS (week 0) to abnormal CS (week 26)	—	0 Participants	—	0 Participants
Change From Baseline in Physical Examination Category Head, Ears, Eyes, Nose, Throat, Neck - Abnormal NCS (week 0) to normal (week 26)	—	0 Participants	—	1 Participants
Change From Baseline in Physical Examination Category Head, Ears, Eyes, Nose, Throat, Neck - Abnormal NCS (week 0) to abnormal NCS (week 26)	—	1 Participants	—	1 Participants
Change From Baseline in Physical Examination Category Head, Ears, Eyes, Nose, Throat, Neck - Abnormal CS (week 0) to normal (week 26)	—	0 Participants	0 Participants	0 Participants
Change From Baseline in Physical Examination Category Head, Ears, Eyes, Nose, Throat, Neck - Abnormal CS (week 0) to abnormal NCS (week 26)	—	0 Participants	0 Participants	0 Participants
Change From Baseline in Physical Examination Category Head, Ears, Eyes, Nose, Throat, Neck - Abnormal CS (week 0) to abnormal CS (week 26)	—	3 Participants	1 Participants	1 Participants
Change From Baseline in Physical Examination Category Lymph Node Palpation - Normal (week 0) to normal (week 26)	120 Participants	121 Participants	115 Participants	119 Participants
Change From Baseline in Physical Examination Category Lymph Node Palpation - Normal (week 0) to abnormal NCS (week 26)	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Physical Examination Category Lymph Node Palpation - Normal (week 0) to abnormal CS (week 26)	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Physical Examination Category Lymph Node Palpation - Abnormal NCS (week 0) to normal (week 26)	1 Participants	1 Participants	1 Participants	2 Participants
Change From Baseline in Physical Examination Category Lymph Node Palpation - Abnormal NCS (week 0) to abnormal NCS (week 26)	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Physical Examination Category Lymph Node Palpation - Abnormal NCS (week 0) to abnormal CS (week 26)	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Physical Examination Category Musculoskeletal System - Normal (week 0) to normal (week 26)	119 Participants	119 Participants	115 Participants	119 Participants
Change From Baseline in Physical Examination Category Musculoskeletal System - Normal (week 0) to abnormal NCS (week 26)	1 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Physical Examination Category Musculoskeletal System - Normal (week 0) to abnormal CS (week 26)	0 Participants	0 Participants	0 Participants	1 Participants
Change From Baseline in Physical Examination Category Musculoskeletal System - Abnormal NCS (week 0) to normal (week 26)	0 Participants	0 Participants	0 Participants	—
Change From Baseline in Physical Examination Category Musculoskeletal System - Abnormal NCS (week 0) to abnormal CS (week 26)	0 Participants	0 Participants	0 Participants	—
Change From Baseline in Physical Examination Category Musculoskeletal System - Abnormal NCS (week 0) to abnormal NCS (week 26)	1 Participants	1 Participants	1 Participants	—
Change From Baseline in Physical Examination Category Musculoskeletal System - Abnormal CS (week 0) to normal (week 26)	—	1 Participants	—	0 Participants
Change From Baseline in Physical Examination Category Musculoskeletal System - Abnormal CS (week 0) to abnormal NCS (week 26)	—	0 Participants	—	0 Participants
Change From Baseline in Physical Examination Category Musculoskeletal System - Abnormal CS (week 0) to abnormal CS (week 26)	—	1 Participants	—	1 Participants
Change From Baseline in Physical Examination Category Respiratory System - Normal (week 0) to normal (week 26)	121 Participants	122 Participants	116 Participants	121 Participants
Change From Baseline in Physical Examination Category Respiratory System - Normal (week 0) to abnormal NCS (week 26)	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Physical Examination Category Respiratory System - Normal (week 0) to abnormal CS (week 26)	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Physical Examination Category Respiratory System - Abnormal CS (week 0) to abnormal NCS (week 26)	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Physical Examination Category Skin - Normal (week 0) to normal (week 26)	99 Participants	106 Participants	98 Participants	105 Participants
Change From Baseline in Physical Examination Category Skin - Normal (week 0) to abnormal NCS (week 26)	1 Participants	0 Participants	1 Participants	0 Participants
