PIONEER 4: Efficacy and Safety of Oral Semaglutide Versus Liraglutide and Versus Placebo in Subjects With Type 2 Diabetes Mellitus

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02863419
• Collaborator: (none)
• Enrollment: 711
• Locations: 108
• Arms: 3
• Actual Duration (Months): 19.6
• Patients Per Site: 6.6
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This trial is conducted globally. The aim of this trial is to investigate efficacy and safety of oral Semaglutide versus Liraglutide and versus Placebo in Subjects with Type 2 Diabetes Mellitus.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 711 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety of Oral Semaglutide Versus Liraglutide and Versus Placebo in Subjects With Type 2 Diabetes Mellitus
• Actual Study Start Date: Aug 10, 2016
• Actual Primary Completion Date: Aug 19, 2017
• Actual Study Completion Date: Mar 30, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Oral Semaglutide	Drug: semaglutide; Oral semaglutide once-daily.
Active Comparator: Liraglutide	Drug: liraglutide; Subcutaneous (s.c.) injection once-daily.
Placebo Comparator: Placebo	Drug: placebo; Placebo 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 (Week 52) [Week 0, week 52]

   Change from baseline (week 0) in HbA1c was evaluated at 52 weeks. 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 (Week 52) [Week 0, week 52]

   Change from baseline (week 0) in body weight was evaluated at 52 weeks. 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]

   Relative change from baseline (week 0) in body weight (kg) was evaluated at weeks 26 and 52. 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 Fasting Plasma Glucose [Week 0, week 26, week 52]

   Change from baseline (week 0) in fasting plasma glucose (FPG) was evaluated at weeks 26 and 52. 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 Body Mass Index [Week 0, week 26, week 52]

   Change from baseline (week 0) in body mass index (BMI) was evaluated at weeks 26 and 52. 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]

   Change from baseline (week 0) in waist circumference was evaluated at weeks 26 and 52. 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]

   Change from baseline (week 0) in total cholesterol (mmol/L) at weeks 26 and 52 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 Low-density Lipoprotein (LDL) Cholesterol - Ratio to Baseline [Week 0, week 26, week 52]

   Change from baseline (week 0) in low-density lipoprotein (LDL) cholesterol (mmol/L) at weeks 26 and 52 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 Very Low Density Lipoprotein (VLDL) Cholesterol - Ratio to Baseline [Week 0, week 26, week 52]

    Change from baseline (week 0) in VLDL cholesterol (mmol/L) at weeks 26 and 52 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 High-density Lipoprotein (HDL) Cholesterol - Ratio to Baseline [Week 0, week 26, week 52]

    Change from baseline (week 0) in HDL cholesterol (mmol/L) at weeks 26 and 52 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]

    Change from baseline (week 0) in triglycerides (mmol/L) at weeks 26 and 52 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]

    Change from baseline (week 0) in free fatty acids (FFA) (mmol/L) at weeks 26 and 52 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.

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

    Change from baseline (week 0) to week 26 and week 52 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]

    Change from baseline (week 0) in the average of the post-prandial increments over all meals was evaluated at weeks 26 and 52. 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]

    Participants who achieved HbA1c <7.0% (American Diabetes Association (ADA) target) (yes/no), was evaluated at weeks 26 and 52. 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]

    Participants who achieved HbA1c less than or equal to 6.5% (American Association of Clinical Endocrinologists (AACE) target) (yes/no) at weeks 26 and 52 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]

    Participants who achieved weight loss more than or equal to 5% of their baseline body weight (yes/no) at weeks 26 and 52 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]

    Participants who achieved weight loss more than or equal to 10% of their baseline body weight (yes/no) at weeks 26 and 52 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]

    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 and 52 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]

    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 and 52 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 0-52]

    Presented results are the number of participants who had taken additional anti-diabetic medication anytime during the periods, from week 0 to week 26 and week 0 to week 52. 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 52), 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 0-52]

    Presented results are the number of participants who had taken rescue medication anytime during the periods, from week 0 to week 26 and week 0 to week 52. 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 Treatment-emergent Adverse Events (TEAEs) During Exposure to Trial Product [Weeks 0-57]

    Treatment emergent adverse events (TEAEs) were recorded from week 0 to week 57 (52-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]

    Change from baseline (week 0) in amylase (units/litre (U/L)) at weeks 26 and 52 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]

    Change from baseline (week 0) in lipase (U/L) at weeks 26 and 52 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]

    Change from baseline (week 0) in pulse rate was evaluated at weeks 26 and 52. 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]

    Change from baseline (week 0) in systolic blood pressure (SBP) and diastolic blood pressure (DBP) was evaluated at weeks 26 and 52. 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]

    Change from baseline (week 0) in electrocardiogram (ECG) was evaluated at weeks 26 and week 52. 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 and week 52. 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]

    Participants with physical examination findings, normal, abnormal NCS and abnormal CS at baseline (weeks -2) and weeks 52 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]

    Participants with eye examination (fundoscopy) findings, normal, abnormal NCS and abnormal CS at baseline (week -2) and week 52 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 0-57]

    This outcome measure is only applicable for the oral semaglutide 14 mg treatment arm. Number of participants who measured with anti-semaglutide binding antibodies anytime during post-baseline visits (weeks 0-57) 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 0-57]

    This outcome measure is only applicable for the oral semaglutide 14 mg treatment arm. Number of participants who measured with anti-semaglutide neutralising antibodies anytime during post-baseline visits (weeks 0-57) 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) [Week 0-57]

    This outcome measure is only applicable for the oral semaglutide 14 mg treatment arm. 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 0-57) 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 0-57]

    This outcome measure is only applicable for the oral semaglutide 14 mg treatment arm. Number of participants who measured with anti-semaglutide neutralising antibodies cross reacting with native GLP-1 anytime during post-baseline visits (weeks 0-57) 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 0-57]

    This outcome measure is only applicable for the oral semaglutide 14 mg treatment arm. It is based on the data from participants who were measured with anti-semaglutide antibodies anytime during post-baseline visits (weeks 0-57). 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 Blood Glucose-confirmed Symptomatic Hypoglycaemic Episodes [Weeks 0-57]

    Treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes were recorded during weeks 0-57 (52-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 0-57]

    Treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes were recorded from week 0 to week 57 (52-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. Change in DTSQs: Individual Items and Total Treatment Satisfaction Score (6 of the 8 Items Summed) [Week 0, week 26, week 52]

    Change from baseline (week 0) in Diabetes Treatment Satisfaction Questionnaire - status version (DTSQs) was evaluated at week 26 (wk 26) and week 52 (wk 52). The DTSQs items are scored on a 7-point graded response scale ranging from 6 to 0. Higher scores indicate higher levels of treatment satisfaction for DTSQs items 1, 4 -8. For items 2 and 3 a higher score indicates a higher patient perceived experience of hyperglycaemia and hypoglycaemia, respectively. Thus, lower scores indicate a perception of blood glucose levels being "none of the time" unacceptably high (item 2) or low (item 3). The domain score of total treatment satisfaction (total treatment satisfaction score) was computed by adding the six items scores 1, 4-8. The score has a minimum of 0 and a maximum of 36. A higher treatment satisfaction score indicates a higher level of treatment satisfaction.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial

• Male or female, age above or equal to 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 type 2 diabetes mellitus for at least 90 days prior to day of screening.

