PIONEER 3: Efficacy and Long-term Safety of Oral Semaglutide Versus Sitagliptin in Subjects With Type 2 Diabetes

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02607865
• Collaborator: (none)
• Enrollment: 1,864
• Locations: 242
• Arms: 4
• Actual Duration (Months): 25.4
• Patients Per Site: 7.7
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This trial is conducted globally. The aim of the trial is to investigate efficacy and long-term safety of oral semaglutide versus sitagliptin in subjects with type 2 diabetes.

Condition or Disease	Intervention/Treatment	Phase
Diabetes; Diabetes Mellitus, Type 2	Drug: semaglutide; Drug: sitagliptin; Drug: placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1864 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Efficacy and Long-term Safety of Oral Semaglutide Versus Sitagliptin in Subjects With Type 2 Diabetes
• Actual Study Start Date: Feb 15, 2016
• Actual Primary Completion Date: Feb 14, 2017
• Actual Study Completion Date: Mar 28, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Semaglutide 3 mg	Drug: semaglutide; Oral administration once-daily; Drug: placebo; Oral administration once-daily
Experimental: Semaglutide 7 mg	Drug: semaglutide; Oral administration once-daily; Drug: placebo; Oral administration once-daily
Experimental: Semaglutide 14 mg	Drug: semaglutide; Oral administration once-daily; Drug: placebo; Oral administration once-daily
Active Comparator: Sitagliptin 100 mg	Drug: sitagliptin; Oral administration once-daily; Drug: placebo; Oral administration once-daily

Outcome Measures

Primary Outcome Measures

1. Change in HbA1c: Week 26 [Week 0, week 26]

   Change from baseline (week 0) in glycosylated haemoglobin (HbA1c) was evaluated at week 26. The endpoint was evaluated based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. The endpoint was also evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.

Secondary Outcome Measures

1. Change in Body Weight: Week 26 [Week 0, week 26]

   Change from baseline (week 0) in body weight was evaluated at week 26. The endpoint was evaluated based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. The endpoint was also evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.

2. Change in HbA1c: Weeks 52 and 78 [Week 0, week 52, week 78]

   Change from baseline (week 0) in HbA1c was evaluated at weeks 52 and 78. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

3. Change in Body Weight (kg): Weeks 52 and 78 [Week 0, week 52, week 78]

   Change from baseline (week 0) in body weight was evaluated at weeks 52 and 78. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

4. Change in Body Weight (%) [Week 0, week 26, week 52, week 78]

   Relative change from baseline (week 0) in body weight (kg) was evaluated at weeks 26, 52 and 78. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

5. Change in FPG [Week 0, week 26, week 52, week 78]

   Change from baseline (week 0) in fasting plasma glucose (FPG) was evaluated at weeks 26, 52 and 78. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

6. Change in BMI [Week 0, week 26, week 52, week 78]

   Change from baseline (week 0) in body mass index (BMI) was evaluated at weeks 26, 52 and 78. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

7. Change in Waist Circumference [Week 0, week 26, week 52, week 78]

   Change from baseline (week 0) in waist circumference was evaluated at weeks 26, 52 and 78. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

8. Change in Total Cholesterol (Ratio to Baseline) [Week 0, week 26, week 52, week 78]

   Change from baseline (week 0) in total cholesterol (mmol/L) at weeks 26, 52 and 78 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

9. Change in LDL Cholesterol (Ratio to Baseline) [Week 0, week 26, week 52, week 78]

   Change from baseline (week 0) in low-density lipoprotein (LDL) cholesterol (mmol/L) at weeks 26, 52 and 78 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

10. Change in VLDL Cholesterol (Ratio to Baseline) [Week 0, week 26, week 52, week 78]

    Change from baseline (week 0) in very-low-density lipoprotein (VLDL) cholesterol (mmol/L) at weeks 26, 52 and 78 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

11. Change in HDL Cholesterol (Ratio to Baseline) [Week 0, week 26, week 52, week 78]

    Change from baseline (week 0) in high-density lipoprotein (HDL) cholesterol (mmol/L) at weeks 26, 52 and 78 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

12. Change in Triglycerides (Ratio to Baseline) [Week 0, week 26, week 52, week 78]

    Change from baseline (week 0) in triglycerides (mmol/L) at weeks 26, 52 and 78 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

13. Change in Free Fatty Acids (Ratio to Baseline) [Week 0, week 26, week 52, week 78]

    Change from baseline (week 0) in free fatty acids (FFA) (mmol/L) at weeks 26, 52 and 78 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. Because of an issue with the handling of the blood samples for FFA, all FFA data were considered invalid for this trial; thus, no conclusion with regards to FFA levels can be made based on the data presented here.

14. Change in SMPG - Mean 7-point Profile [Week 0, week 26, week 52, week 78]

    Change from baseline (week 0) in mean 7-point self-measured plasma glucose (SMPG) profile. 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. Mean 7-point profile was defined as the area under the profile, calculated using the trapezoidal method, divided by the measurement time. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

15. Change in SMPG - Mean Postprandial Increment Over All Meals [Week 0, week 26, week 52, week 78]

    Change from baseline (week 0) in the average of the post-prandial increments over all meals was evaluated at weeks 26, 52 and 78. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

16. Participants Who Achieve HbA1c <7.0% (53 mmol/Mol) ADA Target (Yes/no) [Week 26, week 52, week 78]

    Participants who achieved HbA1c <7.0% (American Diabetes Association (ADA) target) (yes/no), was evaluated at weeks 26, 52 and 78. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

17. Participants Who Achieve HbA1c ≤6.5% (48 mmol/Mol) AACE Target (Yes/no) [Week 26, week 52, week 78]

    Participants who achieved HbA1c less than or equal to 6.5% (American Association of Clinical Endocrinologists (AACE) target) (yes/no) at weeks 26, 52 and 78 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

18. Participants Who Achieve Weight Loss ≥5% (Yes/no) [Week 26, week 52, week 78]

    Participants who achieved weight loss more than or equal to 5% of their baseline body weight (yes/no) at weeks 26, 52 and 78 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

19. Participants Who Achieve Weight Loss ≥10% (Yes/no) [Week 26, week 52, week 78]

    Participants who achieved weight loss more than or equal to 10% of their baseline body weight (yes/no) at weeks 26, 52 and 78 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

20. Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no) [Week 26, week 52, week 78]

    Participants who achieved HbA1c less than 7.0 % without severe or blood glucose (BG) confirmed symptomatic hypoglycaemia and without weight gain (yes/no) at weeks 26, 52 and 78 are presented. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia was defined as an episode with plasma glucose value <3.1 mmol/L with symptoms consistent with hypoglycaemia. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

21. Participants Who Achieve HbA1c Reduction ≥1% (10.9 mmol/Mol) and Weight Loss ≥3% (Yes/no) [Week 26, week 52, week 78]

    Participants who achieved HbA1c reduction more than or equal to 1% of their baseline HbA1c and weight loss of more than or equal to 3% of their baseline body weight (yes/no) at weeks 26, 52 and 78 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

22. Time to Additional Anti-diabetic Medication [Weeks 0-78]

    Presented results are the number of participants who had taken additional anti-diabetic medication anytime during the periods, from week 0 to week 26, week 0 to week 52 and week 0 to week 78. Additional anti-diabetic medication was defined as any new anti-diabetic medication used for more than 21 days with the initiation at or after randomisation (week 0) and before (planned) end-of-treatment (week 78), and/or intensification of anti-diabetic medication (a more than 20% increase in dose relative to baseline) for more than 21 days with the intensification at or after randomisation and before (planned) end-of-treatment. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

23. Time to Rescue Medication [Weeks 0-78]

    Presented results are the number of participants who had taken rescue medication anytime during the periods, from week 0 to week 26, week 0 to week 52 and week 0 to week 78. 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 randomisation (week 0) and before last day on trial product, and/or intensification of anti-diabetic medication (a more than 20% increase in dose relative to baseline) for more than 21 days with the intensification at or after randomisation and before last day on trial product. Results are based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.

24. Number of TEAEs During Exposure to Trial Product [Weeks 0-83]

    Treatment emergent adverse events (TEAEs) were recorded from week 0 to week 83 (78-week treatment period plus the 5-week follow-up period). Adverse events (AEs) with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period: Time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

25. Change in Amylase (Ratio to Baseline) [Week 0, week 26, week 52, week 78]

    Change from baseline (week 0) in amylase (units/litre (U/L)) at weeks 26, 52 and 78 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

26. Change in Lipase (Ratio to Baseline) [Week 0, week 26, week 52, week 78]

    Change from baseline (week 0) in lipase (U/L) at weeks 26, 52 and 78 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

27. Change in Pulse Rate [Week 0, week 26, week 52, week 78]

    Change from baseline (week 0) in pulse rate was evaluated at weeks 26, 52 and 78. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

28. Change in SBP and DBP [Week 0, week 26, week 52, week 78]

    Change from baseline (week 0) in systolic blood pressure (SBP) and diastolic blood pressure (DBP) was evaluated at weeks 26, 52 and 78. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

29. Change in ECG Evaluation [Week 0, week 26, week 52, week 78]

    Change from baseline (week 0) in electrocardiogram (ECG) was evaluated at weeks 26, 52 and 78. Change from baseline results are presented as shift in findings (normal, abnormal and not clinically significant (NCS) and abnormal and clinically significant (CS)) from week 0 to week 26, 52 and 78. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

30. Change in Physical Examination [Week -2, week 52, week 78]

    Participants with physical examination findings, normal, abnormal NCS and abnormal CS at baseline (weeks -2), weeks 52 and 78 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. Results are presented for the following examinations: 1) Cardiovascular system; 2) Central and peripheral nervous system; 3) Gastrointestinal system, incl. mouth; 4) General appearance; 5) Head, ears, eyes, nose, throat, neck; 6) Lymph node palpation; 7) Musculoskeletal system; 8) Respiratory system; 9) Skin; 10) Thyroid gland.

31. Change in Eye Examination Category [Week -2, week 52, week 78]

    Participants with eye examination (fundoscopy) findings, normal, abnormal NCS and abnormal CS at baseline (week -2), week 52 and week 78 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

32. Occurrence of Anti-semaglutide Binding Antibodies (Yes/no) [Weeks 0-83]

    This outcome measure is only applicable for the oral semaglutide treatment arms (3 mg, 7 mg and 14 mg). Number of participants who measured with anti-semaglutide binding antibodies anytime during post-baseline visits (weeks 0-83) are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

33. Occurrence of Anti-semaglutide Neutralising Antibodies (Yes/no) [Weeks 0-83]

    This outcome measure is only applicable for the oral semaglutide treatment arms (3 mg, 7 mg and 14 mg). Number of participants who measured with anti-semaglutide neutralising antibodies anytime during post-baseline visits (weeks 0-83) are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

34. Occurrence of Anti-semaglutide Binding Antibodies Cross Reacting With Native GLP-1 (Yes/no) [Weeks 0-83]

    This outcome measure is only applicable for the oral semaglutide treatment arms (3 mg, 7 mg and 14 mg). Number of participants who measured with anti-semaglutide binding antibodies cross reacting with native glucagon-like peptide-1 (GLP-1) anytime during post-baseline visits (weeks 0-83) are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

35. Occurrence of Anti-semaglutide Neutralising Antibodies Cross Reacting With Native GLP-1 (Yes/no) [Weeks 0-83]

    This outcome measure is only applicable for the oral semaglutide treatment arms (3 mg, 7 mg and 14 mg). Number of participants who measured with anti-semaglutide neutralising antibodies cross reacting with native GLP-1 anytime during post-baseline visits (weeks 0-83) are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

36. Anti-semaglutide Binding Antibody Levels [Weeks 0-83]

    This outcome measure is only applicable for the oral semaglutide treatment arms (3 mg, 7 mg and 14 mg). It is based on the data from participants who were measured with anti-semaglutide antibodies anytime during post-baseline visits (weeks 0-83). Results 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, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

37. Number of Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes [Weeks 0-83]

    Treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes were recorded during weeks 0-83 (78-week treatment period plus the 5-week follow-up period). Hypoglycaemic episodes with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the time period when a subject was on treatment with trial product, including any period after initiation of rescue medication. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia: Confirmed by a glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.

38. Participants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes [Weeks 0-83]

    Treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes were recorded from week 0 to week 83 (78-week treatment period plus the 5-week follow-up period). Hypoglycaemic episodes with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the time period when a subject was on treatment with trial product, including any period after initiation of rescue medication. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia: Confirmed by a glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.

39. Semaglutide Plasma Concentration in a Subset of the Participants for Population PK Analyses [Weeks 0-83]

    This outcome measure is only applicable for the oral semaglutide treatment arms (3 mg, 7 mg and 14 mg). Semaglutide plasma concentrations for participants in the pharmacokinetic (PK) subpopulation are presented. The PK subpopulation consisted of participants from sites in Germany, Japan and the United States receiving oral semaglutide (3 mg, 7 mg or 14 mg). Results are based on the data from the on-treatment observation period and follow-up period. The on-treatment observation period was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

40. Change in SF-36v2 (Acute Version) Health Survey: Scores From the 8 Domains, the Physical Component Summary (PCS) and the Mental Component Summary (MCS) [Week 0, week 26, week 52, week 78]

    SF-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ (acute version) questionnaire measured eight domains of functional health and well-being as well as two component summary scores (physical component summary (PCS) and mental component summary (MCS)). The 0-100 scale scores (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. In the metric of norm-based scores, 50 and 10 corresponds to the mean and standard deviation respectively of the 2009 U.S. general population. Change from baseline (week 0) in the domain scores and component summary (PCS and MCS) scores were evaluated at weeks 26, 52 and 78. A positive change score indicates an improvement since baseline. Results are based on the data from the in-trial observation period.

41. Change in IWQoL-Lite-CT: Total Score and Scores From the 4 Domains [Week 0, week 26, week 52, week 78]

    The Impact of Weight on Quality of Life Clinical Trials Version (IWQOL-Lite-CT) is designed to assess the impact of changes in weight on patients' quality of life within the context of clinical trials. The items of the IWQOL-Lite-CT pertain to physical functioning (physical, physical function and pain/discomfort) and psychosocial domains and all items employ a 5-point graded response scale (never, rarely, sometimes, usually, always; or not at all true, a little true, moderately true, mostly true, completely true). All IWQOL-Lite-CT composite scores range from 0 to 100, with higher scores reflecting better levels of functioning. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

42. Change in CoEQ: Scores From the 4 Domains and the 19 Items [Week 0, week 26, week 52, week 78]

    Change from baseline (week 0) in Control of Eating Questionnaire (CoEQ) was evaluated at weeks (wk) 26, 52 and 78. The CoEQ comprised 19 items to assess the intensity and type of food cravings, as well as subjective sensation of appetite and mood, with the 4 domains: 'craving control' (items 9-12, 19), 'positive mood' (items 5-8), 'craving for savoury' (items 4, 16-18) and 'craving for sweet' (items 3, 13-15). The 19 items were scored on an 11-point graded response scale ranging from 10 to 0, with items relating to each of the 4 domains being averaged to create a final score. A low score in the domains 'craving for sweet and 'craving for savoury' represents a low level of craving; whereas a high score in the domains 'craving control' and 'positive mood' represents good control and a good mood, respectively. Results are based on the data from the in-trial observation period.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female, age at least 18 years at the time of signing informed consent For Japan only: Male or female, age at least 20 years at the time of signing informed consent

• Diagnosed with T2DM (type 2 diabetes mellitus) for at least 90 days prior to day of screening

• HbA1c (glycosylated haemoglobin) 7.0-10.5 % (53-91 mmol/mol) (both inclusive).

• Stable daily dose of metformin (equal or above 1500 mg or maximum tolerated dose as documented in subject medical record) alone or in combination with SU (= half of the maximum approved dose according to local label or maximum tolerated dose as documented in subject medical record) within 90 days prior to the day of screening

Exclusion Criteria:

• Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using adequate contraceptive methods (adequate contraceptive measures as required by local regulation or practice). For certain specific countries: Additional specific requirements apply

• Family or personal history of Multiple Endocrine Neoplasia Type 2 (MEN 2) or Medullary Thyroid Carcinoma (MTC)

• History of pancreatitis (acute or chronic)

• History of major surgical procedures involving the stomach potentially affecting absorption of trial product (e.g. subtotal and total gastrectomy, sleeve gastrectomy, gastric bypass surgery)

• Any of the following: myocardial infarction, stroke or hospitalization for unstable angina and/or transient ischaemic attack within the past 180 days prior to the day of screening

• Subjects presently classified as being in New York Heart Association (NYHA) Class IV.

• Planned coronary, carotid or peripheral artery revascularisation known on the day of screening.

• Renal impairment defined as estimated Glomerular Filtration Rate (eGFR) below 60 mL/min/1.73 m^2 as per Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)