Change From Baseline in Physical Examination Category Skin - Normal (week 0) to abnormal CS (week 26)	1 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Physical Examination Category Skin - Abnormal NCS (week 0) to normal (week 26)	2 Participants	0 Participants	3 Participants	3 Participants
Change From Baseline in Physical Examination Category Skin - Abnormal NCS (week 0) to abnormal NCS (week 26)	11 Participants	7 Participants	11 Participants	9 Participants
Change From Baseline in Physical Examination Category Skin - Abnormal NCS (week 0) to abnormal CS (week 26)	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Physical Examination Category Skin - Abnormal CS (week 0) to normal (week 26)	0 Participants	2 Participants	1 Participants	1 Participants
Change From Baseline in Physical Examination Category Skin - Abnormal CS (week 0) to abnormal NCS (week 26)	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Physical Examination Category Skin - Abnormal CS (week 0) to abnormal CS (week 26)	7 Participants	7 Participants	2 Participants	3 Participants
Change From Baseline in Physical Examination Category Thyroid Gland - Normal (week 0) to normal (week 26)	119 Participants	120 Participants	113 Participants	119 Participants
Change From Baseline in Physical Examination Category Thyroid Gland - Normal (week 0) to abnormal NCS (week 26)	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Physical Examination Category Thyroid Gland - Normal (week 0) to abnormal CS (week 26)	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Physical Examination Category Cardiovascular system - Normal (week 0) to normal (week 26)	113 Participants	118 Participants	115 Participants	115 Participants
Change From Baseline in Physical Examination Category Cardiovascular system - Normal (week 0) to abnormal NCS (week 26)	0 Participants	0 Participants	0 Participants	1 Participants
Change From Baseline in Physical Examination Category Cardiovascular system - Normal (week 0) to abnormal CS (week 26)	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Physical Examination Category Cardiovascular system - Abnormal NCS (week 0) to normal (week 26)	3 Participants	2 Participants	0 Participants	0 Participants
Change From Baseline in Physical Examination Category Cardiovascular system - Abnormal NCS (week 0) to abnormal NCS (week 26)	5 Participants	2 Participants	1 Participants	4 Participants
Change From Baseline in Physical Examination Category Cardiovascular system - Abnormal NCS (week 0) to abnormal CS (week 26)	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Physical Examination Category Cardiovascular system - Abnormal CS (week 0) to normal (week 26)	—	—	—	0 Participants
Change From Baseline in Physical Examination Category Cardiovascular system - Abnormal CS (week 0) to abnormal NCS (week 26)	—	—	—	0 Participants
Change From Baseline in Physical Examination Category Cardiovascular system - Abnormal CS (week 0) to abnormal CS (week 26)	—	—	—	1 Participants
Change From Baseline in Physical Examination Category Central and Peripheral Nervous System - Normal (week 0) to normal (week 26)	119 Participants	121 Participants	116 Participants	120 Participants
Change From Baseline in Physical Examination Category Central and Peripheral Nervous System - Normal (week 0) to abnormal NCS (week 26)	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Physical Examination Category Central and Peripheral Nervous System - Normal (week 0) to abnormal CS (week 26)	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Physical Examination Category Central and Peripheral Nervous System - Abnormal NCS (week 0) to normal (week 26)	0 Participants	—	—	0 Participants
Change From Baseline in Physical Examination Category Central and Peripheral Nervous System - Abnormal NCS (week 0) to abnormal NCS (week 26)	2 Participants	—	—	1 Participants
Change From Baseline in Physical Examination Category Central and Peripheral Nervous System - Abnormal NCS (week 0) to abnormal CS (week 26)	0 Participants	—	—	0 Participants
Change From Baseline in Physical Examination Category Central and Peripheral Nervous System - Abnormal CS (week 0) to normal (week 26)	—	0 Participants	—	—
Change From Baseline in Physical Examination Category Central and Peripheral Nervous System - Abnormal CS (week 0) to abnormal NCS (week 26)	—	0 Participants	—	—