• HbA1c (glycosylated haemoglobin) of 7.0-9.5 % (53-80.3 mmol/mol) (both inclusive)

• Stable daily dose of metformin (above or equal to 1500 mg or maximum tolerated dose as documented in the subject medical record) alone or in combination with a stable daily dose of a SGLT-2 (sodium-glucose co-transporter-2) inhibitor for at least 90 days prior to day of screening (fixed-dose combinations are allowed)

Exclusion Criteria:

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

• Any disorder, which in the investigator's opinion might jeopardise subject's safety or compliance with the protocol

• 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 and potentially affecting absorption of trial product (e.g. subtotal and total gastrectomy, sleeve gastrectomy, gastric bypass surgery)

• Any of the following: myocardial infarction (MI), stroke or hospitalisation for unstable angina 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

• Subjects with ALT (alanine aminotransferase) above 2.5 × upper normal limit (UNL)

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

• Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria in a period of 90 days before the day of screening. An exception is short-term insulin treatment for acute illness for a total of below or equal to 14 days

• Proliferative retinopathy or maculopathy requiring acute treatment. Verified by fundus photography or dilated fundoscopy performed within 90 days prior to randomisation

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

• History of diabetic ketoacidosis

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Birmingham	Alabama	United States	35222
2	Novo Nordisk Investigational Site	Los Alamitos	California	United States	90720
3	Novo Nordisk Investigational Site	San Diego	California	United States	92111
4	Novo Nordisk Investigational Site	Denver	Colorado	United States	80246
5	Novo Nordisk Investigational Site	Hallandale Beach	Florida	United States	33009
6	Novo Nordisk Investigational Site	Jacksonville	Florida	United States	32256
7	Novo Nordisk Investigational Site	Miami	Florida	United States	33155
8	Novo Nordisk Investigational Site	Ocala	Florida	United States	34470
9	Novo Nordisk Investigational Site	Orlando	Florida	United States	32801
10	Novo Nordisk Investigational Site	Orlando	Florida	United States	32804
11	Novo Nordisk Investigational Site	Ormond Beach	Florida	United States	32174-6302
12	Novo Nordisk Investigational Site	Saint Petersburg	Florida	United States	33713
13	Novo Nordisk Investigational Site	West Palm Beach	Florida	United States	33401
14	Novo Nordisk Investigational Site	Peoria	Illinois	United States	61603
15	Novo Nordisk Investigational Site	Topeka	Kansas	United States	66606
16	Novo Nordisk Investigational Site	Slidell	Louisiana	United States	70461-4231
17	Novo Nordisk Investigational Site	Butte	Montana	United States	59701
18	Novo Nordisk Investigational Site	Lebanon	New Hampshire	United States	03756
19	Novo Nordisk Investigational Site	Teaneck	New Jersey	United States	07666
20	Novo Nordisk Investigational Site	Albany	New York	United States	12203
21	Novo Nordisk Investigational Site	Mineola	New York	United States	11501
22	Novo Nordisk Investigational Site	Greensboro	North Carolina	United States	27408
23	Novo Nordisk Investigational Site	Morganton	North Carolina	United States	28655
24	Novo Nordisk Investigational Site	Wilmington	North Carolina	United States	28401
25	Novo Nordisk Investigational Site	Dublin	Ohio	United States	43016
26	Novo Nordisk Investigational Site	Maumee	Ohio	United States	43537
27	Novo Nordisk Investigational Site	Norman	Oklahoma	United States	73069
28	Novo Nordisk Investigational Site	McMurray	Pennsylvania	United States	15317
29	Novo Nordisk Investigational Site	Summerville	South Carolina	United States	29485
30	Novo Nordisk Investigational Site	Bristol	Tennessee	United States	37620-7352
31	Novo Nordisk Investigational Site	Arlington	Texas	United States	76012-4637
32	Novo Nordisk Investigational Site	Dallas	Texas	United States	75230
33	Novo Nordisk Investigational Site	Dallas	Texas	United States	75390-9302
34	Novo Nordisk Investigational Site	Houston	Texas	United States	77004-7000
35	Novo Nordisk Investigational Site	North Richland Hills	Texas	United States	76180
36	Novo Nordisk Investigational Site	San Antonio	Texas	United States	78229
37	Novo Nordisk Investigational Site	San Antonio	Texas	United States	78249
38	Novo Nordisk Investigational Site	Newport News	Virginia	United States	23606
39	Novo Nordisk Investigational Site	Richmond	Virginia	United States	23219
40	Novo Nordisk Investigational Site	Virginia Beach	Virginia	United States	23454
41	Novo Nordisk Investigational Site	Karlovac		Croatia	47000
42	Novo Nordisk Investigational Site	Osijek		Croatia	31 000
43	Novo Nordisk Investigational Site	Slavonski Brod		Croatia	35 000
44	Novo Nordisk Investigational Site	Zagreb		Croatia	10 000
45	Novo Nordisk Investigational Site	Zagreb		Croatia	10000
46	Novo Nordisk Investigational Site	Nachod		Czechia	54701
47	Novo Nordisk Investigational Site	Plzen		Czechia	304 60
48	Novo Nordisk Investigational Site	Praha 5		Czechia	150 00
49	Novo Nordisk Investigational Site	Bochum		Germany	44791
50	Novo Nordisk Investigational Site	Duisburg		Germany	47051
51	Novo Nordisk Investigational Site	Falkensee		Germany	14612
52	Novo Nordisk Investigational Site	Hamburg		Germany	22607
53	Novo Nordisk Investigational Site	Ludwigshafen		Germany	67059
54	Novo Nordisk Investigational Site	Oldenburg I. Holst		Germany	23758
55	Novo Nordisk Investigational Site	Saint Ingbert-Oberwürzbach		Germany	66386
56	Novo Nordisk Investigational Site	Villingen-Schwenningen		Germany	78048
57	Novo Nordisk Investigational Site	Budapest		Hungary	1032
58	Novo Nordisk Investigational Site	Budapest		Hungary	1042
59	Novo Nordisk Investigational Site	Gyula		Hungary	5700
60	Novo Nordisk Investigational Site	Kalocsa		Hungary	6300
61	Novo Nordisk Investigational Site	Nagykanizsa		Hungary	8800
62	Novo Nordisk Investigational Site	Szeged		Hungary	H-6725
63	Novo Nordisk Investigational Site	Szigetvár		Hungary	7900
64	Novo Nordisk Investigational Site	Szolnok		Hungary	5004
65	Novo Nordisk Investigational Site	Székesfehérvár		Hungary	8000
66	Novo Nordisk Investigational Site	Tatabánya		Hungary	2800
67	Novo Nordisk Investigational Site	Bunkyo-ku, Tokyo		Japan	113-8655
68	Novo Nordisk Investigational Site	Kumamoto-shi,Kumamoto		Japan	862 0976
69	Novo Nordisk Investigational Site	Mito-shi, Ibaraki		Japan	310-0826
70	Novo Nordisk Investigational Site	Okawa-shi, Fukuoka		Japan	831-0016
71	Novo Nordisk Investigational Site	Sapporo-shi, Hokkaido		Japan	060-0001
72	Novo Nordisk Investigational Site	Shimotsuke-shi, Tochigi		Japan	329-0433
73	Novo Nordisk Investigational Site	Suita-shi, Osaka		Japan	564-0051
74	Novo Nordisk Investigational Site	Tochigi		Japan	323-0022
75	Novo Nordisk Investigational Site	Yamato-shi, Kanagawa		Japan	242-0004
76	Novo Nordisk Investigational Site	Ogre		Latvia	LV-5001
77	Novo Nordisk Investigational Site	Riga		Latvia	LV-1002
78	Novo Nordisk Investigational Site	Riga		Latvia	LV-1011
79	Novo Nordisk Investigational Site	Riga		Latvia	LV-1038
80	Novo Nordisk Investigational Site	Bialystok		Poland	15-445
81	Novo Nordisk Investigational Site	Bydgoszcz		Poland	85-822
82	Novo Nordisk Investigational Site	Gdansk		Poland	80-214
83	Novo Nordisk Investigational Site	Gniewkowo		Poland	88-140
84	Novo Nordisk Investigational Site	Krakow		Poland	30-363
85	Novo Nordisk Investigational Site	Poznan		Poland	60-589
86	Novo Nordisk Investigational Site	Szczecin		Poland	70-506
87	Novo Nordisk Investigational Site	Warszawa		Poland	02-507
88	Novo Nordisk Investigational Site	Wroclaw		Poland	52-416
89	Novo Nordisk Investigational Site	Toa Baja		Puerto Rico	00949
90	Novo Nordisk Investigational Site	Bardejov		Slovakia	08501
91	Novo Nordisk Investigational Site	Bratislava		Slovakia	851 01
92	Novo Nordisk Investigational Site	Kosice		Slovakia	040 01
93	Novo Nordisk Investigational Site	Nitra		Slovakia	949 01
94	Novo Nordisk Investigational Site	Roznava		Slovakia	04801
95	Novo Nordisk Investigational Site	Vrutky		Slovakia	038 61
96	Novo Nordisk Investigational Site	Benoni	Gauteng	South Africa	1501
97	Novo Nordisk Investigational Site	Johannesburg	Gauteng	South Africa	2193
98	Novo Nordisk Investigational Site	Durban	KwaZulu-Natal	South Africa	4092
99	Novo Nordisk Investigational Site	Durban	KwaZulu-Natal	South Africa	4450
100	Novo Nordisk Investigational Site	Cape Town	Western Cape	South Africa	7500
101	Novo Nordisk Investigational Site	Kyiv		Ukraine	04114
102	Novo Nordisk Investigational Site	Odesa		Ukraine	65059
103	Novo Nordisk Investigational Site	Vinnytsia		Ukraine	21010
104	Novo Nordisk Investigational Site	Ajman		United Arab Emirates	21499
105	Novo Nordisk Investigational Site	Al Mafraq		United Arab Emirates	2951
106	Novo Nordisk Investigational Site	Dubai		United Arab Emirates	4545
107	Novo Nordisk Investigational Site	Rahba City		United Arab Emirates	34555
108	Novo Nordisk Investigational Site	Umm Al Quwain		United Arab Emirates	24