• History or presence of malignant neoplasms within the last 5 years (except basal and squamous cell skin cancer and in-situ carcinomas)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Anniston	Alabama	United States	36207
2	Novo Nordisk Investigational Site	Birmingham	Alabama	United States	35211
3	Novo Nordisk Investigational Site	Tuscumbia	Alabama	United States	35674
4	Novo Nordisk Investigational Site	Glendale	Arizona	United States	85308
5	Novo Nordisk Investigational Site	Little Rock	Arkansas	United States	72212
6	Novo Nordisk Investigational Site	Carmichael	California	United States	95608
7	Novo Nordisk Investigational Site	Coronado	California	United States	92118
8	Novo Nordisk Investigational Site	Encino	California	United States	91436
9	Novo Nordisk Investigational Site	Fresno	California	United States	93720
10	Novo Nordisk Investigational Site	Los Alamitos	California	United States	90720
11	Novo Nordisk Investigational Site	Palm Springs	California	United States	92262
12	Novo Nordisk Investigational Site	Poway	California	United States	92064
13	Novo Nordisk Investigational Site	Walnut Creek	California	United States	94598
14	Novo Nordisk Investigational Site	Denver	Colorado	United States	80220
15	Novo Nordisk Investigational Site	Kissimmee	Florida	United States	34741
16	Novo Nordisk Investigational Site	New Port Richey	Florida	United States	34652
17	Novo Nordisk Investigational Site	Palm Harbor	Florida	United States	34684
18	Novo Nordisk Investigational Site	Plantation	Florida	United States	33324
19	Novo Nordisk Investigational Site	Port Charlotte	Florida	United States	33952
20	Novo Nordisk Investigational Site	Spring Hill	Florida	United States	34609
21	Novo Nordisk Investigational Site	Tampa	Florida	United States	33607
22	Novo Nordisk Investigational Site	Marietta	Georgia	United States	30060
23	Novo Nordisk Investigational Site	Perry	Georgia	United States	31069
24	Novo Nordisk Investigational Site	Honolulu	Hawaii	United States	96814
25	Novo Nordisk Investigational Site	Meridian	Idaho	United States	83646
26	Novo Nordisk Investigational Site	Gurnee	Illinois	United States	60031
27	Novo Nordisk Investigational Site	Peoria	Illinois	United States	61602
28	Novo Nordisk Investigational Site	Peoria	Illinois	United States	61603
29	Novo Nordisk Investigational Site	Avon	Indiana	United States	46123
30	Novo Nordisk Investigational Site	Park City	Kansas	United States	67219
31	Novo Nordisk Investigational Site	Lexington	Kentucky	United States	40503
32	Novo Nordisk Investigational Site	Louisville	Kentucky	United States	40213
33	Novo Nordisk Investigational Site	Paducah	Kentucky	United States	42001
34	Novo Nordisk Investigational Site	Paducah	Kentucky	United States	42003
35	Novo Nordisk Investigational Site	Metairie	Louisiana	United States	70002
36	Novo Nordisk Investigational Site	Natchitoches	Louisiana	United States	71457-5881
37	Novo Nordisk Investigational Site	Shreveport	Louisiana	United States	71105
38	Novo Nordisk Investigational Site	Rockville	Maryland	United States	20852
39	Novo Nordisk Investigational Site	Waltham	Massachusetts	United States	02453
40	Novo Nordisk Investigational Site	Flint	Michigan	United States	48532
41	Novo Nordisk Investigational Site	Sterling Heights	Michigan	United States	48310-3503
42	Novo Nordisk Investigational Site	Jefferson City	Missouri	United States	65109
43	Novo Nordisk Investigational Site	Butte	Montana	United States	59701-1652
44	Novo Nordisk Investigational Site	Teaneck	New Jersey	United States	07666
45	Novo Nordisk Investigational Site	Trenton	New Jersey	United States	08611
46	Novo Nordisk Investigational Site	Albuquerque	New Mexico	United States	87102
47	Novo Nordisk Investigational Site	New Windsor	New York	United States	12553
48	Novo Nordisk Investigational Site	Rochester	New York	United States	14607
49	Novo Nordisk Investigational Site	West Seneca	New York	United States	14224
50	Novo Nordisk Investigational Site	Charlotte	North Carolina	United States	28277
51	Novo Nordisk Investigational Site	High Point	North Carolina	United States	27265
52	Novo Nordisk Investigational Site	Statesville	North Carolina	United States	28625
53	Novo Nordisk Investigational Site	Whiteville	North Carolina	United States	28472
54	Novo Nordisk Investigational Site	Wilmington	North Carolina	United States	28401
55	Novo Nordisk Investigational Site	Fargo	North Dakota	United States	58104
56	Novo Nordisk Investigational Site	Cincinnati	Ohio	United States	45219
57	Novo Nordisk Investigational Site	Cincinnati	Ohio	United States	45236
58	Novo Nordisk Investigational Site	Columbus	Ohio	United States	43203
59	Novo Nordisk Investigational Site	Columbus	Ohio	United States	43213
60	Novo Nordisk Investigational Site	Franklin	Ohio	United States	45005
61	Novo Nordisk Investigational Site	Maumee	Ohio	United States	43537
62	Novo Nordisk Investigational Site	Toledo	Ohio	United States	43623
63	Novo Nordisk Investigational Site	Norman	Oklahoma	United States	73069
64	Novo Nordisk Investigational Site	Corvallis	Oregon	United States	97330-3737
65	Novo Nordisk Investigational Site	Jersey Shore	Pennsylvania	United States	17740
66	Novo Nordisk Investigational Site	McMurray	Pennsylvania	United States	15317
67	Novo Nordisk Investigational Site	Gaffney	South Carolina	United States	29341
68	Novo Nordisk Investigational Site	Greer	South Carolina	United States	29651
69	Novo Nordisk Investigational Site	Pelzer	South Carolina	United States	29669
70	Novo Nordisk Investigational Site	Summerville	South Carolina	United States	29485
71	Novo Nordisk Investigational Site	Bristol	Tennessee	United States	37620-7352
72	Novo Nordisk Investigational Site	Humboldt	Tennessee	United States	38343
73	Novo Nordisk Investigational Site	Jackson	Tennessee	United States	38305
74	Novo Nordisk Investigational Site	Amarillo	Texas	United States	79106
75	Novo Nordisk Investigational Site	Dallas	Texas	United States	75226
76	Novo Nordisk Investigational Site	Dallas	Texas	United States	75230
77	Novo Nordisk Investigational Site	Dallas	Texas	United States	75246
78	Novo Nordisk Investigational Site	Dallas	Texas	United States	75390-9302
79	Novo Nordisk Investigational Site	Houston	Texas	United States	77074
80	Novo Nordisk Investigational Site	Houston	Texas	United States	77081
81	Novo Nordisk Investigational Site	Longview	Texas	United States	75605
82	Novo Nordisk Investigational Site	Plano	Texas	United States	75093
83	Novo Nordisk Investigational Site	San Antonio	Texas	United States	78209
84	Novo Nordisk Investigational Site	San Antonio	Texas	United States	78224
85	Novo Nordisk Investigational Site	Sugar Land	Texas	United States	77478
86	Novo Nordisk Investigational Site	Waco	Texas	United States	76710
87	Novo Nordisk Investigational Site	Murray	Utah	United States	84123
88	Novo Nordisk Investigational Site	South Burlington	Vermont	United States	05403
89	Novo Nordisk Investigational Site	Richmond	Virginia	United States	23219
90	Novo Nordisk Investigational Site	Olympia	Washington	United States	98502
91	Novo Nordisk Investigational Site	Renton	Washington	United States	98057
92	Novo Nordisk Investigational Site	Spokane	Washington	United States	99218
93	Novo Nordisk Investigational Site	Milwaukee	Wisconsin	United States	53202
94	Novo Nordisk Investigational Site	Caba		Argentina	1425
95	Novo Nordisk Investigational Site	Caba		Argentina	C1060ABA
96	Novo Nordisk Investigational Site	Caba		Argentina	C1179AAB
97	Novo Nordisk Investigational Site	Capital Federal		Argentina	C1056ABJ
98	Novo Nordisk Investigational Site	Cordoba		Argentina	5000
99	Novo Nordisk Investigational Site	Córdoba		Argentina	5008
100	Novo Nordisk Investigational Site	São Paulo	Sao Paulo	Brazil	01228-200
101	Novo Nordisk Investigational Site	Angers		France	49000
102	Novo Nordisk Investigational Site	Chalons-en-Champagne Cedex		France	51005
103	Novo Nordisk Investigational Site	DIJON cedex		France	21079
104	Novo Nordisk Investigational Site	LA ROCHE-sur-YON cedex 9		France	85295
105	Novo Nordisk Investigational Site	LA ROCHELLE cedex		France	17019
106	Novo Nordisk Investigational Site	Le Creusot		France	71200
107	Novo Nordisk Investigational Site	Limoges		France	87000
108	Novo Nordisk Investigational Site	Marseille		France	13006
109	Novo Nordisk Investigational Site	Nanterre		France	92014
110	Novo Nordisk Investigational Site	Nantes Cedex 01		France	448093
111	Novo Nordisk Investigational Site	Nantes		France	44200
112	Novo Nordisk Investigational Site	Narbonne		France	11108
113	Novo Nordisk Investigational Site	Paris		France	75877
114	Novo Nordisk Investigational Site	PERPIGNAN cedex		France	66046
115	Novo Nordisk Investigational Site	Périgueux		France	24019
116	Novo Nordisk Investigational Site	Venissieux		France	69200
117	Novo Nordisk Investigational Site	Bad Mergentheim		Germany	97980
118	Novo Nordisk Investigational Site	Berlin		Germany	12163
119	Novo Nordisk Investigational Site	Dresden		Germany	01307
120	Novo Nordisk Investigational Site	Elsterwerda		Germany	04910
121	Novo Nordisk Investigational Site	Essen		Germany	45219
122	Novo Nordisk Investigational Site	Falkensee		Germany	14612
123	Novo Nordisk Investigational Site	Friedrichsthal		Germany	66299
124	Novo Nordisk Investigational Site	Hamburg		Germany	22607
125	Novo Nordisk Investigational Site	Leipzig		Germany	04103
126	Novo Nordisk Investigational Site	Münster		Germany	48145
127	Novo Nordisk Investigational Site	Saint Ingbert-Oberwürzbach		Germany	66386
128	Novo Nordisk Investigational Site	Stuttgart		Germany	70378
129	Novo Nordisk Investigational Site	Hyderabad	Andhra Pradesh	India	500034
130	Novo Nordisk Investigational Site	Hyderabad	Andhra Pradesh	India	500072
131	Novo Nordisk Investigational Site	Gurgaon	Haryana	India	122001
132	Novo Nordisk Investigational Site	Bangalore	Karnataka	India	560 017
133	Novo Nordisk Investigational Site	Mumbai	Maharashtra	India	4000016
134	Novo Nordisk Investigational Site	Mumbai	Maharashtra	India	400008
135	Novo Nordisk Investigational Site	Pune	Maharashtra	India	411040
136	Novo Nordisk Investigational Site	New Dehli	New Delhi	India	110029
137	Novo Nordisk Investigational Site	Bhubaneshwar	Orissa	India	751003
138	Novo Nordisk Investigational Site	Chandigarh	Punjab	India	160012
139	Novo Nordisk Investigational Site	Jaipur	Rajasthan	India	302004
140	Novo Nordisk Investigational Site	Jaipur	Rajasthan	India	302006
141	Novo Nordisk Investigational Site	Chennai	Tamil Nadu	India	600 013
142	Novo Nordisk Investigational Site	Chennai	Tamil Nadu	India	600086
143	Novo Nordisk Investigational Site	Vellore	Tamil Nadu	India	632004
144	Novo Nordisk Investigational Site	Kolkata	West Bengal	India	700014
145	Novo Nordisk Investigational Site	Kolkata	West Bengal	India	700020
146	Novo Nordisk Investigational Site	Kolkata	West Bengal	India	700064
147	Novo Nordisk Investigational Site	Haifa		Israel	31096
148	Novo Nordisk Investigational Site	Holon		Israel	58100
149	Novo Nordisk Investigational Site	Jerusalem		Israel	91120
150	Novo Nordisk Investigational Site	Kfar Saba		Israel	44281
151	Novo Nordisk Investigational Site	Petah-Tikva		Israel	49100
152	Novo Nordisk Investigational Site	Ra'anana		Israel	43452
153	Novo Nordisk Investigational Site	Tel Aviv		Israel	6937947
154	Novo Nordisk Investigational Site	Tel-Aviv		Israel	64239
155	Novo Nordisk Investigational Site	Asahikawa-shi, Hokkaido		Japan	070-0002
156	Novo Nordisk Investigational Site	Gunma		Japan	373-0036
157	Novo Nordisk Investigational Site	Hokkaido		Japan	060-0062
158	Novo Nordisk Investigational Site	Ibaraki		Japan	311-0113
159	Novo Nordisk Investigational Site	Iruma-shi, Saitama		Japan	358-0011
160	Novo Nordisk Investigational Site	Kanagawa		Japan	235-0045
161	Novo Nordisk Investigational Site	Kashiwara-shi, Osaka		Japan	582-0005
162	Novo Nordisk Investigational Site	Kyoto-shi, Kyoto		Japan	601-1495
163	Novo Nordisk Investigational Site	Kyoto-shi, Kyoto		Japan	615-0035
164	Novo Nordisk Investigational Site	Miyazaki		Japan	880-0034
165	Novo Nordisk Investigational Site	Osaka		Japan	569-1045
166	Novo Nordisk Investigational Site	Shinjuku-ku, Tokyo		Japan	162-8655
167	Novo Nordisk Investigational Site	Shizuoka-shi, Shizuoka		Japan	424-0853
168	Novo Nordisk Investigational Site	Tokyo		Japan	103-0027
169	Novo Nordisk Investigational Site	Tokyo		Japan	103-0028
170	Novo Nordisk Investigational Site	Tokyo		Japan	113-8431
171	Novo Nordisk Investigational Site	Toluca	Estado De México	Mexico	50130
172	Novo Nordisk Investigational Site	Guadalajara	Jalisco	Mexico	44670
173	Novo Nordisk Investigational Site	Ciudad Madero	Tamaulipas	Mexico	89440
174	Novo Nordisk Investigational Site	Aguascalientes		Mexico	20230
175	Novo Nordisk Investigational Site	San Luis Potosi		Mexico	78200
176	Novo Nordisk Investigational Site	Pitesti	Arges	Romania	110084
177	Novo Nordisk Investigational Site	Oradea	Bihor	Romania	410025
178	Novo Nordisk Investigational Site	Craiova	Dolj	Romania	200642
179	Novo Nordisk Investigational Site	Baia Mare	Maramures	Romania	430222
180	Novo Nordisk Investigational Site	Targu Mures	Mures	Romania	540098
181	Novo Nordisk Investigational Site	Ploiesti	Prahova	Romania	100342
182	Novo Nordisk Investigational Site	Timisoara	Timis	Romania	300125
183	Novo Nordisk Investigational Site	Bucharest		Romania	020359
184	Novo Nordisk Investigational Site	Bucharest		Romania	020475
185	Novo Nordisk Investigational Site	Iasi		Romania	700111
186	Novo Nordisk Investigational Site	Iasi		Romania	700469
187	Novo Nordisk Investigational Site	Satu Mare		Romania	440055
188	Novo Nordisk Investigational Site	Timisoara		Romania	300736
189	Novo Nordisk Investigational Site	Barnaul		Russian Federation	656045
190	Novo Nordisk Investigational Site	Moscow		Russian Federation	117036
191	Novo Nordisk Investigational Site	Moscow		Russian Federation	117292
192	Novo Nordisk Investigational Site	Moscow		Russian Federation	119435
193	Novo Nordisk Investigational Site	Novosibirsk		Russian Federation	630047
194	Novo Nordisk Investigational Site	Penza		Russian Federation	440026
195	Novo Nordisk Investigational Site	Tomsk		Russian Federation	634041
196	Novo Nordisk Investigational Site	Tomsk		Russian Federation	634050
197	Novo Nordisk Investigational Site	Yaroslavl		Russian Federation	150062
198	Novo Nordisk Investigational Site	Port Elizabeth	Eastern Cape	South Africa	6045
199	Novo Nordisk Investigational Site	Bloemfontein	Free State	South Africa	9301
200	Novo Nordisk Investigational Site	Johannesburg	Gauteng	South Africa	1818
201	Novo Nordisk Investigational Site	Johannesburg	Gauteng	South Africa	1829
202	Novo Nordisk Investigational Site	Johannesburg	Gauteng	South Africa	2001
203	Novo Nordisk Investigational Site	Johannesburg	Gauteng	South Africa	2198
204	Novo Nordisk Investigational Site	Krugersdorp	Gauteng	South Africa	1739
205	Novo Nordisk Investigational Site	Pretoria	Gauteng	South Africa	0122
206	Novo Nordisk Investigational Site	Durban	KwaZulu-Natal	South Africa	4120
207	Novo Nordisk Investigational Site	Cape Town	Western Cape	South Africa	7130
208	Novo Nordisk Investigational Site	Cape Town		South Africa	7530
209	Novo Nordisk Investigational Site	Pretoria		South Africa	0101
210	Novo Nordisk Investigational Site	Ankara		Turkey	06100
211	Novo Nordisk Investigational Site	Istanbul		Turkey	34147
212	Novo Nordisk Investigational Site	Istanbul		Turkey	34371
213	Novo Nordisk Investigational Site	Istanbul		Turkey	34718
214	Novo Nordisk Investigational Site	Istanbul		Turkey	34722
215	Novo Nordisk Investigational Site	İstanbul		Turkey	34752
216	Novo Nordisk Investigational Site	Istanbul		Turkey	34890
217	Novo Nordisk Investigational Site	Istanbul		Turkey
218	Novo Nordisk Investigational Site	Izmir		Turkey	35340
219	Novo Nordisk Investigational Site	Samsun		Turkey	55139
220	Novo Nordisk Investigational Site	Cherkasy		Ukraine	18009
221	Novo Nordisk Investigational Site	Ivano-Frankivsk		Ukraine	76018
222	Novo Nordisk Investigational Site	Kyiv		Ukraine	04114
223	Novo Nordisk Investigational Site	Mykolaiv		Ukraine	54003
224	Novo Nordisk Investigational Site	Odesa		Ukraine	65025
225	Novo Nordisk Investigational Site	Ternopil		Ukraine	46002
226	Novo Nordisk Investigational Site	Zaporizhia		Ukraine	69600
227	Novo Nordisk Investigational Site	Zhytomyr		Ukraine	10002
228	Novo Nordisk Investigational Site	Basingstoke		United Kingdom	RG24 9GT
229	Novo Nordisk Investigational Site	Cardiff		United Kingdom	CF5 4AD
230	Novo Nordisk Investigational Site	Chester		United Kingdom	CH2 1UL
231	Novo Nordisk Investigational Site	Crewe		United Kingdom	CW5 5NX
232	Novo Nordisk Investigational Site	Doncaster		United Kingdom	DN9 2HY
233	Novo Nordisk Investigational Site	Leicester		United Kingdom	LE5 4PW
234	Novo Nordisk Investigational Site	Plymouth		United Kingdom	PL6 8DH
235	Novo Nordisk Investigational Site	Preston		United Kingdom	PR2 9HT
236	Novo Nordisk Investigational Site	Rotherham		United Kingdom	S651DA
237	Novo Nordisk Investigational Site	Sidcup		United Kingdom	DA14 6LT
238	Novo Nordisk Investigational Site	Soham		United Kingdom	CB7 5JD
239	Novo Nordisk Investigational Site	Swansea		United Kingdom	SA2 8PP
240	Novo Nordisk Investigational Site	Taunton		United Kingdom	TA1 5DA
241	Novo Nordisk Investigational Site	Torquay		United Kingdom	TQ2 7AA
242	Novo Nordisk Investigational Site	Wellingborough		United Kingdom	NN8 4RW

Sponsors and Collaborators

• Novo Nordisk A/S

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Nov 21, 2018
• Statistical Analysis Plan - Nov 21, 2018

More Information

Additional Information:

• Clinical Trials at Novo Nordisk

Publications

None provided.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT02607865
• Other Study ID Numbers: NN9924-4222; 2015-001351-71; U1111-1168-4339; JAPIC
• First Posted: Nov 18, 2015
• Last Update Posted: Jul 20, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Sitagliptin Phosphate

Study Results

Participant Flow

Recruitment Details	The trial was conducted at 200 sites in 14 countries: Argentina-5, Brazil-1, France-10, Germany-12, Israel-8, Japan-16, Mexico-5, Romania-12, Russian Federation-8, South Africa-11, Turkey-7, Ukraine-8, United Kingdom (UK)-14, United States (US)-83. In addition, 6 sites screened, but didn't randomise any subjects: France-1, Turkey-1, UK-1 and US-3.
Pre-assignment Detail	Data presented in "participant flow" is based on the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.

Arm/Group Title	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg	Sitagliptin 100 mg
Arm/Group Description	Participants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take sitagliptin 100 mg tablets once daily from week 0 to week 78. In addition, participants were to take oral semaglutide placebo tablets once daily from week 0 to week 78.
Period Title: Overall Study
STARTED	466	466	465	467
Full Analysis Set (FAS)	466	465	465	467
Safety Analysis Set (SAS)	466	464	465	466
COMPLETED	433	436	438	451
NOT COMPLETED	33	30	27	16

Baseline Characteristics

Arm/Group Title	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg	Sitagliptin 100 mg	Total
Arm/Group Description	Participants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take sitagliptin 100 mg tablets once daily from week 0 to week 78. In addition, participants were to take oral semaglutide placebo tablets once daily from week 0 to week 78.	Total of all reporting groups
Overall Participants	466	465	465	467	1863
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58 (10)	58 (10)	57 (10)	58 (10)	58 (10)
Sex: Female, Male (Count of Participants)
Female	212 45.5%	220 47.3%	218 46.9%	229 49%	879 47.2%
Male	254 54.5%	245 52.7%	247 53.1%	238 51%	984 52.8%
Race/Ethnicity, Customized (Count of Participants)
White	344 73.8%	330 71%	317 68.2%	333 71.3%	1324 71.1%
Black or African American	38 8.2%	38 8.2%	45 9.7%	39 8.4%	160 8.6%
Asian	56 12%	69 14.8%	61 13.1%	59 12.6%	245 13.2%
American Indian or Alaska Native	4 0.9%	3 0.6%	5 1.1%	6 1.3%	18 1%
Native Hawaiian or other Pacific Islander	1 0.2%	0 0%	0 0%	0 0%	1 0.1%
Other	13 2.8%	11 2.4%	20 4.3%	12 2.6%	56 3%
Not applicable	10 2.1%	14 3%	17 3.7%	18 3.9%	59 3.2%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino	76 16.3%	77 16.6%	75 16.1%	93 19.9%	321 17.2%
Not Hispanic or Latino	385 82.6%	378 81.3%	377 81.1%	366 78.4%	1506 80.8%
Not applicable	5 1.1%	10 2.2%	13 2.8%	8 1.7%	36 1.9%
Glycosylated haemoglobin (HbA1c) (Percentage of HbA1c) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percentage of HbA1c]	8.3 (1.0)	8.4 (1.0)	8.3 (0.9)	8.3 (0.9)	8.3 (0.9)

Outcome Measures

1. Primary Outcome

Title	Change in HbA1c: Week 26
Description	Change from baseline (week 0) in glycosylated haemoglobin (HbA1c) was evaluated at week 26. The endpoint was evaluated based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. The endpoint was also evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = full analysis set (FAS) which comprised all randomised participants. Number Analyzed = number of participants with available data.