Change From Baseline in Physical Examination Category Central and Peripheral Nervous System - Abnormal CS (week 0) to abnormal CS (week 26)	—	1 Participants	—	—
Change From Baseline in Physical Examination Category Gastrointestinal System incl. Mouth - Normal (week 0) to normal (week 26)	117 Participants	117 Participants	114 Participants	115 Participants
Change From Baseline in Physical Examination Category Gastrointestinal System incl. Mouth - Normal (week 0) to abnormal NCS (week 26)	1 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Physical Examination Category Gastrointestinal System incl. Mouth - Normal (week 0) to abnormal CS (week 26)	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Physical Examination Category Gastrointestinal System incl. Mouth - Abnormal NCS (week 0) to normal (week 26)	2 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Physical Examination Category Gastrointestinal System incl. Mouth - Abnormal NCS (week 0) to abnormal NCS (week 26)	1 Participants	3 Participants	2 Participants	5 Participants
Change From Baseline in Physical Examination Category Gastrointestinal System incl. Mouth - Abnormal NCS (week 0) to abnormal CS (week 26)	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Physical Examination Category Gastrointestinal System incl. Mouth - Abnormal CS (week 0) to normal (week 26)	—	0 Participants	—	0 Participants
Change From Baseline in Physical Examination Category Gastrointestinal System incl. Mouth - Abnormal CS (week 0) to abnormal NCS (week 26)	—	0 Participants	—	0 Participants
Change From Baseline in Physical Examination Category Gastrointestinal System incl. Mouth - Abnormal CS (week 0) to abnormal CS (week 26)	—	2 Participants	—	1 Participants
Change From Baseline in Physical Examination Category General Appearance - Normal (week 0) to normal (week 26)	115 Participants	118 Participants	110 Participants	119 Participants
Change From Baseline in Physical Examination Category General Appearance - Normal (week 0) to abnormal NCS (week 26)	1 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Physical Examination Category General Appearance - Normal (week 0) to abnormal CS (week 26)	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Physical Examination Category General Appearance - Abnormal NCS (week 0) to normal (week 26)	4 Participants	2 Participants	1 Participants	0 Participants
Change From Baseline in Physical Examination Category General Appearance - Abnormal NCS (week 0) to abnormal NCS (week 26)	0 Participants	2 Participants	4 Participants	1 Participants
Change From Baseline in Physical Examination Category General Appearance - Abnormal NCS (week 0) to abnormal CS (week 26)	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Physical Examination Category General Appearance - Abnormal CS (week 0) to normal (week 26)	0 Participants	—	0 Participants	0 Participants
Change From Baseline in Physical Examination Category General Appearance - Abnormal CS (week 0) to abnormal NCS (week 26)	0 Participants	—	0 Participants	0 Participants
Change From Baseline in Physical Examination Category General Appearance - Abnormal CS (week 0) to abnormal CS (week 26)	1 Participants	—	1 Participants	1 Participants
Change From Baseline in Physical Examination Category Head, Ears, Eyes, Nose, Throat, Neck - Normal (week 0) to normal (week 26)	121 Participants	118 Participants	115 Participants	117 Participants
Change From Baseline in Physical Examination Category Thyroid Gland - Abnormal NCS (week 0) to abnormal CS (week 26)	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Physical Examination Category Thyroid Gland - Abnormal NCS (week 0) to normal (week 26)	0 Participants	0 Participants	0 Participants	0 Participants
Change From Baseline in Physical Examination Category Thyroid Gland - Abnormal NCS (week 0) to abnormal NCS (week 26)	2 Participants	2 Participants	3 Participants	1 Participants
Change From Baseline in Physical Examination Category Thyroid Gland - Abnormal CS (week 0) to normal (week 26)	—	—	—	0 Participants
Change From Baseline in Physical Examination Category Thyroid Gland - Abnormal CS (week 0) to abnormal NCS (week 26)	—	—	—	0 Participants
Change From Baseline in Physical Examination Category Thyroid Gland - Abnormal CS (week 0) to abnormal CS (week 26)	—	—	—	1 Participants