Sponsors and Collaborators

• Novo Nordisk A/S

Investigators

• Study Director: Global Clinical Registry (GCR, 1452), Novo Nordisk A/S

Study Documents (Full-Text)

• Study Protocol - Oct 29, 2018
• Statistical Analysis Plan - Oct 29, 2018

More Information

Additional Information:

• Clinical Trials at Novo Nordisk

Publications

None provided.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT02863419
• Other Study ID Numbers: NN9924-4224; 2015-005210-30; U1111-1176-6029
• First Posted: Aug 11, 2016
• Last Update Posted: Jul 20, 2022
• Last Verified: Jul 1, 2022

• 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; Liraglutide

Study Results

Participant Flow

Recruitment Details	The trial was conducted at 101 sites in 12 countries as follows:Croatia (5), Czech Republic (3), Germany (8), Hungary (9), Japan (9), Latvia (4), Poland (9), Slovakia (5), South Africa (5), Ukraine (3), United Arab Emirates (2), United States (39).
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 14 mg	Liraglutide 1.8 mg	Placebo
Arm/Group Description	Participants were to take once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose-escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 52). In addition, participants were to take liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take once-daily liraglutide subcutaneous injection (under the skin) for 52 weeks. Participants started liraglutide at 0.6 mg and were dose-escalated in one-week increments until the final maintenance dose of 1.8 mg once-daily was reached (i.e. 0.6 mg from week 0 to week 1, 1.2 mg from week 1 to week 2 and 1.8 mg from week 2 to week 52). In addition, participants were to take oral semaglutide placebo tablets once-daily from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take both oral semaglutide placebo tablets and liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.
Period Title: Overall Study
STARTED	285	284	142
Full Analysis Set (FAS)	285	284	142
Safety Analysis Set (SAS)	285	284	142
COMPLETED	277	274	134
NOT COMPLETED	8	10	8

Baseline Characteristics

Arm/Group Title	Oral Semaglutide 14 mg	Liraglutide 1.8 mg	Placebo	Total
Arm/Group Description	Participants were to take once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose-escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 52). In addition, participants were to take liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take once-daily liraglutide subcutaneous injection (under the skin) for 52 weeks. Participants started liraglutide at 0.6 mg and were dose-escalated in one-week increments until the final maintenance dose of 1.8 mg once-daily was reached (i.e. 0.6 mg from week 0 to week 1, 1.2 mg from week 1 to week 2 and 1.8 mg from week 2 to week 52). In addition, participants were to take oral semaglutide placebo tablets once-daily from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take both oral semaglutide placebo tablets and liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Total of all reporting groups
Overall Participants	285	284	142	711
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	56 (10)	56 (10)	57 (10)	56 (10)
Sex: Female, Male (Count of Participants)
Female	138 48.4%	135 47.5%	68 47.9%	341 48%
Male	147 51.6%	149 52.5%	74 52.1%	370 52%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	17 6%	18 6.3%	5 3.5%	40 5.6%
Not Hispanic or Latino	268 94%	266 93.7%	137 96.5%	671 94.4%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
White	208 73%	212 74.6%	99 69.7%	519 73%
Black or African American	12 4.2%	9 3.2%	8 5.6%	29 4.1%
Asian	39 13.7%	36 12.7%	19 13.4%	94 13.2%
American Indian or Alaska Native	0 0%	1 0.4%	1 0.7%	2 0.3%
Native Hawaiian or Other Pacific Islander	0 0%	1 0.4%	0 0%	1 0.1%
Other	3 1.1%	8 2.8%	3 2.1%	14 2%
Not Applicable	23 8.1%	17 6%	12 8.5%	52 7.3%
Baseline HbA1c (Percentage of HbA1c) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percentage of HbA1c]	8.0 (0.7)	8.0 (0.7)	7.9 (0.7)	8.0 (0.7)

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 14 mg	Liraglutide 1.8 mg	Placebo
Arm/Group Description	Participants were to take once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose-escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 52). In addition, participants were to take liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take once-daily liraglutide subcutaneous injection (under the skin) for 52 weeks. Participants started liraglutide at 0.6 mg and were dose-escalated in one-week increments until the final maintenance dose of 1.8 mg once-daily was reached (i.e. 0.6 mg from week 0 to week 1, 1.2 mg from week 1 to week 2 and 1.8 mg from week 2 to week 52). In addition, participants were to take oral semaglutide placebo tablets once-daily from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take both oral semaglutide placebo tablets and liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.
Measure Participants	285	284	142
In-trial	-1.2 (0.9)	-1.1 (0.9)	-0.1 (0.7)
On-treatment without rescue medication	-1.4 (0.9)	-1.2 (0.9)	-0.1 (0.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 14 mg, Liraglutide 1.8 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 0.4% (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. The non-inferiority margin was 0.4%
	Method	Pattern mixture model
	Comments
Method of Estimation	Estimation Parameter	Mean treatment difference
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.3 to 0.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 14 mg - Liraglutide 1.8 mg

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 14 mg, Liraglutide 1.8 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	0.0645
	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	-0.1
	Confidence Interval	(2-Sided) 95%; -0.3 to 0.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 14 mg - Liraglutide 1.8 mg

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 14 mg, Placebo
	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	-1.1
	Confidence Interval	(2-Sided) 95%; -1.2 to -0.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 14 mg - Placebo

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 14 mg, Liraglutide 1.8 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 0.4%.
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Mean treatment difference
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -0.3 to -0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 14 mg - Liraglutide 1.8 mg

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 14 mg, Liraglutide 1.8 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	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	0.0056
	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%; -0.3 to -0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 14 mg - Liraglutide 1.8 mg

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 14 mg, Placebo
	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	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	-1.2
	Confidence Interval	(2-Sided) 95%; -1.4 to -1.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 14 mg - Placebo

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 14 mg	Liraglutide 1.8 mg	Placebo
Arm/Group Description	Participants were to take once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose-escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 52). In addition, participants were to take liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take once-daily liraglutide subcutaneous injection (under the skin) for 52 weeks. Participants started liraglutide at 0.6 mg and were dose-escalated in one-week increments until the final maintenance dose of 1.8 mg once-daily was reached (i.e. 0.6 mg from week 0 to week 1, 1.2 mg from week 1 to week 2 and 1.8 mg from week 2 to week 52). In addition, participants were to take oral semaglutide placebo tablets once-daily from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take both oral semaglutide placebo tablets and liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.
Measure Participants	285	284	142
In-trial	-4.4 (4.4)	-3.2 (3.7)	-0.6 (3.1)
On-treatment without rescue medication	-4.7 (4.3)	-3.3 (3.7)	-0.7 (3.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 14 mg, Liraglutide 1.8 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	0.0003
	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	-1.2
	Confidence Interval	(2-Sided) 95%; -1.9 to -0.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 14 mg - Liraglutide 1.8 mg