Arm/Group Title	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg	Sitagliptin 100 mg
Arm/Group Description	Participants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take sitagliptin 100 mg tablets once daily from week 0 to week 78. In addition, participants were to take oral semaglutide placebo tablets once daily from week 0 to week 78.
Measure Participants	466	465	465	467
In-trial	-0.6 (1.0)	-1.1 (1.1)	-1.3 (1.0)	-0.8 (0.9)
On-treatment without rescue medication	-0.6 (1.0)	-1.2 (1.1)	-1.4 (1.0)	-0.8 (0.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 14 mg, Sitagliptin 100 mg
	Comments	The analysis was based on a pattern mixture model using multiple imputation to handle missing week 26 data, assuming that data were missing at random within the groups used for imputation. The imputed data sets were analysed using an analysis of covariance (ANCOVA) model with treatment, strata, and region as categorical fixed effects and baseline HbA1c value as covariate for each of the 1000 imputed complete data sets, and pooled by Rubin's rule to draw inference.
	Type of Statistical Test	Non-Inferiority
	Comments	This hypothesis was controlled for multiplicity. Results are based on the data from the in-trial observation period. The estimated treatment effect includes the effect of any rescue medication and any effect after premature trial product discontinuation (treatment policy estimand). A value of 0.3% (the non-inferiority margin) was added to imputed values at week 26 for the oral semaglutide treatment arm only.
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Unadjusted two-sided p-value for test of no difference from the non-inferiority margin (non-inferiority). The non-inferiority margin was 0.3%.
	Method	Pattern mixture model
	Comments
Method of Estimation	Estimation Parameter	Mean treatment difference
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -0.6 to -0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 14 mg - Sitagliptin 100 mg

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 14 mg, Sitagliptin 100 mg
	Comments	The analysis was based on a pattern mixture model using multiple imputation to handle missing week 26 data, assuming that data were missing at random within the groups used for imputation. The imputed data sets were analysed using an ANCOVA model with treatment, strata, and region as categorical fixed effects and baseline HbA1c value as covariate for each of the 1000 imputed complete data sets, and pooled by Rubin's rule to draw inference.
	Type of Statistical Test	Superiority
	Comments	This hypothesis was controlled for multiplicity. Results are based on the data from the in-trial observation period. The estimated treatment effect includes the effect of any rescue medication and any effect after premature trial product discontinuation (treatment policy estimand).
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Unadjusted two-sided p-value for test of no difference from 0 (superiority).
	Method	Pattern mixture model
	Comments
Method of Estimation	Estimation Parameter	Mean treatment difference
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -0.6 to -0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 14 mg - Sitagliptin 100 mg

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 7 mg, Sitagliptin 100 mg
	Comments	The analysis was based on a pattern mixture model using multiple imputation to handle missing week 26 data, assuming that data were missing at random within the groups used for imputation. The imputed data sets were analysed using an ANCOVA model with treatment, strata, and region as categorical fixed effects and baseline HbA1c value as covariate for each of the 1000 imputed complete data sets, and pooled by Rubin's rule to draw inference.
	Type of Statistical Test	Non-Inferiority
	Comments	This hypothesis was controlled for multiplicity. Results are based on the data from the in-trial observation period. The estimated treatment effect includes the effect of any rescue medication and any effect after premature trial product discontinuation (treatment policy estimand). A value of 0.3% (the non-inferiority margin) was added to imputed values at week 26 for the oral semaglutide treatment arm only.
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Unadjusted two-sided p-value for test of no difference from the non-inferiority margin (non-inferiority). The non-inferiority margin was 0.3%.
	Method	Pattern mixture model
	Comments
Method of Estimation	Estimation Parameter	Mean treatment difference
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -0.4 to -0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 7 mg - Sitagliptin 100 mg

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 7 mg, Sitagliptin 100 mg
	Comments	The analysis was based on a pattern mixture model using multiple imputation to handle missing week 26 data, assuming that data were missing at random within the groups used for imputation. The imputed data sets were analysed using an ANCOVA model with treatment, strata, and region as categorical fixed effects and baseline HbA1c value as covariate for each of the 1000 imputed complete data sets, and pooled by Rubin's rule to draw inference.
	Type of Statistical Test	Superiority
	Comments	This hypothesis was controlled for multiplicity. Results are based on the data from the in-trial observation period. The estimated treatment effect includes the effect of any rescue medication and any effect after premature trial product discontinuation (treatment policy estimand).
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Unadjusted two-sided p-value for test of no difference from 0 (superiority).
	Method	Pattern mixture model
	Comments
Method of Estimation	Estimation Parameter	Mean treatment difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -0.4 to -0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 7 mg - Sitagliptin 100 mg

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 3 mg, Sitagliptin 100 mg
	Comments	The analysis was based on a pattern mixture model using multiple imputation to handle missing week 26 data, assuming that data were missing at random within the groups used for imputation. The imputed data sets were analysed using an ANCOVA model with treatment, strata, and region as categorical fixed effects and baseline HbA1c value as covariate for each of the 1000 imputed complete data sets, and pooled by Rubin's rule to draw inference.
	Type of Statistical Test	Non-Inferiority
	Comments	This hypothesis was controlled for multiplicity. Results are based on the data from the in-trial observation period. The estimated treatment effect includes the effect of any rescue medication and any effect after premature trial product discontinuation (treatment policy estimand). A value of 0.3% (the non-inferiority margin) was added to imputed values at week 26 for the oral semaglutide treatment arm only.
Statistical Test of Hypothesis	p-Value	= 0.0856
	Comments	Unadjusted two-sided p-value for test of no difference from the non-inferiority margin (non-inferiority). The non-inferiority margin was 0.3%.
	Method	Pattern mixture model
	Comments
Method of Estimation	Estimation Parameter	Mean treatment difference
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; 0.1 to 0.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 3 mg - Sitagliptin 100 mg

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 3 mg, Sitagliptin 100 mg
	Comments	The analysis was based on a pattern mixture model using multiple imputation to handle missing week 26 data, assuming that data were missing at random within the groups used for imputation. The imputed data sets were analysed using an ANCOVA model with treatment, strata, and region as categorical fixed effects and baseline HbA1c value as covariate for each of the 1000 imputed complete data sets, and pooled by Rubin's rule to draw inference.
	Type of Statistical Test	Superiority
	Comments	This hypothesis was not controlled for multiplicity, since the non-inferiority test of change in HbA1c for oral semaglutide 3 mg versus sitagliptin 100 mg could not be confirmed. Results are based on the data from the in-trial observation period. The estimated treatment effect includes the effect of any rescue medication and any effect after premature trial product discontinuation (treatment policy estimand).
Statistical Test of Hypothesis	p-Value	= 0.0080
	Comments	Unadjusted two-sided p-value for test of no difference from 0 (superiority).
	Method	Pattern mixture model
	Comments
Method of Estimation	Estimation Parameter	Mean treatment difference
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; 0.0 to 0.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 3 mg - Sitagliptin 100 mg. If the mean treatment difference is non-negative, the superiority hypothesis of oral semaglutide 3 mg vs sitagliptin 100 mg will never be confirmed irrespective of the observed two-sided p-value.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 14 mg, Sitagliptin 100 mg
	Comments	The analysis was based on a mixed model for repeated measurements (MMRM) that assumed data to be missing at random. As dependent variables, the MMRM model included all post-baseline values collected at scheduled visits up to and including week 26. The independent effects were treatment, strata and region as categorical fixed effects and the baseline HbA1c value as a covariate, all nested within visit, and an unstructured residual covariance matrix.
	Type of Statistical Test	Non-Inferiority
	Comments	This hypothesis was not controlled for multiplicity. Results are based on the data from the on-treatment without rescue medication observation period. The estimated treatment effect excludes the effect of any rescue medication and any effect after premature trial product discontinuation (hypothetical estimand).
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Unadjusted two-sided p-value for test of no difference from the non-inferiority margin (non-inferiority). The non-inferiority margin was 0.3%.
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Mean treatment difference
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -0.7 to -0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 14 mg - Sitagliptin 100 mg

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 14 mg, Sitagliptin 100 mg
	Comments	The analysis was based on a MMRM that assumed data to be missing at random. As dependent variables, the MMRM model included all post-baseline values collected at scheduled visits up to and including week 26. The independent effects were treatment, strata and region as categorical fixed effects and the baseline HbA1c value as a covariate, all nested within visit, and an unstructured residual covariance matrix.
	Type of Statistical Test	Superiority
	Comments	This hypothesis was not controlled for multiplicity. Results are based on the data from the on-treatment without rescue medication observation period. The estimated treatment effect excludes the effect of any rescue medication and any effect after premature trial product discontinuation (hypothetical estimand).
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Unadjusted two-sided p-value for test of no difference from 0 (superiority).
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Mean treatment difference
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -0.7 to -0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 14 mg - Sitagliptin 100 mg

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 7 mg, Sitagliptin 100 mg
	Comments	The analysis was based on a MMRM that assumed data to be missing at random. As dependent variables, the MMRM model included all post-baseline values collected at scheduled visits up to and including week 26. The independent effects were treatment, strata and region as categorical fixed effects and the baseline HbA1c value as a covariate, all nested within visit, and an unstructured residual covariance matrix.
	Type of Statistical Test	Non-Inferiority
	Comments	This hypothesis was not controlled for multiplicity. Results are based on the data from the on-treatment without rescue medication observation period. The estimated treatment effect excludes the effect of any rescue medication and any effect after premature trial product discontinuation (hypothetical estimand).
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Unadjusted two-sided p-value for test of no difference from the non-inferiority margin (non-inferiority). The non-inferiority margin was 0.3%.
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Mean treatment difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -0.4 to -0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 7 mg - Sitagliptin 100 mg

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 7 mg, Sitagliptin 100 mg
	Comments	The analysis was based on a MMRM that assumed data to be missing at random. As dependent variables, the MMRM model included all post-baseline values collected at scheduled visits up to and including week 26. The independent effects were treatment, strata and region as categorical fixed effects and the baseline HbA1c value as a covariate, all nested within visit, and an unstructured residual covariance matrix.
	Type of Statistical Test	Superiority
	Comments	This hypothesis was not controlled for multiplicity. Results are based on the data from the on-treatment without rescue medication observation period. The estimated treatment effect excludes the effect of any rescue medication and any effect after premature trial product discontinuation (hypothetical estimand).
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Unadjusted two-sided p-value for test of no difference from 0 (superiority).
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Mean treatment difference
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -0.4 to -0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 7 mg - Sitagliptin 100 mg

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 3 mg, Sitagliptin 100 mg
	Comments	The analysis was based on a MMRM that assumed data to be missing at random. As dependent variables, the MMRM model included all post-baseline values collected at scheduled visits up to and including week 26. The independent effects were treatment, strata and region as categorical fixed effects and the baseline HbA1c value as a covariate, all nested within visit, and an unstructured residual covariance matrix.
	Type of Statistical Test	Non-Inferiority
	Comments	This hypothesis was not controlled for multiplicity. Results are based on the data from the on-treatment without rescue medication observation period. The estimated treatment effect excludes the effect of any rescue medication and any effect after premature trial product discontinuation (hypothetical estimand).
Statistical Test of Hypothesis	p-Value	=0.3851
	Comments	Unadjusted two-sided p-value for test of no difference from the non-inferiority margin (non-inferiority). The non-inferiority margin was 0.3%.
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Mean treatment difference
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; 0.1 to 0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 3 mg - Sitagliptin 100 mg

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 3 mg, Sitagliptin 100 mg
	Comments	The analysis was based on a MMRM that assumed data to be missing at random. As dependent variables, the MMRM model included all post-baseline values collected at scheduled visits up to and including week 26. The independent effects were treatment, strata and region as categorical fixed effects and the baseline HbA1c value as a covariate, all nested within visit, and an unstructured residual covariance matrix.
	Type of Statistical Test	Other
	Comments	This hypothesis was not controlled for multiplicity. Results are based on the data from the on-treatment without rescue medication observation period. The estimated treatment effect excludes the effect of any rescue medication and any effect after premature trial product discontinuation (hypothetical estimand).
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Unadjusted two-sided p-value for test of no difference from 0 (superiority).
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Mean treatment difference
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; 0.1 to 0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 3 mg - Sitagliptin 100 mg. If the mean treatment difference is non-negative, the superiority hypothesis of oral semaglutide 3 mg vs sitagliptin 100 mg will never be confirmed irrespective of the observed two-sided p-value.

2. Secondary Outcome

Title	Change in Body Weight: Week 26
Description	Change from baseline (week 0) in body weight was evaluated at week 26. The endpoint was evaluated based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. The endpoint was also evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.
Time Frame	Week 0, week 26

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = FAS which comprised all randomised participants. Number Analyzed = number of participants with available data.

Arm/Group Title	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg	Sitagliptin 100 mg
Arm/Group Description	Participants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take sitagliptin 100 mg tablets once daily from week 0 to week 78. In addition, participants were to take oral semaglutide placebo tablets once daily from week 0 to week 78.
Measure Participants	466	465	465	467
In-trial	-1.2 (3.2)	-2.2 (3.9)	-3.1 (3.8)	-0.6 (3.2)
on-treatment without rescue medication	-1.2 (3.3)	-2.2 (4.0)	-3.2 (3.8)	-0.6 (3.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 14 mg, Sitagliptin 100 mg
	Comments	The analysis was based on a pattern mixture model using multiple imputation to handle missing week 26 data, assuming that data were missing at random within the groups used for imputation. The imputed data sets were analysed using an ANCOVA model with treatment, strata, and region as categorical fixed effects and baseline body weight value as covariate for each of the 1000 imputed complete data sets, and pooled by Rubin's rule to draw inference.
	Type of Statistical Test	Superiority
	Comments	This hypothesis was controlled for multiplicity. Results are based on the data from the in-trial observation period. The estimated treatment effect includes the effect of any rescue medication and any effect after premature trial product discontinuation (treatment policy estimand).
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Unadjusted two-sided p-value for test of no difference from 0 (superiority).
	Method	Pattern mixture model
	Comments
Method of Estimation	Estimation Parameter	Mean treatment difference
	Estimated Value	-2.5
	Confidence Interval	(2-Sided) 95%; -3.0 to -2.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 14 mg - Sitagliptin 100 mg

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 7 mg, Sitagliptin 100 mg
	Comments	The analysis was based on a pattern mixture model using multiple imputation to handle missing week 26 data, assuming that data were missing at random within the groups used for imputation. The imputed data sets were analysed using an ANCOVA model with treatment, strata, and region as categorical fixed effects and baseline body weight value as covariate for each of the 1000 imputed complete data sets, and pooled by Rubin's rule to draw inference.
	Type of Statistical Test	Superiority
	Comments	This hypothesis was controlled for multiplicity. Results are based on the data from the in-trial observation period. The estimated treatment effect includes the effect of any rescue medication and any effect after premature trial product discontinuation (treatment policy estimand).
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	Unadjusted two-sided p-value for test of no difference from 0 (superiority).
	Method	Pattern mixture model
	Comments
Method of Estimation	Estimation Parameter	Mean treatment difference
	Estimated Value	-1.6
	Confidence Interval	(2-Sided) 95%; -2.0 to -1.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 7 mg - Sitagliptin 100 mg

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 3 mg, Sitagliptin 100 mg
	Comments	The analysis was based on a pattern mixture model using multiple imputation to handle missing week 26 data, assuming that data were missing at random within the groups used for imputation. The imputed data sets were analysed using an ANCOVA model with treatment, strata, and region as categorical fixed effects and baseline body weight value as covariate for each of the 1000 imputed complete data sets, and pooled by Rubin's rule to draw inference.
	Type of Statistical Test	Superiority
	Comments	This hypothesis was not controlled for multiplicity, since the non-inferiority test of change in HbA1c for oral semaglutide 3 mg versus sitagliptin 100 mg could not be confirmed. Results are based on the data from the in-trial observation period. The estimated treatment effect includes the effect of any rescue medication and any effect after premature trial product discontinuation (treatment policy estimand).
Statistical Test of Hypothesis	p-Value	= 0.0185
	Comments	Unadjusted two-sided p-value for test of no difference from 0 (superiority).
	Method	Pattern mixture model
	Comments
Method of Estimation	Estimation Parameter	Mean treatment difference
	Estimated Value	-0.6
	Confidence Interval	(2-Sided) 95%; -1.1 to -0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 3 mg - Sitagliptin 100 mg

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 14 mg, Sitagliptin 100 mg
	Comments	The analysis was based on a MMRM that assumed data to be missing at random. As dependent variables, the MMRM model included all post-baseline values collected at scheduled visits up to and including week 26. The independent effects were treatment, strata and region as categorical fixed effects and the baseline body weight value as a covariate, all nested within visit, and an unstructured residual covariance matrix.
	Type of Statistical Test	Superiority
	Comments	This hypothesis was not controlled for multiplicity. Results are based on the data from the on-treatment without rescue medication observation period. The estimated treatment effect excludes the effect of any rescue medication and any effect after premature trial product discontinuation (hypothetical estimand).
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Unadjusted two-sided p-value for test of no difference from 0 (superiority).
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Mean treatment difference
	Estimated Value	-2.6
	Confidence Interval	(2-Sided) 95%; -3.1 to -2.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 14 mg - Sitagliptin 100 mg

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 7 mg, Sitagliptin 100 mg
	Comments	The analysis was based on a MMRM that assumed data to be missing at random. As dependent variables, the MMRM model included all post-baseline values collected at scheduled visits up to and including week 26. The independent effects were treatment, strata and region as categorical fixed effects and the baseline body weight value as a covariate, all nested within visit, and an unstructured residual covariance matrix.
	Type of Statistical Test	Superiority
	Comments	This hypothesis was not controlled for multiplicity. Results are based on the data from the on-treatment without rescue medication observation period. The estimated treatment effect excludes the effect of any rescue medication and any effect after premature trial product discontinuation (hypothetical estimand).
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Unadjusted two-sided p-value for test of no difference from 0 (superiority).
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Mean treatment difference
	Estimated Value	-1.5
	Confidence Interval	(2-Sided) 95%; -2.0 to -1.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 7 mg - Sitagliptin 100 mg

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 3 mg, Sitagliptin 100 mg
	Comments	The analysis was based on a MMRM that assumed data to be missing at random. As dependent variables, the MMRM model included all post-baseline values collected at scheduled visits up to and including week 26. The independent effects were treatment, strata and region as categorical fixed effects and the baseline body weight value as a covariate, all nested within visit, and an unstructured residual covariance matrix.
	Type of Statistical Test	Superiority
	Comments	This hypothesis was not controlled for multiplicity. Results are based on the data from the on-treatment without rescue medication observation period. The estimated treatment effect excludes the effect of any rescue medication and any effect after premature trial product discontinuation (hypothetical estimand).
Statistical Test of Hypothesis	p-Value	=0.0257
	Comments	Unadjusted two-sided p-value for test of no difference from 0 (superiority).
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	type Mean treatment difference
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -1.0 to -0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 3 mg - Sitagliptin 100 mg

3. Secondary Outcome

Title	Change in HbA1c: Weeks 52 and 78
Description	Change from baseline (week 0) in HbA1c was evaluated at weeks 52 and 78. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame	Week 0, week 52, week 78

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = FAS which comprised all randomised participants. Number Analyzed = number of participants with available data.