SECONDARY outcome

Timeframe: Baseline (Week 0), Week 26

Change from baseline (week 0) in eye examination category at week 26 is presented. Eye examination shift in findings were categorized as normal, abnormal NCS and 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, follow-up prematurely discontinuation visit, last date on trial product plus 38 days or the end-date for the in-trial observation period.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 3 mg n=120 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=121 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 4 to week 26.	Oral Semaglutide 14 mg n=119 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=121 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Change From Baseline in Eye Examination Category Left Eye Ophthalmoscopy - Abnormal NCS (week 0) to abnormal CS (week 26)	4 Participants	2 Participants	1 Participants	0 Participants
Change From Baseline in Eye Examination Category Left Eye Ophthalmoscopy - Normal (week 0) to normal (week 26)	73 Participants	77 Participants	83 Participants	75 Participants
Change From Baseline in Eye Examination Category Left Eye Ophthalmoscopy - Normal (week 0) to abnormal NCS (week 26)	6 Participants	5 Participants	5 Participants	5 Participants
Change From Baseline in Eye Examination Category Left Eye Ophthalmoscopy - Normal (week 0) to abnormal CS (week 26)	2 Participants	4 Participants	2 Participants	5 Participants
Change From Baseline in Eye Examination Category Left Eye Ophthalmoscopy - Abnormal NCS (week 0) to normal (week 26)	10 Participants	2 Participants	1 Participants	2 Participants
Change From Baseline in Eye Examination Category Left Eye Ophthalmoscopy - Abnormal NCS (week 0) to abnormal NCS (week 26)	15 Participants	19 Participants	15 Participants	18 Participants
Change From Baseline in Eye Examination Category Left Eye Ophthalmoscopy - Abnormal CS (week 0) to normal (week 26)	2 Participants	4 Participants	4 Participants	7 Participants
Change From Baseline in Eye Examination Category Left Eye Ophthalmoscopy - Abnormal CS (week 0) to abnormal NCS (week 26)	0 Participants	1 Participants	0 Participants	0 Participants
Change From Baseline in Eye Examination Category Left Eye Ophthalmoscopy - Abnormal CS (week 0) to abnormal CS (week 26)	8 Participants	7 Participants	8 Participants	9 Participants
Change From Baseline in Eye Examination Category Right Eye Ophthalmoscopy - Normal (week 0) to normal (week 26)	76 Participants	76 Participants	82 Participants	74 Participants
Change From Baseline in Eye Examination Category Right Eye Ophthalmoscopy - Normal (week 0) to abnormal NCS (week 26)	6 Participants	6 Participants	4 Participants	5 Participants
Change From Baseline in Eye Examination Category Right Eye Ophthalmoscopy - Normal (week 0) to abnormal CS (week 26)	3 Participants	4 Participants	3 Participants	3 Participants
Change From Baseline in Eye Examination Category Right Eye Ophthalmoscopy - Abnormal NCS (week 0) to normal (week 26)	8 Participants	3 Participants	3 Participants	3 Participants
Change From Baseline in Eye Examination Category Right Eye Ophthalmoscopy - Abnormal NCS (week 0) to abnormal NCS (week 26)	14 Participants	18 Participants	15 Participants	19 Participants
Change From Baseline in Eye Examination Category Right Eye Ophthalmoscopy - Abnormal NCS (week 0) to abnormal CS (week 26)	4 Participants	1 Participants	1 Participants	0 Participants
Change From Baseline in Eye Examination Category Right Eye Ophthalmoscopy - Abnormal CS (week 0) to normal (week 26)	2 Participants	3 Participants	5 Participants	8 Participants
Change From Baseline in Eye Examination Category Right Eye Ophthalmoscopy - Abnormal CS (week 0) to abnormal NCS (week 26)	0 Participants	1 Participants	1 Participants	0 Participants
Change From Baseline in Eye Examination Category Right Eye Ophthalmoscopy - Abnormal CS (week 0) to abnormal CS (week 26)	7 Participants	9 Participants	5 Participants	9 Participants