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 14 mg, Placebo
	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	-3.8
	Confidence Interval	(2-Sided) 95%; -4.7 to -3.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 14 mg - Placebo

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 14 mg, Liraglutide 1.8 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%; -2.2 to -0.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 14 mg - Liraglutide 1.8 mg

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 14 mg, Placebo
	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	-4.0
	Confidence Interval	(2-Sided) 95%; -4.8 to -3.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral sema 14 mg - Placebo

3. Secondary Outcome

Title	Change in HbA1c (Week 52)
Description	Change from baseline (week 0) in HbA1c was evaluated at 52 weeks. 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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Oral Semaglutide 14 mg	Liraglutide 1.8 mg	Placebo
Arm/Group Description	Participants were to take once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose-escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 52). In addition, participants were to take liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take once-daily liraglutide subcutaneous injection (under the skin) for 52 weeks. Participants started liraglutide at 0.6 mg and were dose-escalated in one-week increments until the final maintenance dose of 1.8 mg once-daily was reached (i.e. 0.6 mg from week 0 to week 1, 1.2 mg from week 1 to week 2 and 1.8 mg from week 2 to week 52). In addition, participants were to take oral semaglutide placebo tablets once-daily from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take both oral semaglutide placebo tablets and liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.
Measure Participants	275	269	133
Mean (Standard Deviation) [Percentage of HbA1c]	-1.2 (1.0)	-0.9 (1.0)	-0.1 (0.9)

4. Secondary Outcome

Title	Change in Body Weight (Week 52)
Description	Change from baseline (week 0) in body weight was evaluated at 52 weeks. 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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Oral Semaglutide 14 mg	Liraglutide 1.8 mg	Placebo
Arm/Group Description	Participants were to take once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose-escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 52). In addition, participants were to take liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take once-daily liraglutide subcutaneous injection (under the skin) for 52 weeks. Participants started liraglutide at 0.6 mg and were dose-escalated in one-week increments until the final maintenance dose of 1.8 mg once-daily was reached (i.e. 0.6 mg from week 0 to week 1, 1.2 mg from week 1 to week 2 and 1.8 mg from week 2 to week 52). In addition, participants were to take oral semaglutide placebo tablets once-daily from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take both oral semaglutide placebo tablets and liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.
Measure Participants	275	269	133
Mean (Standard Deviation) [Kg]	-4.4 (5.5)	-3.1 (4.4)	-1.0 (3.8)

5. Secondary Outcome

Title	Change in Body Weight (%)
Description	Relative change from baseline (week 0) in body weight (kg) was evaluated at weeks 26 and 52. 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

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 14 mg	Liraglutide 1.8 mg	Placebo
Arm/Group Description	Participants were to take once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose-escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 52). In addition, participants were to take liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take once-daily liraglutide subcutaneous injection (under the skin) for 52 weeks. Participants started liraglutide at 0.6 mg and were dose-escalated in one-week increments until the final maintenance dose of 1.8 mg once-daily was reached (i.e. 0.6 mg from week 0 to week 1, 1.2 mg from week 1 to week 2 and 1.8 mg from week 2 to week 52). In addition, participants were to take oral semaglutide placebo tablets once-daily from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take both oral semaglutide placebo tablets and liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.
Measure Participants	285	284	142
Week 26	-4.89 (4.95)	-3.33 (3.78)	-0.60 (3.34)
Week 52	-4.94 (6.37)	-3.25 (4.33)	-0.99 (4.12)

6. Secondary Outcome

Title	Change in Fasting Plasma Glucose
Description	Change from baseline (week 0) in fasting plasma glucose (FPG) was evaluated at weeks 26 and 52. 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

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 14 mg	Liraglutide 1.8 mg	Placebo
Arm/Group Description	Participants were to take once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose-escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 52). In addition, participants were to take liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take once-daily liraglutide subcutaneous injection (under the skin) for 52 weeks. Participants started liraglutide at 0.6 mg and were dose-escalated in one-week increments until the final maintenance dose of 1.8 mg once-daily was reached (i.e. 0.6 mg from week 0 to week 1, 1.2 mg from week 1 to week 2 and 1.8 mg from week 2 to week 52). In addition, participants were to take oral semaglutide placebo tablets once-daily from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take both oral semaglutide placebo tablets and liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.
Measure Participants	285	284	142
Week 26	-2.04 (2.28)	-1.91 (2.05)	-0.33 (2.03)
Week 52	-1.91 (2.41)	-1.54 (2.41)	-0.66 (1.99)

7. Secondary Outcome

Title	Change in Body Mass Index
Description	Change from baseline (week 0) in body mass index (BMI) was evaluated at weeks 26 and 52. 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

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 14 mg	Liraglutide 1.8 mg	Placebo
Arm/Group Description	Participants were to take once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose-escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 52). In addition, participants were to take liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take once-daily liraglutide subcutaneous injection (under the skin) for 52 weeks. Participants started liraglutide at 0.6 mg and were dose-escalated in one-week increments until the final maintenance dose of 1.8 mg once-daily was reached (i.e. 0.6 mg from week 0 to week 1, 1.2 mg from week 1 to week 2 and 1.8 mg from week 2 to week 52). In addition, participants were to take oral semaglutide placebo tablets once-daily from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take both oral semaglutide placebo tablets and liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.
Measure Participants	285	284	142
Week 26	-1.6 (1.6)	-1.1 (1.3)	-0.2 (1.1)
Week 52	-1.6 (2.0)	-1.1 (1.5)	-0.4 (1.4)

8. Secondary Outcome

Title	Change in Waist Circumference
Description	Change from baseline (week 0) in waist circumference was evaluated at weeks 26 and 52. 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

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 14 mg	Liraglutide 1.8 mg	Placebo
Arm/Group Description	Participants were to take once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose-escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 52). In addition, participants were to take liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take once-daily liraglutide subcutaneous injection (under the skin) for 52 weeks. Participants started liraglutide at 0.6 mg and were dose-escalated in one-week increments until the final maintenance dose of 1.8 mg once-daily was reached (i.e. 0.6 mg from week 0 to week 1, 1.2 mg from week 1 to week 2 and 1.8 mg from week 2 to week 52). In addition, participants were to take oral semaglutide placebo tablets once-daily from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take both oral semaglutide placebo tablets and liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.
Measure Participants	285	284	142
Week 26	-4.2 (5.4)	-3.0 (4.5)	-1.2 (3.9)
Week 52	-4.4 (6.1)	-2.7 (5.1)	-1.7 (4.7)

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 and 52 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

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 14 mg	Liraglutide 1.8 mg	Placebo
Arm/Group Description	Participants were to take once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose-escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 52). In addition, participants were to take liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take once-daily liraglutide subcutaneous injection (under the skin) for 52 weeks. Participants started liraglutide at 0.6 mg and were dose-escalated in one-week increments until the final maintenance dose of 1.8 mg once-daily was reached (i.e. 0.6 mg from week 0 to week 1, 1.2 mg from week 1 to week 2 and 1.8 mg from week 2 to week 52). In addition, participants were to take oral semaglutide placebo tablets once-daily from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take both oral semaglutide placebo tablets and liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.
Measure Participants	285	284	142
Week 26	0.96 (20.3)	0.97 (21.6)	0.99 (17.0)
Week 52	0.98 (20.5)	0.98 (19.6)	1.02 (18.3)

10. Secondary Outcome

Title	Change in Low-density Lipoprotein (LDL) Cholesterol - Ratio to Baseline
Description	Change from baseline (week 0) in low-density lipoprotein (LDL) cholesterol (mmol/L) at weeks 26 and 52 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