Arm/Group Title	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg	Sitagliptin 100 mg
Arm/Group Description	Participants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take sitagliptin 100 mg tablets once daily from week 0 to week 78. In addition, participants were to take oral semaglutide placebo tablets once daily from week 0 to week 78.
Measure Participants	466	465	465	467
Week 52	-0.6 (1.1)	-1.0 (1.2)	-1.2 (1.1)	-0.7 (1.1)
Week 78	-0.6 (1.1)	-0.9 (1.3)	-1.1 (1.1)	-0.7 (1.1)

4. Secondary Outcome

Title	Change in Body Weight (kg): Weeks 52 and 78
Description	Change from baseline (week 0) in body weight was evaluated at weeks 52 and 78. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame	Week 0, week 52, week 78

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = FAS which comprised all randomised participants. Number Analyzed = number of participants with available data.

Arm/Group Title	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg	Sitagliptin 100 mg
Arm/Group Description	Participants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take sitagliptin 100 mg tablets once daily from week 0 to week 78. In addition, participants were to take oral semaglutide placebo tablets once daily from week 0 to week 78.
Measure Participants	466	465	465	467
Week 52	-1.6 (4.1)	-2.5 (4.9)	-3.5 (4.7)	-0.7 (3.7)
Week 78	-1.8 (4.9)	-2.8 (5.4)	-3.2 (4.9)	-1.0 (4.1)

5. Secondary Outcome

Title	Change in Body Weight (%)
Description	Relative change from baseline (week 0) in body weight (kg) was evaluated at weeks 26, 52 and 78. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame	Week 0, week 26, week 52, week 78

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = FAS which comprised all randomised participants. Number Analyzed = number of participants with available data.

Arm/Group Title	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg	Sitagliptin 100 mg
Arm/Group Description	Participants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take sitagliptin 100 mg tablets once daily from week 0 to week 78. In addition, participants were to take oral semaglutide placebo tablets once daily from week 0 to week 78.
Measure Participants	466	465	465	467
Week 26	-1.23 (3.57)	-2.36 (4.09)	-3.44 (4.21)	-0.64 (3.38)
Week 52	-1.65 (4.28)	-2.63 (5.09)	-3.83 (5.14)	-0.76 (3.91)
Week 78	-1.87 (4.87)	-2.92 (5.67)	-3.47 (5.34)	-0.99 (4.39)

6. Secondary Outcome

Title	Change in FPG
Description	Change from baseline (week 0) in fasting plasma glucose (FPG) was evaluated at weeks 26, 52 and 78. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame	Week 0, week 26, week 52, week 78

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = FAS which comprised all randomised participants. Number Analyzed = number of participants with available data.

Arm/Group Title	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg	Sitagliptin 100 mg
Arm/Group Description	Participants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take sitagliptin 100 mg tablets once daily from week 0 to week 78. In addition, participants were to take oral semaglutide placebo tablets once daily from week 0 to week 78.
Measure Participants	466	465	465	467
Week 26	-0.83 (2.69)	-1.17 (2.54)	-1.67 (2.60)	-0.90 (2.32)
Week 52	-0.98 (2.78)	-1.28 (2.62)	-1.75 (2.57)	-1.03 (2.60)
Week 78	-1.07 (3.21)	-1.11 (2.92)	-1.65 (2.71)	-0.91 (2.59)

7. Secondary Outcome

Title	Change in BMI
Description	Change from baseline (week 0) in body mass index (BMI) was evaluated at weeks 26, 52 and 78. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame	Week 0, week 26, week 52, week 78

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = FAS which comprised all randomised participants. Number Analyzed = number of participants with available data.

Arm/Group Title	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg	Sitagliptin 100 mg
Arm/Group Description	Participants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take sitagliptin 100 mg tablets once daily from week 0 to week 78. In addition, participants were to take oral semaglutide placebo tablets once daily from week 0 to week 78.
Measure Participants	466	465	465	467
Week 26	-0.4 (1.2)	-0.8 (1.4)	-1.1 (1.4)	-0.2 (1.1)
Week 52	-0.6 (1.5)	-0.9 (1.7)	-1.2 (1.7)	-0.3 (1.3)
Week 78	-0.7 (1.8)	-1.0 (1.9)	-1.1 (1.7)	-0.4 (1.5)

8. Secondary Outcome

Title	Change in Waist Circumference
Description	Change from baseline (week 0) in waist circumference was evaluated at weeks 26, 52 and 78. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame	Week 0, week 26, week 52, week 78

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = FAS which comprised all randomised participants. Number Analyzed = number of participants with available data.

Arm/Group Title	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg	Sitagliptin 100 mg
Arm/Group Description	Participants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take sitagliptin 100 mg tablets once daily from week 0 to week 78. In addition, participants were to take oral semaglutide placebo tablets once daily from week 0 to week 78.
Measure Participants	466	465	465	467
Week 26	-0.7 (5.0)	-1.8 (5.2)	-2.3 (5.2)	-0.6 (4.4)
Week 52	-1.3 (5.7)	-2.3 (6.8)	-2.6 (6.2)	-0.5 (5.1)
Week 78	-1.2 (6.0)	-2.4 (7.2)	-2.4 (6.1)	-0.7 (5.6)

9. Secondary Outcome

Title	Change in Total Cholesterol (Ratio to Baseline)
Description	Change from baseline (week 0) in total cholesterol (mmol/L) at weeks 26, 52 and 78 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame	Week 0, week 26, week 52, week 78

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = FAS which comprised all randomised participants. Number Analyzed = number of participants with available data.

Arm/Group Title	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg	Sitagliptin 100 mg
Arm/Group Description	Participants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take sitagliptin 100 mg tablets once daily from week 0 to week 78. In addition, participants were to take oral semaglutide placebo tablets once daily from week 0 to week 78.
Measure Participants	466	465	465	467
Week 26	1.00 (16.8)	0.98 (17.5)	0.97 (17.1)	1.00 (16.4)
Week 52	1.00 (17.5)	0.99 (18.5)	0.98 (17.0)	1.01 (16.9)
Week 78	1.00 (18.3)	0.99 (19.3)	0.99 (18.7)	1.00 (19.4)

10. Secondary Outcome

Title	Change in LDL Cholesterol (Ratio to Baseline)
Description	Change from baseline (week 0) in low-density lipoprotein (LDL) cholesterol (mmol/L) at weeks 26, 52 and 78 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame	Week 0, week 26, week 52, week 78

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = FAS which comprised all randomised participants. Number Analyzed = number of participants with available data.

Arm/Group Title	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg	Sitagliptin 100 mg
Arm/Group Description	Participants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take sitagliptin 100 mg tablets once daily from week 0 to week 78. In addition, participants were to take oral semaglutide placebo tablets once daily from week 0 to week 78.
Measure Participants	466	465	465	467
Week 26	1.02 (28.2)	0.98 (28.0)	0.98 (28.6)	1.02 (26.4)
Week 52	1.02 (28.1)	0.99 (29.7)	0.99 (27.4)	1.03 (27.7)
Week 78	1.03 (30.8)	1.00 (30.2)	1.00 (30.2)	1.03 (32.6)

11. Secondary Outcome

Title	Change in VLDL Cholesterol (Ratio to Baseline)
Description	Change from baseline (week 0) in very-low-density lipoprotein (VLDL) cholesterol (mmol/L) at weeks 26, 52 and 78 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame	Week 0, week 26, week 52, week 78

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = FAS which comprised all randomised participants. Number Analyzed = number of participants with available data.

Arm/Group Title	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg	Sitagliptin 100 mg
Arm/Group Description	Participants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take sitagliptin 100 mg tablets once daily from week 0 to week 78. In addition, participants were to take oral semaglutide placebo tablets once daily from week 0 to week 78.
Measure Participants	466	465	465	467
Week 26	0.99 (36.4)	0.96 (36.1)	0.91 (36.3)	0.97 (34.1)
Week 52	1.00 (35.0)	0.98 (39.1)	0.93 (39.6)	0.98 (34.4)
Week 78	0.95 (41.7)	0.94 (41.5)	0.91 (40.4)	0.94 (39.6)

12. Secondary Outcome

Title	Change in HDL Cholesterol (Ratio to Baseline)
Description	Change from baseline (week 0) in high-density lipoprotein (HDL) cholesterol (mmol/L) at weeks 26, 52 and 78 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame	Week 0, week 26, week 52, week 78

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = FAS which comprised all randomised participants. Number Analyzed = number of participants with available data.

Arm/Group Title	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg	Sitagliptin 100 mg
Arm/Group Description	Participants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take sitagliptin 100 mg tablets once daily from week 0 to week 78. In addition, participants were to take oral semaglutide placebo tablets once daily from week 0 to week 78.
Measure Participants	466	465	465	467
Week 26	0.97 (13.6)	0.99 (14.8)	0.98 (14.9)	0.99 (12.6)
Week 52	0.99 (13.9)	1.01 (14.3)	1.01 (15.2)	0.99 (15.9)
Week 78	0.97 (15.3)	0.99 (15.6)	1.00 (15.5)	0.99 (14.2)

13. Secondary Outcome

Title	Change in Triglycerides (Ratio to Baseline)
Description	Change from baseline (week 0) in triglycerides (mmol/L) at weeks 26, 52 and 78 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame	Week 0, week 26, week 52, week 78

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = FAS which comprised all randomised participants. Number Analyzed = number of participants with available data.

Arm/Group Title	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg	Sitagliptin 100 mg
Arm/Group Description	Participants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take sitagliptin 100 mg tablets once daily from week 0 to week 78. In addition, participants were to take oral semaglutide placebo tablets once daily from week 0 to week 78.
Measure Participants	466	465	465	467
Week 26	0.99 (38.1)	0.96 (39.2)	0.92 (39.8)	0.97 (36.2)
Week 52	1.00 (35.7)	0.97 (41.3)	0.93 (42.3)	0.98 (37.8)
Week 78	0.95 (43.9)	0.94 (43.7)	0.92 (43.1)	0.93 (41.6)

14. Secondary Outcome

Title	Change in Free Fatty Acids (Ratio to Baseline)
Description	Change from baseline (week 0) in free fatty acids (FFA) (mmol/L) at weeks 26, 52 and 78 is presented as ratio to baseline. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. Because of an issue with the handling of the blood samples for FFA, all FFA data were considered invalid for this trial; thus, no conclusion with regards to FFA levels can be made based on the data presented here.
Time Frame	Week 0, week 26, week 52, week 78

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = FAS which comprised all randomised participants. Number Analyzed = number of participants with available data.

Arm/Group Title	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg	Sitagliptin 100 mg
Arm/Group Description	Participants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take sitagliptin 100 mg tablets once daily from week 0 to week 78. In addition, participants were to take oral semaglutide placebo tablets once daily from week 0 to week 78.
Measure Participants	466	465	465	467
Week 26	0.96 (48.7)	0.91 (50.4)	0.88 (55.8)	0.90 (49.8)
Week 52	1.03 (46.7)	1.00 (47.9)	0.96 (56.0)	0.98 (47.5)
Week 78	0.92 (54.2)	0.87 (56.5)	0.88 (56.3)	0.87 (57.8)

15. Secondary Outcome

Title	Change in SMPG - Mean 7-point Profile
Description	Change from baseline (week 0) in mean 7-point self-measured plasma glucose (SMPG) profile. 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. Mean 7-point profile was defined as the area under the profile, calculated using the trapezoidal method, divided by the measurement time. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame	Week 0, week 26, week 52, week 78

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = FAS which comprised all randomised participants. Number Analyzed = number of participants with available data.

Arm/Group Title	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg	Sitagliptin 100 mg
Arm/Group Description	Participants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take sitagliptin 100 mg tablets once daily from week 0 to week 78. In addition, participants were to take oral semaglutide placebo tablets once daily from week 0 to week 78.
Measure Participants	466	465	465	467
Week 26	-1.1 (2.3)	-1.5 (2.3)	-1.7 (2.4)	-1.2 (2.3)
Week 52	-1.3 (2.4)	-1.5 (2.5)	-1.8 (2.4)	-1.4 (2.4)
Week 78	-1.3 (2.7)	-1.5 (2.7)	-1.7 (2.2)	-1.3 (2.5)

16. Secondary Outcome

Title	Change in SMPG - Mean Postprandial Increment Over All Meals
Description	Change from baseline (week 0) in the average of the post-prandial increments over all meals was evaluated at weeks 26, 52 and 78. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame	Week 0, week 26, week 52, week 78

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = FAS which comprised all randomised participants. Number Analyzed = number of participants with available data.

Arm/Group Title	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg	Sitagliptin 100 mg
Arm/Group Description	Participants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take sitagliptin 100 mg tablets once daily from week 0 to week 78. In addition, participants were to take oral semaglutide placebo tablets once daily from week 0 to week 78.
Measure Participants	466	465	465	467
Week 26	-0.4 (2.1)	-0.4 (2.1)	-0.6 (2.1)	-0.6 (2.1)
Week 52	-0.4 (2.0)	-0.4 (2.1)	-0.7 (2.0)	-0.4 (2.1)
Week 78	-0.4 (2.1)	-0.4 (2.1)	-0.6 (2.0)	-0.6 (2.2)

17. Secondary Outcome

Title	Participants Who Achieve HbA1c <7.0% (53 mmol/Mol) ADA Target (Yes/no)
Description	Participants who achieved HbA1c <7.0% (American Diabetes Association (ADA) target) (yes/no), was evaluated at weeks 26, 52 and 78. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame	Week 26, week 52, week 78

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = FAS which comprised all randomised participants. Number Analyzed = number of participants with available data.

Arm/Group Title	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg	Sitagliptin 100 mg
Arm/Group Description	Participants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take sitagliptin 100 mg tablets once daily from week 0 to week 78. In addition, participants were to take oral semaglutide placebo tablets once daily from week 0 to week 78.
Measure Participants	466	465	465	467
Yes	116 24.9%	192 41.3%	246 52.9%	144 30.8%
No	319 68.5%	246 52.9%	190 40.9%	302 64.7%
Yes	113 24.2%	168 36.1%	238 51.2%	138 29.6%
No	314 67.4%	263 56.6%	196 42.2%	298 63.8%
Yes	113 24.2%	165 35.5%	191 41.1%	129 27.6%
No	308 66.1%	259 55.7%	234 50.3%	310 66.4%

18. Secondary Outcome

Title	Participants Who Achieve HbA1c ≤6.5% (48 mmol/Mol) AACE Target (Yes/no)
Description	Participants who achieved HbA1c less than or equal to 6.5% (American Association of Clinical Endocrinologists (AACE) target) (yes/no) at weeks 26, 52 and 78 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame	Week 26, week 52, week 78

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = FAS which comprised all randomised participants. Number Analyzed = number of participants with available data.

Arm/Group Title	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg	Sitagliptin 100 mg
Arm/Group Description	Participants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take sitagliptin 100 mg tablets once daily from week 0 to week 78. In addition, participants were to take oral semaglutide placebo tablets once daily from week 0 to week 78.
Measure Participants	466	465	465	467
Yes	55 11.8%	116 24.9%	161 34.6%	61 13.1%
No	380 81.5%	322 69.2%	275 59.1%	385 82.4%
Yes	55 11.8%	99 21.3%	146 31.4%	59 12.6%
No	372 79.8%	332 71.4%	288 61.9%	377 80.7%
Yes	49 10.5%	100 21.5%	129 27.7%	60 12.8%
No	372 79.8%	324 69.7%	296 63.7%	379 81.2%

19. Secondary Outcome

Title	Participants Who Achieve Weight Loss ≥5% (Yes/no)
Description	Participants who achieved weight loss more than or equal to 5% of their baseline body weight (yes/no) at weeks 26, 52 and 78 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame	Week 26, week 52, week 78

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = FAS which comprised all randomised participants. Number Analyzed = number of participants with available data.

Arm/Group Title	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg	Sitagliptin 100 mg
Arm/Group Description	Participants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take sitagliptin 100 mg tablets once daily from week 0 to week 78. In addition, participants were to take oral semaglutide placebo tablets once daily from week 0 to week 78.
Measure Participants	466	465	465	467
Yes	53 11.4%	81 17.4%	131 28.2%	45 9.6%
No	385 82.6%	359 77.2%	308 66.2%	402 86.1%
Yes	66 14.2%	118 25.4%	147 31.6%	50 10.7%
No	362 77.7%	315 67.7%	288 61.9%	387 82.9%
Yes	83 17.8%	115 24.7%	139 29.9%	59 12.6%
No	342 73.4%	310 66.7%	289 62.2%	384 82.2%

20. Secondary Outcome

Title	Participants Who Achieve Weight Loss ≥10% (Yes/no)
Description	Participants who achieved weight loss more than or equal to 10% of their baseline body weight (yes/no) at weeks 26, 52 and 78 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame	Week 26, week 52, week 78

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = FAS which comprised all randomised participants. Number Analyzed = number of participants with available data.

Arm/Group Title	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg	Sitagliptin 100 mg
Arm/Group Description	Participants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take sitagliptin 100 mg tablets once daily from week 0 to week 78. In addition, participants were to take oral semaglutide placebo tablets once daily from week 0 to week 78.
Measure Participants	466	465	465	467
Yes	5 1.1%	23 4.9%	29 6.2%	8 1.7%
No	433 92.9%	417 89.7%	410 88.2%	439 94%
Yes	13 2.8%	31 6.7%	48 10.3%	11 2.4%
No	415 89.1%	402 86.5%	387 83.2%	426 91.2%
Yes	12 2.6%	43 9.2%	46 9.9%	17 3.6%
No	413 88.6%	382 82.2%	382 82.2%	426 91.2%

21. Secondary Outcome

Title	Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no)
Description	Participants who achieved HbA1c less than 7.0 % without severe or blood glucose (BG) confirmed symptomatic hypoglycaemia and without weight gain (yes/no) at weeks 26, 52 and 78 are presented. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia was defined as an episode with plasma glucose value <3.1 mmol/L with symptoms consistent with hypoglycaemia. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame	Week 26, week 52, week 78

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = FAS which comprised all randomised participants. Number Analyzed = number of participants with available data.

Arm/Group Title	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg	Sitagliptin 100 mg
Arm/Group Description	Participants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take sitagliptin 100 mg tablets once daily from week 0 to week 78. In addition, participants were to take oral semaglutide placebo tablets once daily from week 0 to week 78.
Measure Participants	466	465	465	467
Yes	87 18.7%	155 33.3%	208 44.7%	90 19.3%
No	348 74.7%	283 60.9%	228 49%	356 76.2%
Yes	87 18.7%	134 28.8%	195 41.9%	87 18.6%
No	340 73%	297 63.9%	239 51.4%	349 74.7%
Yes	85 18.2%	136 29.2%	151 32.5%	84 18%
No	336 72.1%	288 61.9%	274 58.9%	355 76%

22. Secondary Outcome

Title	Participants Who Achieve HbA1c Reduction ≥1% (10.9 mmol/Mol) and Weight Loss ≥3% (Yes/no)
Description	Participants who achieved HbA1c reduction more than or equal to 1% of their baseline HbA1c and weight loss of more than or equal to 3% of their baseline body weight (yes/no) at weeks 26, 52 and 78 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame	Week 26, week 52, week 78

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = FAS which comprised all randomised participants. Number Analyzed = number of participants with available data.