SECONDARY outcome

Timeframe: Up to 31 weeks

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

An adverse event (AE) is any untoward medical occurrence in a participant administered a medicinal product, and which does not necessarily have a causal relationship with this treatment. An AE can therefore be 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. TEAE was defined as an AE with onset in the on-treatment observation period. 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, follow-up prematurely discontinuation visit, last date on trial product plus 38 days or the end-date for the in-trial observation period.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 3 mg n=130 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=130 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 4 to week 26.	Oral Semaglutide 14 mg n=129 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=131 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Number of Treatment-emergent Adverse Events (TEAEs)	251 Events	292 Events	231 Events	212 Events

SECONDARY outcome

Timeframe: Up to 31 weeks

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

Severe or BG confirmed symptomatic hypoglycaemia was defined as an episode that was severe according to the ADA classification or BG confirmed by a plasma glucose (PG) value \<3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. 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, follow-up prematurely discontinuation visit, last date on trial product plus 38 days or the end-date for the in-trial observation period.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 3 mg n=130 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=130 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 4 to week 26.	Oral Semaglutide 14 mg n=129 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=131 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Number of Treatment-emergent Severe or Blood Glucose (BG) Confirmed Symptomatic Hypoglycaemic Episodes	0 Episodes	0 Episodes	0 Episodes	0 Episodes

SECONDARY outcome

Timeframe: Up to 31 weeks

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

Outcome measures

Outcome measures
Measure	Oral Semaglutide 3 mg n=130 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=130 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 4 to week 26.	Oral Semaglutide 14 mg n=129 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=131 Participants Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Number of Participants With Treatment-emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Up to 31 weeks

Anti-semaglutide binding antibody levels measured anytime during post-baseline visits (week 0 to week 31) are presented. The outcome data are presented as percentage of bound radioactivity-labelled semaglutide/total added radioactivity-labelled semaglutide (%B/T). Results are based on the data from the in-trial observation period - the in-trial observation period started at randomization and ended at the date of: the last direct participant-site contact, withdrawal for participants who withdrew their informed consent, the last participant-investigator contact, and death for participants who died before any of the above.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 3 mg Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=1 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 4 to week 26.	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 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Anti-semaglutide Binding Antibody Levels	—	2.1 %B/T	—	—

SECONDARY outcome

Timeframe: Up to 31 weeks

Number of participants who had anti-semaglutide binding antibody levels anytime during post-baseline visits (week 0 to week 31) are presented. Results are based on the data from the in-trial observation period - the in-trial observation period started at randomization and ended at the date of: the last direct participant-site contact, withdrawal for participants who withdrew their informed consent, the last participants-investigator contact, and death for participants who died before any of the above.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 3 mg n=91 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=93 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 4 to week 26.	Oral Semaglutide 14 mg n=85 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Number of Participants With Anti-semaglutide Binding Antibodies	0 Participants	1 Participants	0 Participants	—

SECONDARY outcome

Timeframe: Up to 31 weeks

Number of participants who had anti-semaglutide binding antibodies cross reacting with native glucagon-like peptide-1 (GLP-1) anytime during post-baseline visits (week 0 to week 31) are presented. Results are based on the data from the in-trial observation period - the in-trial observation period started at randomization and ended at the date of: the last direct participant-site contact, withdrawal for participants who withdrew their informed consent, the last participant-investigator contact, and death for participants who died before any of the above.