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 14 mg	Liraglutide 1.8 mg	Placebo
Arm/Group Description	Participants were to take once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose-escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 52). In addition, participants were to take liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take once-daily liraglutide subcutaneous injection (under the skin) for 52 weeks. Participants started liraglutide at 0.6 mg and were dose-escalated in one-week increments until the final maintenance dose of 1.8 mg once-daily was reached (i.e. 0.6 mg from week 0 to week 1, 1.2 mg from week 1 to week 2 and 1.8 mg from week 2 to week 52). In addition, participants were to take oral semaglutide placebo tablets once-daily from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take both oral semaglutide placebo tablets and liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.
Measure Participants	285	284	142
Week 26	0.95 (29.9)	0.97 (43.6)	0.99 (30.8)
Week 52	0.99 (31.6)	1.00 (38.5)	1.06 (33.1)

11. Secondary Outcome

Title	Change in Very Low Density Lipoprotein (VLDL) Cholesterol - Ratio to Baseline
Description	Change from baseline (week 0) in VLDL cholesterol (mmol/L) at weeks 26 and 52 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

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 14 mg	Liraglutide 1.8 mg	Placebo
Arm/Group Description	Participants were to take once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose-escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 52). In addition, participants were to take liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take once-daily liraglutide subcutaneous injection (under the skin) for 52 weeks. Participants started liraglutide at 0.6 mg and were dose-escalated in one-week increments until the final maintenance dose of 1.8 mg once-daily was reached (i.e. 0.6 mg from week 0 to week 1, 1.2 mg from week 1 to week 2 and 1.8 mg from week 2 to week 52). In addition, participants were to take oral semaglutide placebo tablets once-daily from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take both oral semaglutide placebo tablets and liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.
Measure Participants	285	284	142
Week 26	0.90 (43.5)	0.91 (37.1)	1.02 (29.4)
Week 52	0.87 (41.9)	0.90 (37.5)	0.98 (39.8)

12. Secondary Outcome

Title	Change in High-density Lipoprotein (HDL) Cholesterol - Ratio to Baseline
Description	Change from baseline (week 0) in HDL cholesterol (mmol/L) at weeks 26 and 52 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

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 14 mg	Liraglutide 1.8 mg	Placebo
Arm/Group Description	Participants were to take once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose-escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 52). In addition, participants were to take liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take once-daily liraglutide subcutaneous injection (under the skin) for 52 weeks. Participants started liraglutide at 0.6 mg and were dose-escalated in one-week increments until the final maintenance dose of 1.8 mg once-daily was reached (i.e. 0.6 mg from week 0 to week 1, 1.2 mg from week 1 to week 2 and 1.8 mg from week 2 to week 52). In addition, participants were to take oral semaglutide placebo tablets once-daily from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take both oral semaglutide placebo tablets and liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.
Measure Participants	285	284	142
Week 26	1.02 (13.8)	1.02 (15.2)	1.02 (12.2)
Week 52	1.03 (13.8)	1.01 (14.7)	1.00 (12.7)

13. Secondary Outcome

Title	Change in Triglycerides - Ratio to Baseline
Description	Change from baseline (week 0) in triglycerides (mmol/L) at weeks 26 and 52 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

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 14 mg	Liraglutide 1.8 mg	Placebo
Arm/Group Description	Participants were to take once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose-escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 52). In addition, participants were to take liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take once-daily liraglutide subcutaneous injection (under the skin) for 52 weeks. Participants started liraglutide at 0.6 mg and were dose-escalated in one-week increments until the final maintenance dose of 1.8 mg once-daily was reached (i.e. 0.6 mg from week 0 to week 1, 1.2 mg from week 1 to week 2 and 1.8 mg from week 2 to week 52). In addition, participants were to take oral semaglutide placebo tablets once-daily from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take both oral semaglutide placebo tablets and liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.
Measure Participants	285	284	142
Week 26	0.89 (48.4)	0.91 (38.3)	1.01 (34.7)
Week 52	0.87 (47.0)	0.89 (41.1)	0.97 (43.4)

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 and 52 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

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 14 mg	Liraglutide 1.8 mg	Placebo
Arm/Group Description	Participants were to take once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose-escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 52). In addition, participants were to take liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take once-daily liraglutide subcutaneous injection (under the skin) for 52 weeks. Participants started liraglutide at 0.6 mg and were dose-escalated in one-week increments until the final maintenance dose of 1.8 mg once-daily was reached (i.e. 0.6 mg from week 0 to week 1, 1.2 mg from week 1 to week 2 and 1.8 mg from week 2 to week 52). In addition, participants were to take oral semaglutide placebo tablets once-daily from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take both oral semaglutide placebo tablets and liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.
Measure Participants	285	284	142
Week 26	0.94 (48.0)	0.95 (50.7)	1.06 (49.1)
Week 52	0.83 (49.3)	0.87 (51.2)	0.89 (46.8)

15. Secondary Outcome

Title	Change in SMPG - Mean 7-point Profile
Description	Change from baseline (week 0) to week 26 and week 52 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

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 14 mg	Liraglutide 1.8 mg	Placebo
Arm/Group Description	Participants were to take once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose-escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 52). In addition, participants were to take liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take once-daily liraglutide subcutaneous injection (under the skin) for 52 weeks. Participants started liraglutide at 0.6 mg and were dose-escalated in one-week increments until the final maintenance dose of 1.8 mg once-daily was reached (i.e. 0.6 mg from week 0 to week 1, 1.2 mg from week 1 to week 2 and 1.8 mg from week 2 to week 52). In addition, participants were to take oral semaglutide placebo tablets once-daily from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take both oral semaglutide placebo tablets and liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.
Measure Participants	285	284	142
Week 26	-2.2 (2.3)	-2.0 (2.0)	-0.7 (1.8)
Week 52	-2.2 (2.3)	-1.8 (2.2)	-0.9 (1.7)

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 and 52. 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

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 14 mg	Liraglutide 1.8 mg	Placebo
Arm/Group Description	Participants were to take once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose-escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 52). In addition, participants were to take liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take once-daily liraglutide subcutaneous injection (under the skin) for 52 weeks. Participants started liraglutide at 0.6 mg and were dose-escalated in one-week increments until the final maintenance dose of 1.8 mg once-daily was reached (i.e. 0.6 mg from week 0 to week 1, 1.2 mg from week 1 to week 2 and 1.8 mg from week 2 to week 52). In addition, participants were to take oral semaglutide placebo tablets once-daily from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take both oral semaglutide placebo tablets and liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.
Measure Participants	285	284	142
Week 26	-0.7 (1.9)	-0.4 (2.0)	-0.2 (1.9)
Week 52	-0.5 (1.9)	-0.5 (2.1)	-0.4 (1.9)

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 and 52. 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

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 14 mg	Liraglutide 1.8 mg	Placebo
Arm/Group Description	Participants were to take once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose-escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 52). In addition, participants were to take liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take once-daily liraglutide subcutaneous injection (under the skin) for 52 weeks. Participants started liraglutide at 0.6 mg and were dose-escalated in one-week increments until the final maintenance dose of 1.8 mg once-daily was reached (i.e. 0.6 mg from week 0 to week 1, 1.2 mg from week 1 to week 2 and 1.8 mg from week 2 to week 52). In addition, participants were to take oral semaglutide placebo tablets once-daily from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take both oral semaglutide placebo tablets and liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.
Measure Participants	285	284	142
Yes	188 66%	168 59.2%	19 13.4%
No	90 31.6%	104 36.6%	115 81%
Yes	167 58.6%	148 52.1%	20 14.1%
No	108 37.9%	121 42.6%	113 79.6%

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 and 52 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