Arm/Group Title	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg	Sitagliptin 100 mg
Arm/Group Description	Participants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take sitagliptin 100 mg tablets once daily from week 0 to week 78. In addition, participants were to take oral semaglutide placebo tablets once daily from week 0 to week 78.
Measure Participants	466	465	465	467
Yes	55 11.8%	117 25.2%	166 35.7%	43 9.2%
No	380 81.5%	321 69%	270 58.1%	403 86.3%
Yes	73 15.7%	106 22.8%	164 35.3%	51 10.9%
No	354 76%	325 69.9%	270 58.1%	385 82.4%
Yes	76 16.3%	113 24.3%	149 32%	60 12.8%
No	345 74%	311 66.9%	276 59.4%	379 81.2%

23. Secondary Outcome

Title	Time to Additional Anti-diabetic Medication
Description	Presented results are the number of participants who had taken additional anti-diabetic medication anytime during the periods, from week 0 to week 26, week 0 to week 52 and week 0 to week 78. Additional anti-diabetic medication was defined as any new anti-diabetic medication used for more than 21 days with the initiation at or after randomisation (week 0) and before (planned) end-of-treatment (week 78), and/or intensification of anti-diabetic medication (a more than 20% increase in dose relative to baseline) for more than 21 days with the intensification at or after randomisation and before (planned) end-of-treatment. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame	Weeks 0-78

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = FAS which comprised all randomised participants.

Arm/Group Title	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg	Sitagliptin 100 mg
Arm/Group Description	Participants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take sitagliptin 100 mg tablets once daily from week 0 to week 78. In addition, participants were to take oral semaglutide placebo tablets once daily from week 0 to week 78.
Measure Participants	466	465	465	467
Week 0 to week 26	33 7.1%	20 4.3%	15 3.2%	20 4.3%
Week 0 to week 52	137 29.4%	86 18.5%	51 11%	111 23.8%
Week 0 to week 78	179 38.4%	119 25.6%	75 16.1%	148 31.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 3 mg, Sitagliptin 100 mg
	Comments	Time to initiation of additional anti-diabetic medication was analysed using a Cox proportional hazards model with treatment, strata, and region as categorical fixed effects and baseline HbA1c as covariate. Withdrawal for any reason or lost to follow-up contributed to the analysis as events (initiation of additional anti-diabetic medication). Censoring time was one day before planned end of treatment.
	Type of Statistical Test	Superiority
	Comments	This hypothesis was not controlled for multiplicity.
Statistical Test of Hypothesis	p-Value	=0.0063
	Comments	Unadjusted two-sided p-value for test of no difference from 1.
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.34
	Confidence Interval	(2-Sided) 95%; 1.09 to 1.65
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 3 mg / Sitagliptin 100 mg

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 7 mg, Sitagliptin 100 mg
	Comments	Time to initiation of additional anti-diabetic medication was analysed using a Cox proportional hazards model with treatment, strata, and region as categorical fixed effects and baseline HbA1c as covariate. Withdrawal for any reason or lost to follow-up contributed to the analysis as events (initiation of additional anti-diabetic medication). Censoring time was one day before planned end of treatment.
	Type of Statistical Test	Superiority
	Comments	This hypothesis was not controlled for multiplicity.
Statistical Test of Hypothesis	p-Value	=0.0221
	Comments	Unadjusted two-sided p-value for test of no difference from 1.
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.77
	Confidence Interval	(2-Sided) 95%; 0.61 to 0.96
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 7 mg / Sitagliptin 100 mg

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 14 mg, Sitagliptin 100 mg
	Comments	Time to initiation of additional anti-diabetic medication was analysed using a Cox proportional hazards model with treatment, strata, and region as categorical fixed effects and baseline HbA1c as covariate. Withdrawal for any reason or lost to follow-up contributed to the analysis as events (initiation of additional anti-diabetic medication). Censoring time was one day before planned end of treatment.
	Type of Statistical Test	Superiority
	Comments	This hypothesis was not controlled for multiplicity.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Unadjusted two-sided p-value for test of no difference from 1.
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.53
	Confidence Interval	(2-Sided) 95%; 0.41 to 0.68
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 14 mg / Sitagliptin 100 mg

24. Secondary Outcome

Title	Time to Rescue Medication
Description	Presented results are the number of participants who had taken rescue medication anytime during the periods, from week 0 to week 26, week 0 to week 52 and week 0 to week 78. 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 randomisation (week 0) and before last day on trial product, and/or intensification of anti-diabetic medication (a more than 20% increase in dose relative to baseline) for more than 21 days with the intensification at or after randomisation and before last day on trial product. Results are based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was on treatment with trial product, excluding any period after initiation of rescue medication and/or premature trial product discontinuation.
Time Frame	Weeks 0-78

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = FAS which comprised all randomised participants.

Arm/Group Title	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg	Sitagliptin 100 mg
Arm/Group Description	Participants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take sitagliptin 100 mg tablets once daily from week 0 to week 78. In addition, participants were to take oral semaglutide placebo tablets once daily from week 0 to week 78.
Measure Participants	466	465	465	467
Week 0 to week 26	25 5.4%	11 2.4%	5 1.1%	13 2.8%
Week 0 to week 52	121 26%	73 15.7%	31 6.7%	94 20.1%
Week 0 to week 78	160 34.3%	103 22.2%	47 10.1%	129 27.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 3 mg, Sitagliptin 100 mg
	Comments	Time to initiation of rescue medication was analysed using a Cox proportional hazards model with treatment, strata, and region as categorical fixed effects and baseline HbA1c as covariate. Censoring time was one day before last day on trial product.
	Type of Statistical Test	Superiority
	Comments	This hypothesis was not controlled for multiplicity.
Statistical Test of Hypothesis	p-Value	=0.0160
	Comments	Unadjusted two-sided p-value for test of no difference from 1.
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.33
	Confidence Interval	(2-Sided) 95%; 1.05 to 1.68
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 3 mg / Sitagliptin 100 mg

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 7 mg, Sitagliptin 100 mg
	Comments	Time to initiation of rescue medication was analysed using a Cox proportional hazards model with treatment, strata, and region as categorical fixed effects and baseline HbA1c as covariate. Censoring time was one day before last day on trial product.
	Type of Statistical Test	Superiority
	Comments	This hypothesis was not controlled for multiplicity.
Statistical Test of Hypothesis	p-Value	=0.0022
	Comments	Unadjusted two-sided p-value for test of no difference from 1.
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.66
	Confidence Interval	(2-Sided) 95%; 0.51 to 0.86
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 7 mg / Sitagliptin 100 mg

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 14 mg, Sitagliptin 100 mg
	Comments	Time to initiation of rescue medication was analysed using a Cox proportional hazards model with treatment, strata, and region as categorical fixed effects and baseline HbA1c as covariate. Censoring time was one day before last day on trial product.
	Type of Statistical Test	Superiority
	Comments	This hypothesis was not controlled for multiplicity.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Unadjusted two-sided p-value for test of no difference from 1.
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.31
	Confidence Interval	(2-Sided) 95%; 0.22 to 0.43
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 14 mg / Sitagliptin 100 mg

25. Secondary Outcome

Title	Number of TEAEs During Exposure to Trial Product
Description	Treatment emergent adverse events (TEAEs) were recorded from week 0 to week 83 (78-week treatment period plus the 5-week follow-up period). Adverse events (AEs) with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period: Time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.
Time Frame	Weeks 0-83

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = safety analysis set (SAS) which comprised all randomised participants who received at least one dose of trial product.

Arm/Group Title	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg	Sitagliptin 100 mg
Arm/Group Description	Participants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take sitagliptin 100 mg tablets once daily from week 0 to week 78. In addition, participants were to take oral semaglutide placebo tablets once daily from week 0 to week 78.
Measure Participants	466	464	465	466
Number [Events]	1774	1686	1824	1852

26. Secondary Outcome

Title	Change in Amylase (Ratio to Baseline)
Description	Change from baseline (week 0) in amylase (units/litre (U/L)) at weeks 26, 52 and 78 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.
Time Frame	Week 0, week 26, week 52, week 78

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = SAS which comprised all randomised participants who received at least one dose of trial product. Number Analyzed = number of participants with available data.

Arm/Group Title	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg	Sitagliptin 100 mg
Arm/Group Description	Participants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take sitagliptin 100 mg tablets once daily from week 0 to week 78. In addition, participants were to take oral semaglutide placebo tablets once daily from week 0 to week 78.
Measure Participants	466	464	465	466
Week 26	1.03 (25.6)	1.07 (27.5)	1.14 (30.4)	1.08 (21.4)
Week 52	1.03 (25.8)	1.09 (28.8)	1.11 (29.0)	1.08 (24.1)
Week 78	1.02 (28.4)	1.09 (29.2)	1.09 (25.5)	1.08 (25.9)

27. Secondary Outcome

Title	Change in Lipase (Ratio to Baseline)
Description	Change from baseline (week 0) in lipase (U/L) at weeks 26, 52 and 78 is presented as ratio to baseline. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.
Time Frame	Week 0, week 26, week 52, week 78

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = SAS which comprised all randomised participants who received at least one dose of trial product. Number Analyzed = number of participants with available data.

Arm/Group Title	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg	Sitagliptin 100 mg
Arm/Group Description	Participants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take sitagliptin 100 mg tablets once daily from week 0 to week 78. In addition, participants were to take oral semaglutide placebo tablets once daily from week 0 to week 78.
Measure Participants	466	464	465	466
Week 26	1.07 (52.6)	1.13 (60.1)	1.26 (64.9)	1.14 (50.3)
Week 52	1.06 (51.5)	1.15 (59.4)	1.25 (56.6)	1.15 (54.2)
Week 78	1.04 (56.2)	1.14 (61.9)	1.18 (54.3)	1.10 (50.7)

28. Secondary Outcome

Title	Change in Pulse Rate
Description	Change from baseline (week 0) in pulse rate was evaluated at weeks 26, 52 and 78. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.
Time Frame	Week 0, week 26, week 52, week 78

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = SAS which comprised all randomised participants who received at least one dose of trial product. Number Analyzed = number of participants with available data.

Arm/Group Title	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg	Sitagliptin 100 mg
Arm/Group Description	Participants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take sitagliptin 100 mg tablets once daily from week 0 to week 78. In addition, participants were to take oral semaglutide placebo tablets once daily from week 0 to week 78.
Measure Participants	466	464	465	466
Week 26	1 (9)	2 (9)	3 (10)	0 (10)
Week 52	0 (10)	2 (9)	2 (10)	-0 (10)
Week 78	1 (10)	1 (10)	2 (10)	0 (10)

29. Secondary Outcome

Title	Change in SBP and DBP
Description	Change from baseline (week 0) in systolic blood pressure (SBP) and diastolic blood pressure (DBP) was evaluated at weeks 26, 52 and 78. Results are based on the data from the on-treatment observation period which was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.
Time Frame	Week 0, week 26, week 52, week 78

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = SAS which comprised all randomised participants who received at least one dose of trial product. Number Analyzed = number of participants with available data.

Arm/Group Title	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg	Sitagliptin 100 mg
Arm/Group Description	Participants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take sitagliptin 100 mg tablets once daily from week 0 to week 78. In addition, participants were to take oral semaglutide placebo tablets once daily from week 0 to week 78.
Measure Participants	466	464	465	466
SBP: Week 26	-2 (14)	-2 (15)	-3 (14)	-2 (15)
SBP: Week 52	-2 (15)	-4 (14)	-3 (15)	-1 (14)
SBP: Week 78	-2 (15)	-3 (15)	-3 (14)	0 (15)
DBP: Week 26	-1 (9)	-0 (9)	-1 (9)	-0 (9)
DBP: Week 52	-2 (9)	-1 (9)	-1 (9)	-1 (9)
DBP: Week 78	-1 (10)	-1 (10)	-1 (10)	-1 (10)

30. Secondary Outcome

Title	Change in ECG Evaluation
Description	Change from baseline (week 0) in electrocardiogram (ECG) was evaluated at weeks 26, 52 and 78. Change from baseline results are presented as shift in findings (normal, abnormal and not clinically significant (NCS) and abnormal and clinically significant (CS)) from week 0 to week 26, 52 and 78. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame	Week 0, week 26, week 52, week 78

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = SAS which comprised all randomised participants who received at least one dose of trial product. Number Analyzed = number of participants with available data.

Arm/Group Title	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg	Sitagliptin 100 mg
Arm/Group Description	Participants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take sitagliptin 100 mg tablets once daily from week 0 to week 78. In addition, participants were to take oral semaglutide placebo tablets once daily from week 0 to week 78.
Measure Participants	466	464	465	466
Normal (week 0) to normal (week 26)	211 45.3%	214 46%	230 49.5%	204 43.7%
Normal (week 0) to abnormal NCS (week 26)	38 8.2%	42 9%	24 5.2%	41 8.8%
Normal (week 0) to abnormal CS (week 26)	4 0.9%	5 1.1%	0 0%	4 0.9%
Abnormal (week 0) NCS to normal (week 26)	41 8.8%	44 9.5%	42 9%	40 8.6%
Abnormal (week 0) NCS to abnormal NCS (week 26)	132 28.3%	128 27.5%	133 28.6%	143 30.6%
Abnormal (week 0) NCS to abnormal CS (week 26)	4 0.9%	1 0.2%	1 0.2%	3 0.6%
Abnormal (week 0) CS to normal (week 26)	1 0.2%	1 0.2%	0 0%	3 0.6%
Abnormal (week 0) CS to abnormal NCS (week 26)	3 0.6%	2 0.4%	3 0.6%	2 0.4%
Abnormal (week 0) CS to abnormal CS (week 26)	4 0.9%	2 0.4%	6 1.3%	4 0.9%
Normal (week 0) to normal (week 52)	196 42.1%	218 46.9%	219 47.1%	204 43.7%
Normal (week 0) to abnormal NCS (week 52)	47 10.1%	37 8%	33 7.1%	40 8.6%
Normal (week 0) to abnormal CS (week 52)	1 0.2%	0 0%	1 0.2%	4 0.9%
Abnormal (week 0) NCS to normal (week 52)	40 8.6%	49 10.5%	56 12%	48 10.3%
Abnormal (week 0) NCS to abnormal NCS (week 52)	131 28.1%	123 26.5%	118 25.4%	128 27.4%
Abnormal (week 0) NCS to abnormal CS (week 52)	4 0.9%	1 0.2%	0 0%	2 0.4%
Abnormal (week 0) CS to normal (week 52)	1 0.2%	1 0.2%	2 0.4%	1 0.2%
Abnormal (week 0) CS to abnormal NCS (week 52)	3 0.6%	3 0.6%	0 0%	2 0.4%
Abnormal (week 0) CS to abnormal CS (week 52)	4 0.9%	1 0.2%	7 1.5%	6 1.3%
Normal (week 0) to normal (week 78)	196 42.1%	201 43.2%	219 47.1%	208 44.5%
Normal (week 0) to abnormal NCS (week 78)	41 8.8%	43 9.2%	31 6.7%	40 8.6%
Normal (week 0) to abnormal CS (week 78)	3 0.6%	2 0.4%	1 0.2%	1 0.2%
Abnormal (week 0) NCS to normal (week 78)	39 8.4%	45 9.7%	51 11%	47 10.1%
Abnormal (week 0) NCS to abnormal NCS (week 78)	131 28.1%	125 26.9%	114 24.5%	133 28.5%
Abnormal (week 0) NCS to abnormal CS (week 78)	5 1.1%	1 0.2%	3 0.6%	2 0.4%
Abnormal (week 0) CS to normal (week 78)	0 0%	3 0.6%	1 0.2%	3 0.6%
Abnormal (week 0) CS to abnormal NCS (week 78)	4 0.9%	2 0.4%	3 0.6%	2 0.4%
Abnormal (week 0) CS to abnormal CS (week 78)	4 0.9%	1 0.2%	5 1.1%	4 0.9%

31. Secondary Outcome

Title	Change in Physical Examination
Description	Participants with physical examination findings, normal, abnormal NCS and abnormal CS at baseline (weeks -2), weeks 52 and 78 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. Results are presented for the following examinations: 1) Cardiovascular system; 2) Central and peripheral nervous system; 3) Gastrointestinal system, incl. mouth; 4) General appearance; 5) Head, ears, eyes, nose, throat, neck; 6) Lymph node palpation; 7) Musculoskeletal system; 8) Respiratory system; 9) Skin; 10) Thyroid gland.
Time Frame	Week -2, week 52, week 78

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = SAS which comprised all randomised participants who received at least one dose of trial product. Number Analyzed = number of participants with available data.