Outcome measures

Outcome measures
Measure	Oral Semaglutide 3 mg n=91 Participants Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=93 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 4 to week 26.	Oral Semaglutide 14 mg n=85 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Number of Participants With Anti-semaglutide Binding Antibodies Cross Reacting With Native GLP-1	0 Participants	0 Participants	0 Participants	—

Adverse Events

Oral Semaglutide 3 mg

Serious events: 6 serious events

Other events: 30 other events

Deaths: 0 deaths

Oral Semaglutide 7 mg

Serious events: 10 serious events

Other events: 47 other events

Deaths: 0 deaths

Oral Semaglutide 14 mg

Serious events: 5 serious events

Other events: 40 other events

Deaths: 0 deaths

Placebo

Serious events: 2 serious events

Other events: 16 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Oral Semaglutide 3 mg n=130 participants at risk Participants received oral semaglutide 3 mg tablets once daily from week 0 to week 26.	Oral Semaglutide 7 mg n=130 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 4 to week 26.	Oral Semaglutide 14 mg n=129 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, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Placebo n=131 participants at risk Participants received oral semaglutide matching placebo tablets once daily from week 0 to week 26.
Gastrointestinal disorders Abdominal distension	0.77% 1/130 • Number of events 1 • From week 0 to week 31 All presented adverse events (AEs) are treatment-emergent (i.e., TEAEs). TEAE was defined as an AE with onset in the on-treatment observation period. Results are based on the safety analysis set (SAS) which included all participants exposed to at least one dose of trial product.	7.7% 10/130 • Number of events 13 • From week 0 to week 31 All presented adverse events (AEs) are treatment-emergent (i.e., TEAEs). TEAE was defined as an AE with onset in the on-treatment observation period. Results are based on the safety analysis set (SAS) which included all participants exposed to at least one dose of trial product.	1.6% 2/129 • Number of events 2 • From week 0 to week 31 All presented adverse events (AEs) are treatment-emergent (i.e., TEAEs). TEAE was defined as an AE with onset in the on-treatment observation period. Results are based on the safety analysis set (SAS) which included all participants exposed to at least one dose of trial product.	0.76% 1/131 • Number of events 1 • From week 0 to week 31 All presented adverse events (AEs) are treatment-emergent (i.e., TEAEs). TEAE was defined as an AE with onset in the on-treatment observation period. Results are based on the safety analysis set (SAS) which included all participants exposed to at least one dose of trial product.
Gastrointestinal disorders Constipation	0.77% 1/130 • Number of events 1 • From week 0 to week 31 All presented adverse events (AEs) are treatment-emergent (i.e., TEAEs). TEAE was defined as an AE with onset in the on-treatment observation period. Results are based on the safety analysis set (SAS) which included all participants exposed to at least one dose of trial product.	5.4% 7/130 • Number of events 7 • From week 0 to week 31 All presented adverse events (AEs) are treatment-emergent (i.e., TEAEs). TEAE was defined as an AE with onset in the on-treatment observation period. Results are based on the safety analysis set (SAS) which included all participants exposed to at least one dose of trial product.	2.3% 3/129 • Number of events 3 • From week 0 to week 31 All presented adverse events (AEs) are treatment-emergent (i.e., TEAEs). TEAE was defined as an AE with onset in the on-treatment observation period. Results are based on the safety analysis set (SAS) which included all participants exposed to at least one dose of trial product.	0.00% 0/131 • From week 0 to week 31 All presented adverse events (AEs) are treatment-emergent (i.e., TEAEs). TEAE was defined as an AE with onset in the on-treatment observation period. Results are based on the safety analysis set (SAS) which included all participants exposed to at least one dose of trial product.