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 14 mg	Liraglutide 1.8 mg	Placebo
Arm/Group Description	Participants were to take once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose-escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 52). In addition, participants were to take liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take once-daily liraglutide subcutaneous injection (under the skin) for 52 weeks. Participants started liraglutide at 0.6 mg and were dose-escalated in one-week increments until the final maintenance dose of 1.8 mg once-daily was reached (i.e. 0.6 mg from week 0 to week 1, 1.2 mg from week 1 to week 2 and 1.8 mg from week 2 to week 52). In addition, participants were to take oral semaglutide placebo tablets once-daily from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take both oral semaglutide placebo tablets and liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.
Measure Participants	285	284	142
Yes	133 46.7%	116 40.8%	7 4.9%
No	145 50.9%	156 54.9%	127 89.4%
Yes	119 41.8%	88 31%	5 3.5%
No	156 54.7%	181 63.7%	128 90.1%

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 and 52 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

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 14 mg	Liraglutide 1.8 mg	Placebo
Arm/Group Description	Participants were to take once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose-escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 52). In addition, participants were to take liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take once-daily liraglutide subcutaneous injection (under the skin) for 52 weeks. Participants started liraglutide at 0.6 mg and were dose-escalated in one-week increments until the final maintenance dose of 1.8 mg once-daily was reached (i.e. 0.6 mg from week 0 to week 1, 1.2 mg from week 1 to week 2 and 1.8 mg from week 2 to week 52). In addition, participants were to take oral semaglutide placebo tablets once-daily from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take both oral semaglutide placebo tablets and liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.
Measure Participants	285	284	142
Yes	121 42.5%	75 26.4%	10 7%
No	157 55.1%	196 69%	124 87.3%
Yes	123 43.2%	66 23.2%	16 11.3%
No	152 53.3%	203 71.5%	117 82.4%

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 and 52 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

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 14 mg	Liraglutide 1.8 mg	Placebo
Arm/Group Description	Participants were to take once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose-escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 52). In addition, participants were to take liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take once-daily liraglutide subcutaneous injection (under the skin) for 52 weeks. Participants started liraglutide at 0.6 mg and were dose-escalated in one-week increments until the final maintenance dose of 1.8 mg once-daily was reached (i.e. 0.6 mg from week 0 to week 1, 1.2 mg from week 1 to week 2 and 1.8 mg from week 2 to week 52). In addition, participants were to take oral semaglutide placebo tablets once-daily from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take both oral semaglutide placebo tablets and liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.
Measure Participants	285	284	142
Yes	39 13.7%	16 5.6%	0 0%
No	239 83.9%	255 89.8%	134 94.4%
Yes	45 15.8%	20 7%	4 2.8%
No	230 80.7%	249 87.7%	129 90.8%

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 and 52 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

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 14 mg	Liraglutide 1.8 mg	Placebo
Arm/Group Description	Participants were to take once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose-escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 52). In addition, participants were to take liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take once-daily liraglutide subcutaneous injection (under the skin) for 52 weeks. Participants started liraglutide at 0.6 mg and were dose-escalated in one-week increments until the final maintenance dose of 1.8 mg once-daily was reached (i.e. 0.6 mg from week 0 to week 1, 1.2 mg from week 1 to week 2 and 1.8 mg from week 2 to week 52). In addition, participants were to take oral semaglutide placebo tablets once-daily from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take both oral semaglutide placebo tablets and liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.
Measure Participants	285	284	142
Yes	169 59.3%	145 51.1%	15 10.6%
No	109 38.2%	126 44.4%	119 83.8%
Yes	155 54.4%	130 45.8%	15 10.6%
No	120 42.1%	139 48.9%	118 83.1%

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 and 52 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

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 14 mg	Liraglutide 1.8 mg	Placebo
Arm/Group Description	Participants were to take once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose-escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 52). In addition, participants were to take liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take once-daily liraglutide subcutaneous injection (under the skin) for 52 weeks. Participants started liraglutide at 0.6 mg and were dose-escalated in one-week increments until the final maintenance dose of 1.8 mg once-daily was reached (i.e. 0.6 mg from week 0 to week 1, 1.2 mg from week 1 to week 2 and 1.8 mg from week 2 to week 52). In addition, participants were to take oral semaglutide placebo tablets once-daily from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take both oral semaglutide placebo tablets and liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.
Measure Participants	285	284	142
Yes	130 45.6%	93 32.7%	5 3.5%
No	148 51.9%	178 62.7%	129 90.8%
Yes	120 42.1%	77 27.1%	9 6.3%
No	155 54.4%	192 67.6%	124 87.3%

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 and week 0 to week 52. 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 52), 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 0-52

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Oral Semaglutide 14 mg	Liraglutide 1.8 mg	Placebo
Arm/Group Description	Participants were to take once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose-escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 52). In addition, participants were to take liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take once-daily liraglutide subcutaneous injection (under the skin) for 52 weeks. Participants started liraglutide at 0.6 mg and were dose-escalated in one-week increments until the final maintenance dose of 1.8 mg once-daily was reached (i.e. 0.6 mg from week 0 to week 1, 1.2 mg from week 1 to week 2 and 1.8 mg from week 2 to week 52). In addition, participants were to take oral semaglutide placebo tablets once-daily from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take both oral semaglutide placebo tablets and liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.
Measure Participants	285	284	142
Week 0 to week 26	20 7%	16 5.6%	12 8.5%
Week 0 to week 52	39 13.7%	29 10.2%	46 32.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 14 mg, Liraglutide 1.8 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	0.4915
	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	1.17
	Confidence Interval	(2-Sided) 95%; 0.75 to 1.80
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 14 mg / Liraglutide 1.8 mg

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 14 mg, Placebo
	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	0.32
	Confidence Interval	(2-Sided) 95%; 0.21 to 0.48
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 14 mg / Placebo

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 and week 0 to week 52. 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 0-52

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Oral Semaglutide 14 mg	Liraglutide 1.8 mg	Placebo
Arm/Group Description	Participants were to take once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose-escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 52). In addition, participants were to take liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take once-daily liraglutide subcutaneous injection (under the skin) for 52 weeks. Participants started liraglutide at 0.6 mg and were dose-escalated in one-week increments until the final maintenance dose of 1.8 mg once-daily was reached (i.e. 0.6 mg from week 0 to week 1, 1.2 mg from week 1 to week 2 and 1.8 mg from week 2 to week 52). In addition, participants were to take oral semaglutide placebo tablets once-daily from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take both oral semaglutide placebo tablets and liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.
Measure Participants	285	284	142
Week 0 - week 26	10 3.5%	9 3.2%	11 7.7%
Week 0 - week 52	20 7%	18 6.3%	43 30.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 14 mg, Liraglutide 1.8 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	0.6252
	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	1.17
	Confidence Interval	(2-Sided) 95%; 0.62 to 2.22
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 14 mg / Liraglutide 1.8 mg

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Oral Semaglutide 14 mg, Placebo
	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	0.15
	Confidence Interval	(2-Sided) 95%; 0.09 to 0.26
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 14 mg / Placebo

25. Secondary Outcome

Title	Number of Treatment-emergent Adverse Events (TEAEs) During Exposure to Trial Product
Description	Treatment emergent adverse events (TEAEs) were recorded from week 0 to week 57 (52-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 0-57

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 14 mg	Liraglutide 1.8 mg	Placebo
Arm/Group Description	Participants were to take once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose-escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 52). In addition, participants were to take liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take once-daily liraglutide subcutaneous injection (under the skin) for 52 weeks. Participants started liraglutide at 0.6 mg and were dose-escalated in one-week increments until the final maintenance dose of 1.8 mg once-daily was reached (i.e. 0.6 mg from week 0 to week 1, 1.2 mg from week 1 to week 2 and 1.8 mg from week 2 to week 52). In addition, participants were to take oral semaglutide placebo tablets once-daily from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take both oral semaglutide placebo tablets and liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.
Measure Participants	285	284	142
Number [Events]	973	927	300

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 and 52 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