Arm/Group Title	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg	Sitagliptin 100 mg
Arm/Group Description	Participants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take sitagliptin 100 mg tablets once daily from week 0 to week 78. In addition, participants were to take oral semaglutide placebo tablets once daily from week 0 to week 78.
Measure Participants	466	464	465	466
Normal	431 92.5%	425 91.4%	432 92.9%	424 90.8%
Abnormal NCS	30 6.4%	38 8.2%	30 6.5%	41 8.8%
Abnormal CS	5 1.1%	1 0.2%	3 0.6%	1 0.2%
Normal	398 85.4%	396 85.2%	404 86.9%	399 85.4%
Abnormal NCS	24 5.2%	36 7.7%	28 6%	37 7.9%
Abnormal CS	5 1.1%	1 0.2%	3 0.6%	0 0%
Normal	395 84.8%	386 83%	402 86.5%	399 85.4%
Abnormal NCS	24 5.2%	33 7.1%	24 5.2%	41 8.8%
Abnormal CS	5 1.1%	4 0.9%	2 0.4%	1 0.2%
Normal	410 88%	415 89.2%	407 87.5%	409 87.6%
Abnormal NCS	44 9.4%	42 9%	49 10.5%	43 9.2%
Abnormal CS	12 2.6%	6 1.3%	8 1.7%	14 3%
Normal	376 80.7%	382 82.2%	388 83.4%	385 82.4%
Abnormal NCS	44 9.4%	45 9.7%	38 8.2%	42 9%
Abnormal CS	7 1.5%	6 1.3%	9 1.9%	8 1.7%
Normal	377 80.9%	376 80.9%	384 82.6%	399 85.4%
Abnormal NCS	43 9.2%	43 9.2%	37 8%	37 7.9%
Abnormal CS	4 0.9%	4 0.9%	7 1.5%	5 1.1%
Normal	419 89.9%	421 90.5%	420 90.3%	421 90.1%
Abnormal NCS	45 9.7%	39 8.4%	45 9.7%	45 9.6%
Abnormal CS	2 0.4%	4 0.9%	0 0%	0 0%
Normal	386 82.8%	402 86.5%	397 85.4%	394 84.4%
Abnormal NCS	39 8.4%	28 6%	36 7.7%	40 8.6%
Abnormal CS	1 0.2%	3 0.6%	2 0.4%	2 0.4%
Normal	398 85.4%	387 83.2%	393 84.5%	408 87.4%
Abnormal NCS	26 5.6%	31 6.7%	35 7.5%	31 6.6%
Abnormal CS	0 0%	5 1.1%	0 0%	2 0.4%
Normal	407 87.3%	405 87.1%	412 88.6%	405 86.7%
Abnormal NCS	43 9.2%	45 9.7%	38 8.2%	46 9.9%
Abnormal CS	16 3.4%	14 3%	15 3.2%	15 3.2%
Normal	381 81.8%	384 82.6%	390 83.9%	385 82.4%
Abnormal NCS	37 7.9%	37 8%	33 7.1%	39 8.4%
Abnormal CS	8 1.7%	12 2.6%	12 2.6%	12 2.6%
Normal	379 81.3%	373 80.2%	388 83.4%	394 84.4%
Abnormal NCS	37 7.9%	40 8.6%	28 6%	37 7.9%
Abnormal CS	8 1.7%	10 2.2%	12 2.6%	10 2.1%
Normal	441 94.6%	440 94.6%	435 93.5%	444 95.1%
Abnormal NCS	25 5.4%	24 5.2%	27 5.8%	21 4.5%
Abnormal CS	0 0%	0 0%	3 0.6%	1 0.2%
Normal	398 85.4%	411 88.4%	404 86.9%	410 87.8%
Abnormal NCS	25 5.4%	21 4.5%	27 5.8%	26 5.6%
Abnormal CS	3 0.6%	1 0.2%	4 0.9%	0 0%
Normal	400 85.8%	405 87.1%	399 85.8%	415 88.9%
Abnormal NCS	22 4.7%	17 3.7%	28 6%	25 5.4%
Abnormal CS	2 0.4%	1 0.2%	1 0.2%	1 0.2%
Normal	466 100%	462 99.4%	463 99.6%	464 99.4%
Abnormal NCS	0 0%	1 0.2%	2 0.4%	2 0.4%
Abnormal CS	0 0%	0 0%	0 0%	0 0%
Normal	425 91.2%	432 92.9%	434 93.3%	436 93.4%
Abnormal NCS	1 0.2%	1 0.2%	1 0.2%	0 0%
Abnormal CS	0 0%	0 0%	0 0%	0 0%
Normal	421 90.3%	423 91%	425 91.4%	441 94.4%
Abnormal NCS	2 0.4%	0 0%	3 0.6%	0 0%
Abnormal CS	0 0%	0 0%	0 0%	0 0%
Normal	421 90.3%	435 93.5%	440 94.6%	430 92.1%
Abnormal NCS	39 8.4%	24 5.2%	23 4.9%	32 6.9%
Abnormal CS	6 1.3%	5 1.1%	2 0.4%	4 0.9%
Normal	383 82.2%	400 86%	408 87.7%	403 86.3%
Abnormal NCS	37 7.9%	28 6%	24 5.2%	26 5.6%
Abnormal CS	6 1.3%	5 1.1%	3 0.6%	6 1.3%
Normal	388 83.3%	389 83.7%	402 86.5%	413 88.4%
Abnormal NCS	33 7.1%	31 6.7%	24 5.2%	23 4.9%
Abnormal CS	3 0.6%	3 0.6%	2 0.4%	5 1.1%
Normal	458 98.3%	451 97%	462 99.4%	456 97.6%
Abnormal NCS	6 1.3%	9 1.9%	2 0.4%	10 2.1%
Abnormal CS	2 0.4%	4 0.9%	1 0.2%	0 0%
Normal	418 89.7%	427 91.8%	431 92.7%	429 91.9%
Abnormal NCS	6 1.3%	4 0.9%	3 0.6%	6 1.3%
Abnormal CS	2 0.4%	2 0.4%	1 0.2%	1 0.2%
Normal	419 89.9%	418 89.9%	427 91.8%	434 92.9%
Abnormal NCS	3 0.6%	4 0.9%	1 0.2%	6 1.3%
Abnormal CS	2 0.4%	1 0.2%	0 0%	1 0.2%
Normal	394 84.5%	400 86%	394 84.7%	402 86.1%
Abnormal NCS	66 14.2%	56 12%	61 13.1%	58 12.4%
Abnormal CS	6 1.3%	8 1.7%	10 2.2%	6 1.3%
Normal	372 79.8%	383 82.4%	383 82.4%	375 80.3%
Abnormal NCS	52 11.2%	44 9.5%	44 9.5%	51 10.9%
Abnormal CS	3 0.6%	6 1.3%	8 1.7%	10 2.1%
Normal	361 77.5%	370 79.6%	382 82.2%	393 84.2%
Abnormal NCS	55 11.8%	45 9.7%	38 8.2%	41 8.8%
Abnormal CS	8 1.7%	8 1.7%	8 1.7%	7 1.5%
Normal	451 96.8%	452 97.2%	451 97%	454 97.2%
Abnormal NCS	13 2.8%	11 2.4%	11 2.4%	12 2.6%
Abnormal CS	1 0.2%	1 0.2%	3 0.6%	0 0%
Normal	413 88.6%	423 91%	425 91.4%	427 91.4%
Abnormal NCS	11 2.4%	10 2.2%	7 1.5%	8 1.7%
Abnormal CS	2 0.4%	0 0%	3 0.6%	1 0.2%
Normal	411 88.2%	411 88.4%	418 89.9%	433 92.7%
Abnormal NCS	11 2.4%	12 2.6%	8 1.7%	7 1.5%
Abnormal CS	2 0.4%	0 0%	2 0.4%	1 0.2%

32. Secondary Outcome

Title	Change in Eye Examination Category
Description	Participants with eye examination (fundoscopy) findings, normal, abnormal NCS and abnormal CS at baseline (week -2), week 52 and week 78 are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame	Week -2, week 52, week 78

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = SAS which comprised all randomised participants who received at least one dose of trial product. Number Analyzed = number of participants with available data.

Arm/Group Title	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg	Sitagliptin 100 mg
Arm/Group Description	Participants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take sitagliptin 100 mg tablets once daily from week 0 to week 78. In addition, participants were to take oral semaglutide placebo tablets once daily from week 0 to week 78.
Measure Participants	466	464	465	466
Normal	302 64.8%	299 64.3%	305 65.6%	297 63.6%
Abnormal NCS	130 27.9%	138 29.7%	129 27.7%	137 29.3%
Abnormal CS	27 5.8%	18 3.9%	23 4.9%	29 6.2%
Normal	249 53.4%	253 54.4%	270 58.1%	252 54%
Abnormal NCS	119 25.5%	113 24.3%	101 21.7%	126 27%
Abnormal CS	25 5.4%	22 4.7%	20 4.3%	27 5.8%
Normal	261 56%	255 54.8%	273 58.7%	287 61.5%
Abnormal NCS	135 29%	141 30.3%	130 28%	113 24.2%
Abnormal CS	21 4.5%	19 4.1%	17 3.7%	31 6.6%
Normal	309 66.3%	298 64.1%	308 66.2%	297 63.6%
Abnormal NCS	126 27%	139 29.9%	126 27.1%	138 29.6%
Abnormal CS	24 5.2%	17 3.7%	23 4.9%	28 6%
Normal	247 53%	256 55.1%	271 58.3%	255 54.6%
Abnormal NCS	122 26.2%	112 24.1%	103 22.2%	123 26.3%
Abnormal CS	24 5.2%	20 4.3%	17 3.7%	27 5.8%
Normal	258 55.4%	255 54.8%	275 59.1%	279 59.7%
Abnormal NCS	136 29.2%	146 31.4%	128 27.5%	122 26.1%
Abnormal CS	23 4.9%	14 3%	17 3.7%	30 6.4%

33. Secondary Outcome

Title	Occurrence of Anti-semaglutide Binding Antibodies (Yes/no)
Description	This outcome measure is only applicable for the oral semaglutide treatment arms (3 mg, 7 mg and 14 mg). Number of participants who measured with anti-semaglutide binding antibodies anytime during post-baseline visits (weeks 0-83) are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame	Weeks 0-83

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = number of participants with available data.

Arm/Group Title	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg
Arm/Group Description	Participants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.
Measure Participants	459	460	465
Count of Participants [Participants]	1 0.2%	2 0.4%	3 0.6%

34. Secondary Outcome

Title	Occurrence of Anti-semaglutide Neutralising Antibodies (Yes/no)
Description	This outcome measure is only applicable for the oral semaglutide treatment arms (3 mg, 7 mg and 14 mg). Number of participants who measured with anti-semaglutide neutralising antibodies anytime during post-baseline visits (weeks 0-83) are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame	Weeks 0-83

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = number of participants with available data.

Arm/Group Title	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg
Arm/Group Description	Participants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.
Measure Participants	459	460	465
Count of Participants [Participants]	0 0%	0 0%	0 0%

35. Secondary Outcome

Title	Occurrence of Anti-semaglutide Binding Antibodies Cross Reacting With Native GLP-1 (Yes/no)
Description	This outcome measure is only applicable for the oral semaglutide treatment arms (3 mg, 7 mg and 14 mg). Number of participants who measured with anti-semaglutide binding antibodies cross reacting with native glucagon-like peptide-1 (GLP-1) anytime during post-baseline visits (weeks 0-83) are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame	Weeks 0-83

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = number of participants with available data.

Arm/Group Title	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg
Arm/Group Description	Participants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.
Measure Participants	459	460	465
Count of Participants [Participants]	0 0%	1 0.2%	1 0.2%

36. Secondary Outcome

Title	Occurrence of Anti-semaglutide Neutralising Antibodies Cross Reacting With Native GLP-1 (Yes/no)
Description	This outcome measure is only applicable for the oral semaglutide treatment arms (3 mg, 7 mg and 14 mg). Number of participants who measured with anti-semaglutide neutralising antibodies cross reacting with native GLP-1 anytime during post-baseline visits (weeks 0-83) are presented. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame	Weeks 0-83

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = number of participants with available data.

Arm/Group Title	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg
Arm/Group Description	Participants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.
Measure Participants	459	460	465
Count of Participants [Participants]	0 0%	0 0%	0 0%

37. Secondary Outcome

Title	Anti-semaglutide Binding Antibody Levels
Description	This outcome measure is only applicable for the oral semaglutide treatment arms (3 mg, 7 mg and 14 mg). It is based on the data from participants who were measured with anti-semaglutide antibodies anytime during post-baseline visits (weeks 0-83). Results 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, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame	Weeks 0-83

Outcome Measure Data

Analysis Population Description

Overall number of participants analysed = participants who were found positive for anti-semaglutide antibodies.

Arm/Group Title	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg
Arm/Group Description	Participants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.
Measure Participants	1	2	3
Week 4	9.82 (0)
Week 8	1.93 (0)
Week 14	3.28 (0)
Week 26	2.39 (0)	2.05 (0)
Week 38	2.24 (0)

38. Secondary Outcome

Title	Number of Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes
Description	Treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes were recorded during weeks 0-83 (78-week treatment period plus the 5-week follow-up period). Hypoglycaemic episodes with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the time period when a subject was on treatment with trial product, including any period after initiation of rescue medication. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia: Confirmed by a glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.
Time Frame	Weeks 0-83

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = SAS which comprised all randomised participants who received at least one dose of trial product.

Arm/Group Title	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg	Sitagliptin 100 mg
Arm/Group Description	Participants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take sitagliptin 100 mg tablets once daily from week 0 to week 78. In addition, participants were to take oral semaglutide placebo tablets once daily from week 0 to week 78.
Measure Participants	466	464	465	466
Number [Episodes]	56	42	60	76

39. Secondary Outcome

Title	Participants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes
Description	Treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes were recorded from week 0 to week 83 (78-week treatment period plus the 5-week follow-up period). Hypoglycaemic episodes with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the time period when a subject was on treatment with trial product, including any period after initiation of rescue medication. Severe hypoglycaemia was defined as an episode requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions. BG-confirmed symptomatic hypoglycaemia: Confirmed by a glucose value <3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.
Time Frame	Weeks 0-83

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = SAS which comprised all randomised participants who received at least one dose of trial product.

Arm/Group Title	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg	Sitagliptin 100 mg
Arm/Group Description	Participants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take sitagliptin 100 mg tablets once daily from week 0 to week 78. In addition, participants were to take oral semaglutide placebo tablets once daily from week 0 to week 78.
Measure Participants	466	464	465	466
Count of Participants [Participants]	23 4.9%	24 5.2%	36 7.7%	39 8.4%

40. Secondary Outcome

Title	Semaglutide Plasma Concentration in a Subset of the Participants for Population PK Analyses
Description	This outcome measure is only applicable for the oral semaglutide treatment arms (3 mg, 7 mg and 14 mg). Semaglutide plasma concentrations for participants in the pharmacokinetic (PK) subpopulation are presented. The PK subpopulation consisted of participants from sites in Germany, Japan and the United States receiving oral semaglutide (3 mg, 7 mg or 14 mg). Results are based on the data from the on-treatment observation period and follow-up period. The on-treatment observation period was the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.
Time Frame	Weeks 0-83

Outcome Measure Data

Analysis Population Description

Overall number of participants analysed = number of participants in the PK subpopulation. Number Analyzed = number of participants with available data in the PK subpopulation.

Arm/Group Title	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg
Arm/Group Description	Participants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.
Measure Participants	221	215	205
Week 0	0.4 (0.0)	0.4 (0.0)	0.4 (0.0)
Week 4	1.5 (109.3)	1.5 (102.1)	1.6 (109.1)
Week 8	1.5 (103.9)	4.1 (129.4)	4.2 (128.0)
Week 14	1.4 (111.8)	4.0 (146.8)	9.4 (156.6)
Week 26	1.3 (104.5)	3.7 (122.5)	8.6 (162.2)
Week 38	1.4 (107.8)	3.5 (106.4)	8.6 (163.0)
Week 52	1.4 (105.8)	3.5 (119.0)	8.2 (167.0)
Week 78	1.3 (115.3)	3.5 (127.2)	8.9 (152.7)
Week 83	0.4 (10.3)	0.4 (16.5)	0.4 (42.6)

41. Secondary Outcome

Title	Change in SF-36v2 (Acute Version) Health Survey: Scores From the 8 Domains, the Physical Component Summary (PCS) and the Mental Component Summary (MCS)
Description	SF-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ (acute version) questionnaire measured eight domains of functional health and well-being as well as two component summary scores (physical component summary (PCS) and mental component summary (MCS)). The 0-100 scale scores (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. In the metric of norm-based scores, 50 and 10 corresponds to the mean and standard deviation respectively of the 2009 U.S. general population. Change from baseline (week 0) in the domain scores and component summary (PCS and MCS) scores were evaluated at weeks 26, 52 and 78. A positive change score indicates an improvement since baseline. Results are based on the data from the in-trial observation period.
Time Frame	Week 0, week 26, week 52, week 78

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = FAS which comprised all randomised participants. Number Analyzed = number of participants with available data.

Arm/Group Title	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg	Sitagliptin 100 mg
Arm/Group Description	Participants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take sitagliptin 100 mg tablets once daily from week 0 to week 78. In addition, participants were to take oral semaglutide placebo tablets once daily from week 0 to week 78.
Measure Participants	466	465	465	467
1) Physical functioning (week 26)	0.37 (7.25)	1.12 (6.52)	0.63 (7.13)	0.46 (6.73)
1) Physical functioning (week 52)	0.29 (7.14)	0.64 (7.34)	0.36 (7.30)	0.06 (7.30)
1) Physical functioning (week 78)	0.06 (8.09)	0.94 (6.91)	0.54 (7.98)	0.09 (7.60)
2) Role-Physical (week 26)	0.42 (7.85)	0.76 (7.15)	-0.13 (7.59)	0.38 (8.00)
2) Role-Physical (week 52)	-0.05 (8.40)	-0.06 (9.42)	-0.82 (8.49)	-0.69 (8.08)
2) Role-Physical (week 78)	0.28 (8.14)	-0.01 (8.40)	-0.33 (7.57)	0.44 (7.96)
3) Bodily pain (week 26)	0.56 (9.20)	-0.11 (8.60)	0.22 (9.02)	0.44 (9.18)
3) Bodily pain (week 52)	0.16 (9.44)	-0.65 (9.92)	-0.64 (9.40)	0.67 (8.93)
3) Bodily pain (week 78)	0.48 (9.24)	0.32 (8.85)	0.74 (9.40)	0.54 (9.44)
4) General health (week 26)	1.17 (6.50)	1.67 (6.98)	1.19 (7.00)	1.42 (7.02)
4) General health (week 52)	1.06 (7.07)	1.20 (7.08)	1.03 (6.88)	0.95 (7.38)
4) General health (week 78)	1.02 (7.23)	1.21 (7.60)	1.21 (7.62)	1.32 (7.99)
5) Vitality (week 26)	0.59 (7.28)	1.11 (7.30)	0.88 (7.42)	1.03 (7.42)
5) Vitality (week 52)	0.45 (7.50)	0.79 (8.33)	0.58 (8.15)	0.19 (7.73)
5) Vitality (week 78)	1.05 (8.06)	0.85 (7.92)	0.71 (8.42)	1.07 (8.27)
6) Social functioning (week 26)	0.11 (7.93)	0.15 (8.03)	0.31 (7.33)	0.09 (8.38)
6) Social functioning (week 52)	-0.25 (8.35)	-0.37 (9.39)	-0.83 (8.83)	-0.68 (9.23)
6) Social functioning (week 78)	-0.38 (8.29)	0.19 (8.77)	-0.27 (8.66)	0.57 (8.93)
7) Role emotional (week 26)	0.84 (10.47)	0.67 (9.18)	-0.37 (9.77)	0.15 (9.97)
7) Role emotional (week 52)	0.15 (10.99)	-0.45 (11.89)	-0.86 (10.65)	-0.63 (10.33)
7) Role emotional (week 78)	0.32 (10.98)	0.23 (10.95)	-0.30 (11.00)	-0.24 (10.58)
8) Mental health (week 26)	0.33 (8.32)	0.24 (8.17)	0.24 (8.14)	0.61 (8.03)
8) Mental health (week 52)	0.45 (8.02)	0.42 (9.11)	0.05 (7.99)	0.23 (8.20)
8) Mental health (week 78)	0.19 (9.08)	0.29 (9.33)	0.28 (8.87)	0.30 (9.33)
Physical component summary (week 26)	0.56 (6.42)	0.98 (5.72)	0.63 (6.00)	0.69 (6.24)
Physical component summary (week 52)	0.31 (6.50)	0.36 (6.82)	0.09 (6.47)	0.31 (6.54)
Physical component summary (week 78)	0.46 (6.74)	0.71 (6.24)	0.67 (6.29)	0.70 (6.38)
Mental component summary (week 26)	0.48 (8.62)	0.34 (8.26)	0.08 (8.18)	0.41 (8.16)
Mental component summary (week 52)	0.23 (8.41)	-0.00 (9.43)	-0.37 (8.64)	-0.31 (8.71)
Mental component summary (week 78)	0.27 (9.18)	0.23 (9.50)	-0.07 (9.31)	0.30 (9.46)

42. Secondary Outcome

Title	Change in IWQoL-Lite-CT: Total Score and Scores From the 4 Domains
Description	The Impact of Weight on Quality of Life Clinical Trials Version (IWQOL-Lite-CT) is designed to assess the impact of changes in weight on patients' quality of life within the context of clinical trials. The items of the IWQOL-Lite-CT pertain to physical functioning (physical, physical function and pain/discomfort) and psychosocial domains and all items employ a 5-point graded response scale (never, rarely, sometimes, usually, always; or not at all true, a little true, moderately true, mostly true, completely true). All IWQOL-Lite-CT composite scores range from 0 to 100, with higher scores reflecting better levels of functioning. Results are based on the data from the in-trial observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Time Frame	Week 0, week 26, week 52, week 78

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = FAS which comprised all randomised participants. Number Analyzed = number of participants with available data.