Metabolism and nutrition disorders Decreased appetite	1.5% 2/130 • Number of events 2 • From week 0 to week 31 All presented adverse events (AEs) are treatment-emergent (i.e., TEAEs). TEAE was defined as an AE with onset in the on-treatment observation period. Results are based on the safety analysis set (SAS) which included all participants exposed to at least one dose of trial product.	4.6% 6/130 • Number of events 7 • From week 0 to week 31 All presented adverse events (AEs) are treatment-emergent (i.e., TEAEs). TEAE was defined as an AE with onset in the on-treatment observation period. Results are based on the safety analysis set (SAS) which included all participants exposed to at least one dose of trial product.	10.9% 14/129 • Number of events 14 • From week 0 to week 31 All presented adverse events (AEs) are treatment-emergent (i.e., TEAEs). TEAE was defined as an AE with onset in the on-treatment observation period. Results are based on the safety analysis set (SAS) which included all participants exposed to at least one dose of trial product.	0.00% 0/131 • From week 0 to week 31 All presented adverse events (AEs) are treatment-emergent (i.e., TEAEs). TEAE was defined as an AE with onset in the on-treatment observation period. Results are based on the safety analysis set (SAS) which included all participants exposed to at least one dose of trial product.
Gastrointestinal disorders Diarrhoea	3.1% 4/130 • Number of events 4 • From week 0 to week 31 All presented adverse events (AEs) are treatment-emergent (i.e., TEAEs). TEAE was defined as an AE with onset in the on-treatment observation period. Results are based on the safety analysis set (SAS) which included all participants exposed to at least one dose of trial product.	9.2% 12/130 • Number of events 16 • From week 0 to week 31 All presented adverse events (AEs) are treatment-emergent (i.e., TEAEs). TEAE was defined as an AE with onset in the on-treatment observation period. Results are based on the safety analysis set (SAS) which included all participants exposed to at least one dose of trial product.	9.3% 12/129 • Number of events 18 • From week 0 to week 31 All presented adverse events (AEs) are treatment-emergent (i.e., TEAEs). TEAE was defined as an AE with onset in the on-treatment observation period. Results are based on the safety analysis set (SAS) which included all participants exposed to at least one dose of trial product.	1.5% 2/131 • Number of events 2 • From week 0 to week 31 All presented adverse events (AEs) are treatment-emergent (i.e., TEAEs). TEAE was defined as an AE with onset in the on-treatment observation period. Results are based on the safety analysis set (SAS) which included all participants exposed to at least one dose of trial product.
Metabolism and nutrition disorders Hyperlipidaemia	3.1% 4/130 • Number of events 4 • From week 0 to week 31 All presented adverse events (AEs) are treatment-emergent (i.e., TEAEs). TEAE was defined as an AE with onset in the on-treatment observation period. Results are based on the safety analysis set (SAS) which included all participants exposed to at least one dose of trial product.	2.3% 3/130 • Number of events 3 • From week 0 to week 31 All presented adverse events (AEs) are treatment-emergent (i.e., TEAEs). TEAE was defined as an AE with onset in the on-treatment observation period. Results are based on the safety analysis set (SAS) which included all participants exposed to at least one dose of trial product.	0.78% 1/129 • Number of events 1 • From week 0 to week 31 All presented adverse events (AEs) are treatment-emergent (i.e., TEAEs). TEAE was defined as an AE with onset in the on-treatment observation period. Results are based on the safety analysis set (SAS) which included all participants exposed to at least one dose of trial product.	5.3% 7/131 • Number of events 7 • From week 0 to week 31 All presented adverse events (AEs) are treatment-emergent (i.e., TEAEs). TEAE was defined as an AE with onset in the on-treatment observation period. Results are based on the safety analysis set (SAS) which included all participants exposed to at least one dose of trial product.