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 14 mg	Liraglutide 1.8 mg	Placebo
Arm/Group Description	Participants were to take once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose-escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 52). In addition, participants were to take liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take once-daily liraglutide subcutaneous injection (under the skin) for 52 weeks. Participants started liraglutide at 0.6 mg and were dose-escalated in one-week increments until the final maintenance dose of 1.8 mg once-daily was reached (i.e. 0.6 mg from week 0 to week 1, 1.2 mg from week 1 to week 2 and 1.8 mg from week 2 to week 52). In addition, participants were to take oral semaglutide placebo tablets once-daily from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take both oral semaglutide placebo tablets and liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.
Measure Participants	285	284	142
Week 26	1.13 (24.9)	1.11 (26.1)	0.99 (23.1)
Week 52	1.14 (27.4)	1.10 (26.1)	0.98 (21.9)

27. Secondary Outcome

Title	Change in Lipase - Ratio to Baseline
Description	Change from baseline (week 0) in lipase (U/L) at weeks 26 and 52 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

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 14 mg	Liraglutide 1.8 mg	Placebo
Arm/Group Description	Participants were to take once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose-escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 52). In addition, participants were to take liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take once-daily liraglutide subcutaneous injection (under the skin) for 52 weeks. Participants started liraglutide at 0.6 mg and were dose-escalated in one-week increments until the final maintenance dose of 1.8 mg once-daily was reached (i.e. 0.6 mg from week 0 to week 1, 1.2 mg from week 1 to week 2 and 1.8 mg from week 2 to week 52). In addition, participants were to take oral semaglutide placebo tablets once-daily from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take both oral semaglutide placebo tablets and liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.
Measure Participants	285	284	142
Week 26	1.33 (53.3)	1.40 (58.8)	0.99 (45.7)
Week 52	1.28 (59.3)	1.32 (51.5)	0.96 (44.2)

28. Secondary Outcome

Title	Change in Pulse Rate
Description	Change from baseline (week 0) in pulse rate was evaluated at weeks 26 and 52. 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

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 14 mg	Liraglutide 1.8 mg	Placebo
Arm/Group Description	Participants were to take once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose-escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 52). In addition, participants were to take liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take once-daily liraglutide subcutaneous injection (under the skin) for 52 weeks. Participants started liraglutide at 0.6 mg and were dose-escalated in one-week increments until the final maintenance dose of 1.8 mg once-daily was reached (i.e. 0.6 mg from week 0 to week 1, 1.2 mg from week 1 to week 2 and 1.8 mg from week 2 to week 52). In addition, participants were to take oral semaglutide placebo tablets once-daily from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take both oral semaglutide placebo tablets and liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.
Measure Participants	285	284	142
Week 26	2 (9)	3 (11)	0 (9)
Week 52	2 (9)	3 (9)	0 (9)

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 and 52. 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

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 14 mg	Liraglutide 1.8 mg	Placebo
Arm/Group Description	Participants were to take once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose-escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 52). In addition, participants were to take liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take once-daily liraglutide subcutaneous injection (under the skin) for 52 weeks. Participants started liraglutide at 0.6 mg and were dose-escalated in one-week increments until the final maintenance dose of 1.8 mg once-daily was reached (i.e. 0.6 mg from week 0 to week 1, 1.2 mg from week 1 to week 2 and 1.8 mg from week 2 to week 52). In addition, participants were to take oral semaglutide placebo tablets once-daily from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take both oral semaglutide placebo tablets and liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.
Measure Participants	285	284	142
SBP: 26 weeks	-4 (13)	-4 (13)	-2 (13)
SBP: 52 weeks	-3 (14)	-3 (13)	-0 (13)
DBP: 26 weeks	-1 (9)	-0 (9)	-1 (9)
DBP: 52 weeks	-1 (8)	-1 (9)	0 (9)

30. Secondary Outcome

Title	Change in ECG Evaluation
Description	Change from baseline (week 0) in electrocardiogram (ECG) was evaluated at weeks 26 and week 52. 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 and week 52. 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

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 14 mg	Liraglutide 1.8 mg	Placebo
Arm/Group Description	Participants were to take once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose-escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 52). In addition, participants were to take liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take once-daily liraglutide subcutaneous injection (under the skin) for 52 weeks. Participants started liraglutide at 0.6 mg and were dose-escalated in one-week increments until the final maintenance dose of 1.8 mg once-daily was reached (i.e. 0.6 mg from week 0 to week 1, 1.2 mg from week 1 to week 2 and 1.8 mg from week 2 to week 52). In addition, participants were to take oral semaglutide placebo tablets once-daily from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take both oral semaglutide placebo tablets and liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.
Measure Participants	285	284	142
Normal (week 0) to normal (week 26)	130 45.6%	123 43.3%	67 47.2%
Normal (week 0) to abnormal NCS (week 26)	19 6.7%	20 7%	6 4.2%
Normal (week 0) to abnormal CS (week 26)	0 0%	0 0%	0 0%
Abnormal NCS (week 0) to normal (week 26)	15 5.3%	27 9.5%	19 13.4%
Abnormal NCS (week 0) to abnormal NCS (week 26)	81 28.4%	75 26.4%	33 23.2%
Abnormal NCS (week 0) to abnormal CS (week 26)	0 0%	0 0%	0 0%
Abnormal CS (week 0) to normal (week 26)	0 0%	2 0.7%	2 1.4%
Abnormal CS (week 0) to abnormal NCS (week 26)	2 0.7%	2 0.7%	1 0.7%
Abnormal CS (week 0) to abnormal CS (week 26)	3 1.1%	7 2.5%	0 0%
Normal (week 0) to Normal (week 52)	113 39.6%	123 43.3%	64 45.1%
Normal (week 0) to Abnormal NCS (week 52)	31 10.9%	14 4.9%	5 3.5%
Normal (week 0) to Abnormal CS (week 52)	1 0.4%	1 0.4%	1 0.7%
Abnormal NCS (week 0) to Normal (week 52)	19 6.7%	26 9.2%	14 9.9%
Abnormal NCS (week 0) to Abnormal NCS (week 52)	73 25.6%	73 25.7%	37 26.1%
Abnormal NCS (week 0) to Abnormal CS (week 52)	0 0%	0 0%	0 0%
Abnormal CS (week 0) to Normal (week 52)	0 0%	3 1.1%	2 1.4%
Abnormal CS (week 0) to Abnormal NCS (week 52)	1 0.4%	1 0.4%	1 0.7%
Abnormal CS (week 0) to Abnormal CS (week 52)	3 1.1%	5 1.8%	0 0%

31. Secondary Outcome

Title	Change in Physical Examination
Description	Participants with physical examination findings, normal, abnormal NCS and abnormal CS at baseline (weeks -2) and weeks 52 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