Arm/Group Title	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg	Sitagliptin 100 mg
Arm/Group Description	Participants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take sitagliptin 100 mg tablets once daily from week 0 to week 78. In addition, participants were to take oral semaglutide placebo tablets once daily from week 0 to week 78.
Measure Participants	466	465	465	467
1) Physical (week 26)	3.25 (14.81)	2.38 (14.87)	2.87 (17.32)	1.97 (15.07)
1) Physical (week 52)	1.84 (15.80)	3.03 (16.32)	3.18 (18.40)	1.49 (16.11)
1) Physical (week 78)	2.71 (16.16)	3.55 (16.47)	3.86 (17.37)	2.86 (17.55)
2) Physical function (week 26)	3.52 (16.48)	2.78 (16.13)	3.20 (18.48)	1.70 (16.54)
2) Physical function (week 52)	2.28 (17.00)	3.24 (18.17)	3.19 (19.76)	1.22 (18.21)
2) Physical function (week 78)	2.55 (17.86)	4.04 (17.99)	3.76 (18.78)	2.54 (18.96)
3) Pain/discomfort (week 26)	2.51 (20.28)	1.37 (21.34)	2.03 (22.10)	2.66 (21.27)
3) Pain/discomfort (week 52)	0.76 (22.31)	2.52 (22.04)	3.15 (23.29)	2.12 (21.73)
3) Pain/discomfort (week 78)	3.06 (20.39)	2.35 (22.66)	4.07 (22.28)	3.63 (22.38)
4) Psychosocial (week 26)	2.69 (13.32)	4.30 (15.05)	2.98 (14.86)	2.10 (13.21)
4) Psychosocial (week 52)	3.12 (14.55)	5.19 (15.04)	3.97 (16.46)	2.53 (14.09)
4) Psychosocial (week 78)	3.83 (14.89)	5.36 (15.62)	3.73 (16.22)	3.29 (14.53)
IWQOL-Lite-CT Total (week 26)	2.88 (12.11)	3.62 (13.37)	2.95 (13.87)	2.05 (12.05)
IWQOL-Lite-CT Total (week 52)	2.67 (13.01)	4.43 (13.59)	3.64 (15.22)	2.17 (12.86)
IWQOL-Lite-CT Total (week 78)	3.45 (13.32)	4.73 (14.07)	3.77 (14.97)	3.16 (13.76)

43. Secondary Outcome

Title	Change in CoEQ: Scores From the 4 Domains and the 19 Items
Description	Change from baseline (week 0) in Control of Eating Questionnaire (CoEQ) was evaluated at weeks (wk) 26, 52 and 78. The CoEQ comprised 19 items to assess the intensity and type of food cravings, as well as subjective sensation of appetite and mood, with the 4 domains: 'craving control' (items 9-12, 19), 'positive mood' (items 5-8), 'craving for savoury' (items 4, 16-18) and 'craving for sweet' (items 3, 13-15). The 19 items were scored on an 11-point graded response scale ranging from 10 to 0, with items relating to each of the 4 domains being averaged to create a final score. A low score in the domains 'craving for sweet and 'craving for savoury' represents a low level of craving; whereas a high score in the domains 'craving control' and 'positive mood' represents good control and a good mood, respectively. Results are based on the data from the in-trial observation period.
Time Frame	Week 0, week 26, week 52, week 78

Outcome Measure Data

Analysis Population Description

Overall number of participants analyzed = FAS which comprised all randomised participants. Number Analyzed = number of participants with available data.

Arm/Group Title	Oral Semaglutide 3 mg	Oral Semaglutide 7 mg	Oral Semaglutide 14 mg	Sitagliptin 100 mg
Arm/Group Description	Participants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.	Participants were to take sitagliptin 100 mg tablets once daily from week 0 to week 78. In addition, participants were to take oral semaglutide placebo tablets once daily from week 0 to week 78.
Measure Participants	466	465	465	467
1) Feeling of hunger (wk 26)	-0.41 (2.61)	-0.37 (2.58)	-0.54 (2.58)	-0.18 (2.49)
1) Feeling of hunger (wk 52)	-0.28 (2.50)	-0.23 (2.69)	-0.35 (2.65)	-0.25 (2.39)
1) Feeling of hunger (wk 78)	-0.31 (2.56)	-0.22 (2.73)	-0.36 (2.52)	-0.22 (2.55)
2) Feeling of fullness (wk 26)	-0.08 (2.66)	-0.08 (2.77)	0.15 (2.66)	0.15 (2.45)
2) Feeling of fullness (wk 52)	-0.02 (2.61)	-0.07 (2.64)	0.22 (2.68)	0.27 (2.67)
2) Feeling of fullness (wk 78)	-0.03 (2.59)	-0.09 (2.71)	0.09 (2.74)	0.26 (2.59)
3) Desire to eat sweet foods (wk 26)	-0.41 (2.55)	-0.54 (3.02)	-0.47 (2.98)	-0.33 (2.92)
3) Desire to eat sweet foods (wk 52)	-0.31 (2.74)	-0.31 (2.97)	-0.31 (3.02)	-0.45 (2.75)
3) Desire to eat sweet foods (wk 78)	-0.38 (2.51)	-0.42 (3.02)	-0.45 (2.97)	-0.49 (2.84)
4) Desire to eat savoury foods (wk 26)	-0.27 (2.48)	-0.16 (2.88)	-0.30 (3.03)	-0.35 (2.74)
4) Desire to eat savoury foods (wk 52)	-0.27 (2.78)	-0.21 (2.80)	-0.44 (2.94)	-0.33 (2.70)
4) Desire to eat savoury foods (wk 78)	-0.39 (2.64)	-0.39 (2.95)	-0.39 (2.80)	-0.42 (2.81)
5) Feeling of happiness (wk 26)	0.01 (2.22)	0.03 (2.11)	0.04 (2.22)	0.13 (2.21)
5) Feeling of happiness (wk 52)	0.09 (2.25)	0.04 (2.21)	0.09 (2.15)	0.14 (2.16)
5) Feeling of happiness (wk 78)	-0.05 (2.32)	-0.08 (2.21)	0.04 (2.27)	0.02 (2.47)
6) Feeling of anxiousness (wk 26)	0.02 (2.86)	-0.18 (2.96)	0.20 (3.22)	-0.21 (2.96)
6) Feeling of anxiousness (wk 52)	-0.05 (2.59)	-0.16 (2.97)	-0.06 (3.02)	0.17 (3.14)
6) Feeling of anxiousness (wk 78)	0.05 (2.69)	0.12 (3.22)	-0.12 (2.88)	-0.01 (3.21)
7) Feeling of alertness (wk 26)	0.11 (2.44)	0.03 (2.61)	-0.06 (2.49)	0.05 (2.51)
7) Feeling of alertness (wk 52)	0.01 (2.52)	-0.14 (2.87)	-0.05 (2.50)	-0.05 (2.56)
7) Feeling of alertness (wk 78)	0.10 (2.43)	-0.04 (2.69)	0.04 (2.48)	-0.01 (2.64)
8) Feeling of contentment (wk 26)	0.05 (2.37)	0.04 (2.38)	0.18 (2.37)	0.18 (2.14)
8) Feeling of contentment (wk 52)	0.04 (2.35)	0.08 (2.48)	0.13 (2.40)	0.20 (2.29)
8) Feeling of contentment (wk 78)	-0.04 (2.50)	-0.03 (2.41)	0.17 (2.38)	0.17 (2.39)
9) Food cravings during last 7 days (wk 26)	-0.59 (2.87)	-0.41 (2.94)	-0.37 (2.69)	-0.46 (2.85)
9) Food cravings during last 7 days (wk 52)	-0.40 (2.99)	-0.30 (2.96)	-0.25 (2.86)	-0.21 (3.09)
9) Food cravings during last 7 days (wk 78)	-0.47 (2.87)	-0.28 (2.90)	-0.38 (2.91)	-0.33 (3.05)
10) Strength of food cravings (wk 26)	-0.50 (2.75)	-0.33 (2.93)	-0.25 (2.79)	-0.35 (2.77)
10) Strength of food cravings (wk 52)	-0.23 (2.84)	-0.14 (2.90)	-0.21 (2.74)	-0.30 (2.77)
10) Strength of food cravings (wk 78)	-0.20 (2.89)	-0.28 (2.99)	-0.32 (2.85)	-0.38 (2.79)
11) Difficulty to resist food cravings (wk 26)	-0.46 (2.74)	-0.38 (3.02)	-0.46 (3.04)	-0.17 (2.84)
11) Difficulty to resist food cravings (wk 52)	0.00 (2.79)	-0.23 (3.04)	-0.42 (3.16)	-0.26 (3.04)
11) Difficulty to resist food cravings (wk 78)	-0.04 (3.02)	-0.32 (3.20)	-0.24 (3.14)	-0.22 (2.96)
12) Eating in response to food cravings (wk 26)	-0.40 (2.49)	-0.15 (2.78)	-0.17 (2.78)	-0.27 (2.64)
12) Eating in response to food cravings (wk 52)	-0.04 (2.55)	-0.11 (2.85)	-0.25 (2.73)	-0.17 (2.75)
12) Eating in response to food cravings (wk 78)	-0.02 (2.67)	0.01 (2.76)	-0.17 (2.96)	-0.25 (2.73)
13) Cravings for chocolate (wk 26)	-0.27 (2.69)	-0.03 (2.93)	-0.14 (2.94)	-0.15 (2.78)
13) Cravings for chocolate (wk 52)	-0.28 (2.58)	0.03 (2.93)	0.06 (2.87)	0.03 (2.85)
13) Cravings for chocolate (wk 78)	-0.08 (2.74)	0.00 (2.87)	0.06 (3.01)	0.06 (3.04)
14) Cravings for other sweet foods (wk 26)	-0.33 (2.65)	-0.31 (2.91)	-0.36 (2.82)	-0.33 (2.82)
14) Cravings for other sweet foods (wk 52)	-0.33 (2.79)	-0.34 (2.93)	-0.31 (2.96)	-0.09 (2.90)
14) Cravings for other sweet foods (wk 78)	-0.20 (2.84)	-0.14 (3.01)	-0.40 (2.93)	-0.22 (2.87)
15) Cravings for fruit or fruit juice (wk 26)	-0.20 (3.05)	-0.03 (3.27)	-0.09 (3.04)	-0.07 (3.09)
15) Cravings for fruit or fruit juice (wk 52)	-0.40 (2.99)	-0.01 (3.34)	-0.22 (3.07)	-0.08 (3.02)
15) Cravings for fruit or fruit juice (wk 78)	-0.14 (2.97)	-0.11 (3.51)	-0.02 (3.12)	-0.33 (2.88)
16) Cravings for dairy foods (wk 26)	-0.23 (3.06)	-0.20 (2.90)	-0.37 (3.02)	-0.27 (2.83)
16) Cravings for dairy foods (wk 52)	-0.42 (2.96)	-0.30 (2.97)	-0.41 (2.86)	0.04 (2.89)
16) Cravings for dairy foods (wk 78)	-0.30 (3.00)	-0.20 (2.95)	-0.45 (2.86)	-0.20 (2.81)
17) Cravings for starchy foods (wk 26)	-0.42 (2.65)	-0.24 (2.56)	-0.49 (2.75)	-0.42 (2.86)
17) Cravings for starchy foods (wk 52)	-0.54 (2.86)	-0.35 (2.68)	-0.62 (2.80)	-0.28 (2.68)
17) Cravings for starchy foods (wk 78)	-0.44 (2.94)	-0.32 (2.76)	-0.61 (2.86)	-0.36 (2.72)
18) Cravings for savoury foods (wk 26)	-0.41 (2.74)	-0.16 (2.69)	-0.49 (2.85)	-0.40 (2.70)
18) Cravings for savoury foods (wk 52)	-0.41 (2.85)	-0.20 (2.82)	-0.56 (2.72)	-0.37 (2.73)
18) Cravings for savoury foods (wk 78)	-0.27 (2.88)	-0.16 (2.87)	-0.48 (2.95)	-0.34 (2.60)
19) Difficulty to control eating in general(wk 26)	-0.47 (2.68)	-0.69 (2.77)	-0.49 (2.69)	-0.51 (2.70)
19) Difficulty to control eating in general(wk 52)	-0.32 (2.76)	-0.59 (2.86)	-0.56 (2.75)	-0.51 (2.73)
19) Difficulty to control eating in general(wk 78)	-0.40 (2.71)	-0.59 (2.88)	-0.54 (2.71)	-0.51 (2.81)
Craving control: items 9-12, 19 (wk 26)	0.49 (2.13)	0.39 (2.18)	0.35 (2.16)	0.35 (2.10)
Craving control: items 9-12, 19 (wk 52)	0.20 (2.20)	0.27 (2.26)	0.34 (2.21)	0.29 (2.18)
Craving control: items 9-12, 19 (wk 78)	0.22 (2.30)	0.29 (2.35)	0.33 (2.29)	0.34 (2.19)
Positive mood: items 5-8 (wk 26)	0.04 (1.51)	0.07 (1.43)	-0.01 (1.61)	0.15 (1.47)
Positive mood: items 5-8 (wk 52)	0.04 (1.50)	0.03 (1.54)	0.05 (1.60)	0.03 (1.57)
Positive mood: items 5-8 (wk 78)	-0.01 (1.57)	-0.07 (1.52)	0.09 (1.55)	0.05 (1.74)
Craving for savoury: items 4, 16-18 (wk 26)	-0.33 (1.88)	-0.19 (1.94)	-0.41 (2.07)	-0.36 (1.89)
Craving for savoury: items 4, 16-18 (wk 52)	-0.41 (2.01)	-0.27 (1.95)	-0.51 (2.11)	-0.24 (1.88)
Craving for savoury: items 4, 16-18 (wk 78)	-0.35 (2.06)	-0.26 (2.12)	-0.48 (2.08)	-0.33 (1.93)
Craving for sweet: items 3, 13-15 (wk 26)	-0.30 (1.88)	-0.23 (2.12)	-0.26 (2.10)	-0.22 (2.01)
Craving for sweet: items 3, 13-15 (wk 52)	-0.33 (1.97)	-0.15 (2.17)	-0.19 (2.19)	-0.15 (2.06)
Craving for sweet: items 3, 13-15 (wk 78)	-0.20 (1.94)	-0.16 (2.22)	-0.20 (2.20)	-0.24 (2.06)