Investigations Lipase increased	5.4% 7/130 • Number of events 12 • From week 0 to week 31 All presented adverse events (AEs) are treatment-emergent (i.e., TEAEs). TEAE was defined as an AE with onset in the on-treatment observation period. Results are based on the safety analysis set (SAS) which included all participants exposed to at least one dose of trial product.	8.5% 11/130 • Number of events 12 • From week 0 to week 31 All presented adverse events (AEs) are treatment-emergent (i.e., TEAEs). TEAE was defined as an AE with onset in the on-treatment observation period. Results are based on the safety analysis set (SAS) which included all participants exposed to at least one dose of trial product.	3.1% 4/129 • Number of events 4 • From week 0 to week 31 All presented adverse events (AEs) are treatment-emergent (i.e., TEAEs). TEAE was defined as an AE with onset in the on-treatment observation period. Results are based on the safety analysis set (SAS) which included all participants exposed to at least one dose of trial product.	0.00% 0/131 • From week 0 to week 31 All presented adverse events (AEs) are treatment-emergent (i.e., TEAEs). TEAE was defined as an AE with onset in the on-treatment observation period. Results are based on the safety analysis set (SAS) which included all participants exposed to at least one dose of trial product.
Gastrointestinal disorders Nausea	4.6% 6/130 • Number of events 6 • From week 0 to week 31 All presented adverse events (AEs) are treatment-emergent (i.e., TEAEs). TEAE was defined as an AE with onset in the on-treatment observation period. Results are based on the safety analysis set (SAS) which included all participants exposed to at least one dose of trial product.	3.1% 4/130 • Number of events 4 • From week 0 to week 31 All presented adverse events (AEs) are treatment-emergent (i.e., TEAEs). TEAE was defined as an AE with onset in the on-treatment observation period. Results are based on the safety analysis set (SAS) which included all participants exposed to at least one dose of trial product.	6.2% 8/129 • Number of events 8 • From week 0 to week 31 All presented adverse events (AEs) are treatment-emergent (i.e., TEAEs). TEAE was defined as an AE with onset in the on-treatment observation period. Results are based on the safety analysis set (SAS) which included all participants exposed to at least one dose of trial product.	1.5% 2/131 • Number of events 2 • From week 0 to week 31 All presented adverse events (AEs) are treatment-emergent (i.e., TEAEs). TEAE was defined as an AE with onset in the on-treatment observation period. Results are based on the safety analysis set (SAS) which included all participants exposed to at least one dose of trial product.
Infections and infestations Upper respiratory tract infection	8.5% 11/130 • Number of events 12 • From week 0 to week 31 All presented adverse events (AEs) are treatment-emergent (i.e., TEAEs). TEAE was defined as an AE with onset in the on-treatment observation period. Results are based on the safety analysis set (SAS) which included all participants exposed to at least one dose of trial product.	9.2% 12/130 • Number of events 14 • From week 0 to week 31 All presented adverse events (AEs) are treatment-emergent (i.e., TEAEs). TEAE was defined as an AE with onset in the on-treatment observation period. Results are based on the safety analysis set (SAS) which included all participants exposed to at least one dose of trial product.	7.0% 9/129 • Number of events 12 • From week 0 to week 31 All presented adverse events (AEs) are treatment-emergent (i.e., TEAEs). TEAE was defined as an AE with onset in the on-treatment observation period. Results are based on the safety analysis set (SAS) which included all participants exposed to at least one dose of trial product.	4.6% 6/131 • Number of events 6 • From week 0 to week 31 All presented adverse events (AEs) are treatment-emergent (i.e., TEAEs). TEAE was defined as an AE with onset in the on-treatment observation period. Results are based on the safety analysis set (SAS) which included all participants exposed to at least one dose of trial product.

Additional Information

Clinical Reporting Office (2834)

Novo Nordisk A/S

Phone: (+1) 866-867-7178

Email: [email protected]

Results disclosure agreements

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

Restriction type: OTHER