Adverse Events

Time Frame	Week 0 to week 83 (78 weeks treatment period + 5 weeks follow-up period). Results are based on the safety analysis set (SAS), which comprised all randomised participants who received at least one dose of trial product.
Adverse Event Reporting Description	Serious adverse events and other AEs were based on the on-treatment observation period, i.e., the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication. All-cause mortality were based on the in-trial observation period, i.e., the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product.
Arm/Group Title	Oral Semaglutide 3 mg		Oral Semaglutide 7 mg		Oral Semaglutide 14 mg		Sitagliptin 100 mg
Arm/Group Description	Participants were to take oral semaglutide 3 mg tablets once daily from week 0 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.		Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4 and 7 mg from week 4 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.		Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 78: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 78. In addition, participants were to take sitagliptin placebo tablets once daily from week 0 to week 78.		Participants were to take sitagliptin 100 mg tablets once daily from week 0 to week 78. In addition, participants were to take oral semaglutide placebo tablets once daily from week 0 to week 78.
All Cause Mortality
	Oral Semaglutide 3 mg		Oral Semaglutide 7 mg		Oral Semaglutide 14 mg		Sitagliptin 100 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/466 (1.1%)		4/464 (0.9%)		1/465 (0.2%)		3/466 (0.6%)
Serious Adverse Events
	Oral Semaglutide 3 mg		Oral Semaglutide 7 mg		Oral Semaglutide 14 mg		Sitagliptin 100 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	64/466 (13.7%)		47/464 (10.1%)		44/465 (9.5%)		58/466 (12.4%)
Blood and lymphatic system disorders
Anaemia	0/466 (0%)	0	1/464 (0.2%)	1	0/465 (0%)	0	0/466 (0%)	0
Iron deficiency anaemia	1/466 (0.2%)	1	0/464 (0%)	0	0/465 (0%)	0	0/466 (0%)	0
Cardiac disorders
Acute coronary syndrome	0/466 (0%)	0	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
Acute left ventricular failure	0/466 (0%)	0	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
Acute myocardial infarction	1/466 (0.2%)	1	1/464 (0.2%)	1	0/465 (0%)	0	1/466 (0.2%)	1
Angina pectoris	1/466 (0.2%)	1	1/464 (0.2%)	1	1/465 (0.2%)	1	0/466 (0%)	0
Angina unstable	3/466 (0.6%)	3	3/464 (0.6%)	3	1/465 (0.2%)	1	2/466 (0.4%)	2
Atrial fibrillation	3/466 (0.6%)	3	2/464 (0.4%)	2	1/465 (0.2%)	1	4/466 (0.9%)	4
Atrial flutter	0/466 (0%)	0	1/464 (0.2%)	1	0/465 (0%)	0	0/466 (0%)	0
Cardiac arrest	1/466 (0.2%)	1	0/464 (0%)	0	0/465 (0%)	0	0/466 (0%)	0
Cardiac failure	1/466 (0.2%)	1	0/464 (0%)	0	0/465 (0%)	0	0/466 (0%)	0
Cardiac failure acute	0/466 (0%)	0	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
Cardiac failure chronic	2/466 (0.4%)	2	0/464 (0%)	0	0/465 (0%)	0	2/466 (0.4%)	3
Cardiac failure congestive	3/466 (0.6%)	3	1/464 (0.2%)	1	2/465 (0.4%)	2	0/466 (0%)	0
Cardio-respiratory arrest	0/466 (0%)	0	1/464 (0.2%)	1	0/465 (0%)	0	0/466 (0%)	0
Congestive cardiomyopathy	0/466 (0%)	0	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
Coronary artery disease	1/466 (0.2%)	1	2/464 (0.4%)	2	1/465 (0.2%)	1	2/466 (0.4%)	2
Coronary artery insufficiency	0/466 (0%)	0	1/464 (0.2%)	1	0/465 (0%)	0	0/466 (0%)	0
Coronary artery stenosis	0/466 (0%)	0	1/464 (0.2%)	1	0/465 (0%)	0	0/466 (0%)	0
Hypertensive heart disease	1/466 (0.2%)	1	0/464 (0%)	0	0/465 (0%)	0	0/466 (0%)	0
Myocardial fibrosis	0/466 (0%)	0	0/464 (0%)	0	1/465 (0.2%)	1	0/466 (0%)	0
Myocardial infarction	2/466 (0.4%)	2	0/464 (0%)	0	1/465 (0.2%)	1	1/466 (0.2%)	1
Supraventricular tachycardia	0/466 (0%)	0	1/464 (0.2%)	1	0/465 (0%)	0	0/466 (0%)	0
Congenital, familial and genetic disorders
Hydrocele	0/466 (0%)	0	1/464 (0.2%)	1	0/465 (0%)	0	0/466 (0%)	0
Ear and labyrinth disorders
Deafness neurosensory	0/466 (0%)	0	0/464 (0%)	0	2/465 (0.4%)	2	0/466 (0%)	0
Exostosis of external ear canal	0/466 (0%)	0	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
Vertigo	0/466 (0%)	0	0/464 (0%)	0	1/465 (0.2%)	1	0/466 (0%)	0
Endocrine disorders
Goitre	1/466 (0.2%)	1	0/464 (0%)	0	0/465 (0%)	0	0/466 (0%)	0
Hypopituitarism	0/466 (0%)	0	0/464 (0%)	0	1/465 (0.2%)	1	0/466 (0%)	0
Eye disorders
Cataract	1/466 (0.2%)	1	0/464 (0%)	0	0/465 (0%)	0	0/466 (0%)	0
Cataract diabetic	1/466 (0.2%)	1	0/464 (0%)	0	0/465 (0%)	0	0/466 (0%)	0
Conjunctival irritation	1/466 (0.2%)	1	0/464 (0%)	0	0/465 (0%)	0	0/466 (0%)	0
Diabetic retinopathy	0/466 (0%)	0	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
Retinal detachment	0/466 (0%)	0	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
Retinal haemorrhage	0/466 (0%)	0	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
Retinopathy proliferative	0/466 (0%)	0	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
Gastrointestinal disorders
Abdominal pain	1/466 (0.2%)	1	0/464 (0%)	0	2/465 (0.4%)	2	1/466 (0.2%)	1
Ascites	1/466 (0.2%)	1	0/464 (0%)	0	0/465 (0%)	0	0/466 (0%)	0
Barrett's oesophagus	0/466 (0%)	0	0/464 (0%)	0	1/465 (0.2%)	1	0/466 (0%)	0
Diarrhoea	1/466 (0.2%)	1	0/464 (0%)	0	1/465 (0.2%)	1	0/466 (0%)	0
Faeces discoloured	0/466 (0%)	0	0/464 (0%)	0	1/465 (0.2%)	1	0/466 (0%)	0
Gastric ulcer	0/466 (0%)	0	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
Gastritis	0/466 (0%)	0	0/464 (0%)	0	1/465 (0.2%)	1	0/466 (0%)	0
Inguinal hernia	0/466 (0%)	0	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
Large intestine polyp	0/466 (0%)	0	1/464 (0.2%)	1	0/465 (0%)	0	0/466 (0%)	0
Mallory-Weiss syndrome	0/466 (0%)	0	1/464 (0.2%)	1	0/465 (0%)	0	0/466 (0%)	0
Nausea	0/466 (0%)	0	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
Pancreatic cyst	0/466 (0%)	0	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
Pancreatitis acute	1/466 (0.2%)	1	0/464 (0%)	0	3/465 (0.6%)	3	0/466 (0%)	0
Vomiting	0/466 (0%)	0	1/464 (0.2%)	1	0/465 (0%)	0	0/466 (0%)	0
General disorders
Complication associated with device	0/466 (0%)	0	1/464 (0.2%)	1	0/465 (0%)	0	0/466 (0%)	0
Fatigue	0/466 (0%)	0	0/464 (0%)	0	1/465 (0.2%)	1	0/466 (0%)	0
Non-cardiac chest pain	1/466 (0.2%)	1	1/464 (0.2%)	1	1/465 (0.2%)	2	1/466 (0.2%)	1
Oedema peripheral	1/466 (0.2%)	1	0/464 (0%)	0	0/465 (0%)	0	0/466 (0%)	0
Polyp	0/466 (0%)	0	0/464 (0%)	0	1/465 (0.2%)	1	0/466 (0%)	0
Pyrexia	2/466 (0.4%)	2	0/464 (0%)	0	0/465 (0%)	0	0/466 (0%)	0
Hepatobiliary disorders
Bile duct stone	1/466 (0.2%)	1	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
Cholecystitis	0/466 (0%)	0	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
Cholecystitis acute	0/466 (0%)	0	1/464 (0.2%)	1	0/465 (0%)	0	3/466 (0.6%)	3
Cholecystitis chronic	1/466 (0.2%)	1	0/464 (0%)	0	2/465 (0.4%)	2	0/466 (0%)	0
Cholelithiasis	0/466 (0%)	0	0/464 (0%)	0	1/465 (0.2%)	1	2/466 (0.4%)	2
Chronic hepatic failure	0/466 (0%)	0	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
Cirrhosis alcoholic	0/466 (0%)	0	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
Hepatic cirrhosis	1/466 (0.2%)	1	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
Hepatitis	0/466 (0%)	0	1/464 (0.2%)	1	0/465 (0%)	0	0/466 (0%)	0
Non-alcoholic steatohepatitis	0/466 (0%)	0	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
Immune system disorders
Sarcoidosis	0/466 (0%)	0	1/464 (0.2%)	1	0/465 (0%)	0	0/466 (0%)	0
Infections and infestations
Abdominal wall abscess	0/466 (0%)	0	1/464 (0.2%)	1	0/465 (0%)	0	0/466 (0%)	0
Appendicitis	0/466 (0%)	0	0/464 (0%)	0	1/465 (0.2%)	1	0/466 (0%)	0
Cellulitis	3/466 (0.6%)	3	0/464 (0%)	0	2/465 (0.4%)	2	1/466 (0.2%)	1
Cholecystitis infective	0/466 (0%)	0	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
Influenza	1/466 (0.2%)	1	1/464 (0.2%)	1	0/465 (0%)	0	0/466 (0%)	0
Neurosyphilis	0/466 (0%)	0	1/464 (0.2%)	1	0/465 (0%)	0	0/466 (0%)	0
Osteomyelitis	1/466 (0.2%)	2	0/464 (0%)	0	0/465 (0%)	0	0/466 (0%)	0
Pelvic abscess	1/466 (0.2%)	1	0/464 (0%)	0	0/465 (0%)	0	0/466 (0%)	0
Peritonitis	0/466 (0%)	0	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
Peritonitis bacterial	2/466 (0.4%)	2	0/464 (0%)	0	0/465 (0%)	0	0/466 (0%)	0
Pneumonia	3/466 (0.6%)	3	1/464 (0.2%)	1	2/465 (0.4%)	2	4/466 (0.9%)	4
Pneumonia klebsiella	0/466 (0%)	0	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
Pyelonephritis	0/466 (0%)	0	1/464 (0.2%)	1	0/465 (0%)	0	2/466 (0.4%)	2
Pyelonephritis acute	1/466 (0.2%)	1	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
Sepsis	1/466 (0.2%)	1	0/464 (0%)	0	1/465 (0.2%)	1	0/466 (0%)	0
Septic phlebitis	0/466 (0%)	0	0/464 (0%)	0	1/465 (0.2%)	1	0/466 (0%)	0
Subcutaneous abscess	0/466 (0%)	0	2/464 (0.4%)	2	0/465 (0%)	0	0/466 (0%)	0
Testicular abscess	0/466 (0%)	0	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
Urinary tract infection	1/466 (0.2%)	1	0/464 (0%)	0	0/465 (0%)	0	0/466 (0%)	0
Urosepsis	0/466 (0%)	0	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
Vestibular neuronitis	1/466 (0.2%)	1	0/464 (0%)	0	0/465 (0%)	0	0/466 (0%)	0
Viral infection	1/466 (0.2%)	1	0/464 (0%)	0	1/465 (0.2%)	1	0/466 (0%)	0
Wound infection staphylococcal	1/466 (0.2%)	1	0/464 (0%)	0	0/465 (0%)	0	0/466 (0%)	0
Injury, poisoning and procedural complications
Cervical vertebral fracture	1/466 (0.2%)	1	0/464 (0%)	0	0/465 (0%)	0	0/466 (0%)	0
Clavicle fracture	0/466 (0%)	0	0/464 (0%)	0	1/465 (0.2%)	1	0/466 (0%)	0
Fall	1/466 (0.2%)	1	0/464 (0%)	0	1/465 (0.2%)	1	0/466 (0%)	0
Incisional hernia	0/466 (0%)	0	0/464 (0%)	0	1/465 (0.2%)	1	0/466 (0%)	0
Incisional hernia, obstructive	0/466 (0%)	0	0/464 (0%)	0	1/465 (0.2%)	1	0/466 (0%)	0
Scapula fracture	0/466 (0%)	0	0/464 (0%)	0	1/465 (0.2%)	2	0/466 (0%)	0
Skull fractured base	0/466 (0%)	0	1/464 (0.2%)	1	0/465 (0%)	0	0/466 (0%)	0
Soft tissue injury	0/466 (0%)	0	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
Subarachnoid haemorrhage	1/466 (0.2%)	1	1/464 (0.2%)	1	0/465 (0%)	0	0/466 (0%)	0
Subdural haematoma	0/466 (0%)	0	2/464 (0.4%)	2	0/465 (0%)	0	0/466 (0%)	0
Ulna fracture	1/466 (0.2%)	1	0/464 (0%)	0	0/465 (0%)	0	0/466 (0%)	0
Upper limb fracture	1/466 (0.2%)	1	0/464 (0%)	0	0/465 (0%)	0	0/466 (0%)	0
Vascular pseudoaneurysm	0/466 (0%)	0	0/464 (0%)	0	1/465 (0.2%)	1	0/466 (0%)	0
Investigations
Liver function test abnormal	0/466 (0%)	0	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
Prostatic specific antigen increased	0/466 (0%)	0	0/464 (0%)	0	1/465 (0.2%)	1	0/466 (0%)	0
Metabolism and nutrition disorders
Diabetes mellitus inadequate control	1/466 (0.2%)	1	1/464 (0.2%)	1	0/465 (0%)	0	1/466 (0.2%)	1
Diabetic metabolic decompensation	0/466 (0%)	0	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
Hyperglycaemia	1/466 (0.2%)	1	0/464 (0%)	0	1/465 (0.2%)	1	0/466 (0%)	0
Hypoglycaemia	0/466 (0%)	0	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/466 (0.2%)	1	1/464 (0.2%)	1	1/465 (0.2%)	2	1/466 (0.2%)	1
Back pain	0/466 (0%)	0	0/464 (0%)	0	1/465 (0.2%)	1	0/466 (0%)	0
Diabetic amyotrophy	0/466 (0%)	0	0/464 (0%)	0	1/465 (0.2%)	1	0/466 (0%)	0
Intervertebral disc protrusion	2/466 (0.4%)	2	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
Lumbar spinal stenosis	0/466 (0%)	0	0/464 (0%)	0	1/465 (0.2%)	1	0/466 (0%)	0
Musculoskeletal chest pain	1/466 (0.2%)	1	0/464 (0%)	0	1/465 (0.2%)	1	0/466 (0%)	0
Neck pain	0/466 (0%)	0	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
Osteoarthritis	3/466 (0.6%)	3	2/464 (0.4%)	2	3/465 (0.6%)	3	2/466 (0.4%)	2
Osteochondrosis	0/466 (0%)	0	1/464 (0.2%)	1	1/465 (0.2%)	1	0/466 (0%)	0
Rotator cuff syndrome	0/466 (0%)	0	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
Spinal osteoarthritis	0/466 (0%)	0	1/464 (0.2%)	1	0/465 (0%)	0	0/466 (0%)	0
Synovitis	0/466 (0%)	0	0/464 (0%)	0	1/465 (0.2%)	1	0/466 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma gastric	0/466 (0%)	0	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
Adenocarcinoma of colon	0/466 (0%)	0	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
B-cell lymphoma	0/466 (0%)	0	1/464 (0.2%)	1	0/465 (0%)	0	0/466 (0%)	0
Brain neoplasm malignant	0/466 (0%)	0	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
Breast cancer	0/466 (0%)	0	0/464 (0%)	0	0/465 (0%)	0	2/466 (0.4%)	2
Breast cancer metastatic	0/466 (0%)	0	1/464 (0.2%)	1	0/465 (0%)	0	0/466 (0%)	0
Colon cancer	0/466 (0%)	0	0/464 (0%)	0	1/465 (0.2%)	1	0/466 (0%)	0
Invasive ductal breast carcinoma	0/466 (0%)	0	1/464 (0.2%)	1	0/465 (0%)	0	0/466 (0%)	0
Nasal cavity cancer	1/466 (0.2%)	1	0/464 (0%)	0	0/465 (0%)	0	0/466 (0%)	0
Ovarian cancer metastatic	1/466 (0.2%)	1	0/464 (0%)	0	0/465 (0%)	0	0/466 (0%)	0
Pancreatic carcinoma metastatic	0/466 (0%)	0	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
Pancreatic neuroendocrine tumour	0/466 (0%)	0	0/464 (0%)	0	1/465 (0.2%)	1	0/466 (0%)	0
Plasma cell myeloma	0/466 (0%)	0	0/464 (0%)	0	1/465 (0.2%)	1	0/466 (0%)	0
Prostate cancer	1/466 (0.2%)	1	1/464 (0.2%)	1	0/465 (0%)	0	0/466 (0%)	0
Rectal adenocarcinoma	0/466 (0%)	0	1/464 (0.2%)	1	0/465 (0%)	0	0/466 (0%)	0
Renal cell carcinoma	0/466 (0%)	0	0/464 (0%)	0	1/465 (0.2%)	1	0/466 (0%)	0
Thyroid cancer	1/466 (0.2%)	1	0/464 (0%)	0	0/465 (0%)	0	0/466 (0%)	0
Uterine leiomyoma	2/466 (0.4%)	2	0/464 (0%)	0	0/465 (0%)	0	0/466 (0%)	0
Nervous system disorders
Brain stem stroke	1/466 (0.2%)	1	0/464 (0%)	0	0/465 (0%)	0	0/466 (0%)	0
Cervicobrachial syndrome	0/466 (0%)	0	1/464 (0.2%)	1	0/465 (0%)	0	0/466 (0%)	0
Chronic inflammatory demyelinating polyradiculoneuropathy	0/466 (0%)	0	0/464 (0%)	0	1/465 (0.2%)	1	0/466 (0%)	0
Encephalopathy	1/466 (0.2%)	1	0/464 (0%)	0	0/465 (0%)	0	0/466 (0%)	0
Facial paralysis	0/466 (0%)	0	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
Focal dyscognitive seizures	0/466 (0%)	0	1/464 (0.2%)	1	0/465 (0%)	0	0/466 (0%)	0
Haemorrhage intracranial	1/466 (0.2%)	1	0/464 (0%)	0	0/465 (0%)	0	0/466 (0%)	0
Haemorrhagic stroke	2/466 (0.4%)	2	0/464 (0%)	0	0/465 (0%)	0	0/466 (0%)	0
Headache	0/466 (0%)	0	0/464 (0%)	0	1/465 (0.2%)	1	0/466 (0%)	0
Ischaemic stroke	3/466 (0.6%)	3	0/464 (0%)	0	2/465 (0.4%)	2	1/466 (0.2%)	1
Neuropathy peripheral	0/466 (0%)	0	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
Sciatica	0/466 (0%)	0	1/464 (0.2%)	1	0/465 (0%)	0	0/466 (0%)	0
Syncope	1/466 (0.2%)	1	0/464 (0%)	0	1/465 (0.2%)	3	1/466 (0.2%)	1
Thalamic infarction	0/466 (0%)	0	1/464 (0.2%)	1	0/465 (0%)	0	0/466 (0%)	0
Transient ischaemic attack	1/466 (0.2%)	1	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
Product Issues
Device dislocation	0/466 (0%)	0	0/464 (0%)	0	1/465 (0.2%)	1	0/466 (0%)	0
Renal and urinary disorders
Acute kidney injury	1/466 (0.2%)	1	0/464 (0%)	0	3/465 (0.6%)	3	0/466 (0%)	0
End stage renal disease	0/466 (0%)	0	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
Haematuria	0/466 (0%)	0	0/464 (0%)	0	1/465 (0.2%)	1	0/466 (0%)	0
Nephrolithiasis	1/466 (0.2%)	1	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
Renal cyst	0/466 (0%)	0	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
Ureterolithiasis	0/466 (0%)	0	0/464 (0%)	0	1/465 (0.2%)	1	0/466 (0%)	0
Reproductive system and breast disorders
Benign prostatic hyperplasia	1/466 (0.2%)	1	0/464 (0%)	0	0/465 (0%)	0	0/466 (0%)	0
Endometrial hyperplasia	1/466 (0.2%)	1	0/464 (0%)	0	0/465 (0%)	0	0/466 (0%)	0
Prostatitis	1/466 (0.2%)	1	0/464 (0%)	0	1/465 (0.2%)	1	0/466 (0%)	0
Uterine polyp	1/466 (0.2%)	1	1/464 (0.2%)	1	0/465 (0%)	0	0/466 (0%)	0
Uterine prolapse	0/466 (0%)	0	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
Respiratory, thoracic and mediastinal disorders
Acute pulmonary oedema	0/466 (0%)	0	0/464 (0%)	0	1/465 (0.2%)	1	0/466 (0%)	0
Acute respiratory distress syndrome	1/466 (0.2%)	1	0/464 (0%)	0	0/465 (0%)	0	0/466 (0%)	0
Acute respiratory failure	1/466 (0.2%)	1	0/464 (0%)	0	1/465 (0.2%)	1	1/466 (0.2%)	1
Asthma	0/466 (0%)	0	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
Chronic obstructive pulmonary disease	0/466 (0%)	0	0/464 (0%)	0	1/465 (0.2%)	1	0/466 (0%)	0
Epistaxis	0/466 (0%)	0	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
Sleep apnoea syndrome	0/466 (0%)	0	1/464 (0.2%)	1	0/465 (0%)	0	0/466 (0%)	0
Skin and subcutaneous tissue disorders
Angioedema	1/466 (0.2%)	1	0/464 (0%)	0	0/465 (0%)	0	0/466 (0%)	0
Surgical and medical procedures
Cataract operation	1/466 (0.2%)	2	0/464 (0%)	0	0/465 (0%)	0	0/466 (0%)	0
Hospitalisation	0/466 (0%)	0	1/464 (0.2%)	1	0/465 (0%)	0	0/466 (0%)	0
Laparoscopic surgery	0/466 (0%)	0	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
Umbilical hernia repair	1/466 (0.2%)	1	0/464 (0%)	0	0/465 (0%)	0	0/466 (0%)	0
Vascular disorders
Deep vein thrombosis	0/466 (0%)	0	0/464 (0%)	0	1/465 (0.2%)	1	0/466 (0%)	0
Essential hypertension	1/466 (0.2%)	1	0/464 (0%)	0	0/465 (0%)	0	0/466 (0%)	0
Hypertension	1/466 (0.2%)	1	1/464 (0.2%)	1	0/465 (0%)	0	0/466 (0%)	0
Hypotension	0/466 (0%)	0	0/464 (0%)	0	0/465 (0%)	0	1/466 (0.2%)	1
Peripheral arterial occlusive disease	1/466 (0.2%)	1	0/464 (0%)	0	0/465 (0%)	0	0/466 (0%)	0
Peripheral artery occlusion	0/466 (0%)	0	0/464 (0%)	0	1/465 (0.2%)	2	0/466 (0%)	0
Thrombosis	0/466 (0%)	0	1/464 (0.2%)	1	0/465 (0%)	0	0/466 (0%)	0
Varicose vein	1/466 (0.2%)	1	1/464 (0.2%)	1	0/465 (0%)	0	0/466 (0%)	0
Other (Not Including Serious) Adverse Events
	Oral Semaglutide 3 mg		Oral Semaglutide 7 mg		Oral Semaglutide 14 mg		Sitagliptin 100 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	222/466 (47.6%)		234/464 (50.4%)		232/465 (49.9%)		239/466 (51.3%)
Eye disorders
Diabetic retinopathy	27/466 (5.8%)	27	24/464 (5.2%)	25	16/465 (3.4%)	16	26/466 (5.6%)	27
Gastrointestinal disorders
Diarrhoea	44/466 (9.4%)	62	53/464 (11.4%)	81	56/465 (12%)	74	37/466 (7.9%)	44
Nausea	34/466 (7.3%)	42	62/464 (13.4%)	74	70/465 (15.1%)	88	31/466 (6.7%)	39
Vomiting	13/466 (2.8%)	15	27/464 (5.8%)	41	42/465 (9%)	82	19/466 (4.1%)	26
Infections and infestations
Influenza	29/466 (6.2%)	35	24/464 (5.2%)	28	18/465 (3.9%)	21	30/466 (6.4%)	35
Nasopharyngitis	53/466 (11.4%)	74	49/464 (10.6%)	65	47/465 (10.1%)	57	47/466 (10.1%)	69
Upper respiratory tract infection	36/466 (7.7%)	53	35/464 (7.5%)	50	26/465 (5.6%)	34	32/466 (6.9%)	49
Urinary tract infection	29/466 (6.2%)	32	21/464 (4.5%)	26	23/465 (4.9%)	30	26/466 (5.6%)	32
Metabolism and nutrition disorders
Decreased appetite	8/466 (1.7%)	8	14/464 (3%)	15	32/465 (6.9%)	32	14/466 (3%)	15
Musculoskeletal and connective tissue disorders
Arthralgia	21/466 (4.5%)	29	13/464 (2.8%)	17	20/465 (4.3%)	25	29/466 (6.2%)	32
Back pain	24/466 (5.2%)	35	25/464 (5.4%)	31	24/465 (5.2%)	25	29/466 (6.2%)	35
Nervous system disorders
Headache	29/466 (6.2%)	37	30/464 (6.5%)	40	36/465 (7.7%)	50	36/466 (7.7%)	57
Vascular disorders
Hypertension	29/466 (6.2%)	32	24/464 (5.2%)	27	26/465 (5.6%)	26	29/466 (6.2%)	29

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.