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 14 mg	Liraglutide 1.8 mg	Placebo
Arm/Group Description	Participants were to take once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose-escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 52). In addition, participants were to take liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take once-daily liraglutide subcutaneous injection (under the skin) for 52 weeks. Participants started liraglutide at 0.6 mg and were dose-escalated in one-week increments until the final maintenance dose of 1.8 mg once-daily was reached (i.e. 0.6 mg from week 0 to week 1, 1.2 mg from week 1 to week 2 and 1.8 mg from week 2 to week 52). In addition, participants were to take oral semaglutide placebo tablets once-daily from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take both oral semaglutide placebo tablets and liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.
Measure Participants	285	284	142
Normal	260 91.2%	249 87.7%	128 90.1%
Abnormal NCS	23 8.1%	26 9.2%	12 8.5%
Abnormal CS	2 0.7%	9 3.2%	2 1.4%
Normal	255 89.5%	236 83.1%	118 83.1%
Abnormal NCS	19 6.7%	24 8.5%	15 10.6%
Abnormal CS	1 0.4%	9 3.2%	0 0%
Normal	258 90.5%	254 89.4%	123 86.6%
Abnormal NCS	16 5.6%	16 5.6%	13 9.2%
Abnormal CS	11 3.9%	14 4.9%	6 4.2%
Normal	247 86.7%	239 84.2%	115 81%
Abnormal NCS	20 7%	20 7%	11 7.7%
Abnormal CS	8 2.8%	10 3.5%	7 4.9%
Normal	275 96.5%	271 95.4%	133 93.7%
Abnormal NCS	10 3.5%	13 4.6%	9 6.3%
Abnormal CS	0 0%	0 0%	0 0%
Normal	266 93.3%	260 91.5%	123 86.6%
Abnormal NCS	9 3.2%	9 3.2%	10 7%
Abnormal CS	0 0%	0 0%	0 0%
Normal	203 71.2%	212 74.6%	109 76.8%
Abnormal NCS	67 23.5%	54 19%	22 15.5%
Abnormal CS	15 5.3%	18 6.3%	11 7.7%
Normal	208 73%	204 71.8%	105 73.9%
Abnormal NCS	59 20.7%	55 19.4%	20 14.1%
Abnormal CS	8 2.8%	10 3.5%	8 5.6%
Normal	275 96.5%	269 94.7%	138 97.2%
Abnormal NCS	9 3.2%	13 4.6%	3 2.1%
Abnormal CS	1 0.4%	2 0.7%	1 0.7%
Normal	267 93.7%	258 90.8%	129 90.8%
Abnormal NCS	8 2.8%	10 3.5%	3 2.1%
Abnormal CS	0 0%	0 0%	0 0%
Normal	285 100%	283 99.6%	142 100%
Abnormal NCS	0 0%	1 0.4%	0 0%
Abnormal CS	0 0%	0 0%	0 0%
Normal	275 96.5%	268 94.4%	133 93.7%
Abnormal NCS	0 0%	1 0.4%	0 0%
Abnormal CS	0 0%	0 0%	0 0%
Normal	268 94%	264 93%	131 92.3%
Abnormal NCS	14 4.9%	17 6%	10 7%
Abnormal CS	3 1.1%	3 1.1%	1 0.7%
Normal	262 91.9%	257 90.5%	124 87.3%
Abnormal NCS	11 3.9%	10 3.5%	7 4.9%
Abnormal CS	2 0.7%	1 0.4%	1 0.7%
Normal	282 98.9%	278 97.9%	140 98.6%
Abnormal NCS	3 1.1%	5 1.8%	0 0%
Abnormal CS	0 0%	1 0.4%	2 1.4%
Normal	273 95.8%	262 92.3%	131 92.3%
Abnormal NCS	2 0.7%	6 2.1%	0 0%
Abnormal CS	0 0%	1 0.4%	2 1.4%
Normal	243 85.3%	243 85.6%	122 85.9%
Abnormal NCS	40 14%	36 12.7%	17 12%
Abnormal CS	2 0.7%	5 1.8%	3 2.1%
Normal	243 85.3%	235 82.7%	114 80.3%
Abnormal NCS	30 10.5%	30 10.6%	17 12%
Abnormal CS	2 0.7%	4 1.4%	2 1.4%
Normal	276 96.8%	277 97.5%	132 93%
Abnormal NCS	5 1.8%	5 1.8%	8 5.6%
Abnormal CS	4 1.4%	2 0.7%	2 1.4%
Normal	267 93.7%	262 92.3%	127 89.4%
Abnormal NCS	5 1.8%	6 2.1%	4 2.8%
Abnormal CS	3 1.1%	1 0.4%	2 1.4%

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) and week 52 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

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 14 mg	Liraglutide 1.8 mg	Placebo
Arm/Group Description	Participants were to take once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose-escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 52). In addition, participants were to take liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take once-daily liraglutide subcutaneous injection (under the skin) for 52 weeks. Participants started liraglutide at 0.6 mg and were dose-escalated in one-week increments until the final maintenance dose of 1.8 mg once-daily was reached (i.e. 0.6 mg from week 0 to week 1, 1.2 mg from week 1 to week 2 and 1.8 mg from week 2 to week 52). In addition, participants were to take oral semaglutide placebo tablets once-daily from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take both oral semaglutide placebo tablets and liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.
Measure Participants	285	284	142
Left eye - Normal to Normal	130 45.6%	144 50.7%	57 40.1%
Left eye - Normal to Abnormal NCS	10 3.5%	15 5.3%	5 3.5%
Left eye - Normal to Abnormal CS	4 1.4%	4 1.4%	2 1.4%
Left eye - Abnormal NCS to normal	15 5.3%	13 4.6%	5 3.5%
Left eye - Abnormal NCS to abnormal NCS	63 22.1%	43 15.1%	38 26.8%
Left eye - Abnormal NCS to abnormal CS	1 0.4%	1 0.4%	1 0.7%
Left eye - Abnormal CS to normal	1 0.4%	3 1.1%	0 0%
Left eye - Abnormal CS to abnormal NCS	5 1.8%	3 1.1%	2 1.4%
Left eye - Abnormal CS to abnormal CS	7 2.5%	12 4.2%	8 5.6%
Right eye - Normal to Normal	127 44.6%	150 52.8%	57 40.1%
Right eye - Normal to Abnormal NCS	10 3.5%	13 4.6%	7 4.9%
Right eye - Normal to Abnormal CS	3 1.1%	4 1.4%	2 1.4%
Right eye - Abnormal NCS to Normal	16 5.6%	12 4.2%	6 4.2%
Right eye - Abnormal NCS to Abnormal NCS	64 22.5%	42 14.8%	37 26.1%
Right eye - Abnormal NCS to Abnormal CS	2 0.7%	1 0.4%	1 0.7%
Right eye - Abnormal CS to Normal	2 0.7%	3 1.1%	1 0.7%
Right eye - Abnormal CS to Abnormal NCS	5 1.8%	2 0.7%	1 0.7%
Right eye - Abnormal CS to Abnormal CS	7 2.5%	11 3.9%	6 4.2%

33. Secondary Outcome

Title	Occurrence of Anti-semaglutide Binding Antibodies (Yes/no)
Description	This outcome measure is only applicable for the oral semaglutide 14 mg treatment arm. Number of participants who measured with anti-semaglutide binding antibodies anytime during post-baseline visits (weeks 0-57) 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 0-57

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Oral Semaglutide 14 mg
Arm/Group Description	Participants were to take once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose-escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 52). In addition, participants were to take liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.
Measure Participants	251
Count of Participants [Participants]	0 0%

34. Secondary Outcome

Title	Occurrence of Anti-semaglutide Neutralising Antibodies (Yes/no)
Description	This outcome measure is only applicable for the oral semaglutide 14 mg treatment arm. Number of participants who measured with anti-semaglutide neutralising antibodies anytime during post-baseline visits (weeks 0-57) 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 0-57

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Oral Semaglutide 14 mg
Arm/Group Description	Participants were to take once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose-escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 52). In addition, participants were to take liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.
Measure Participants	251
Count of Participants [Participants]	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 14 mg treatment arm. 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 0-57) 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 0-57

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Oral Semaglutide 14 mg
Arm/Group Description	Participants were to take once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose-escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 52). In addition, participants were to take liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.
Measure Participants	251
Count of Participants [Participants]	0 0%

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 14 mg treatment arm. Number of participants who measured with anti-semaglutide neutralising antibodies cross reacting with native GLP-1 anytime during post-baseline visits (weeks 0-57) 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 0-57

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Oral Semaglutide 14 mg
Arm/Group Description	Participants were to take once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose-escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 52). In addition, participants were to take liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.
Measure Participants	251
Count of Participants [Participants]	0 0%

37. Secondary Outcome

Title	Anti-semaglutide Binding Antibody Levels
Description	This outcome measure is only applicable for the oral semaglutide 14 mg treatment arm. It is based on the data from participants who were measured with anti-semaglutide antibodies anytime during post-baseline visits (weeks 0-57). 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 0-57

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 14 mg
Arm/Group Description	Participants were to take once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose-escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 52). In addition, participants were to take liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.
Measure Participants	0

38. Secondary Outcome

Title	Number of Treatment-emergent Severe or Blood Glucose-confirmed Symptomatic Hypoglycaemic Episodes
Description	Treatment emergent severe or BG confirmed symptomatic hypoglycaemic episodes were recorded during weeks 0-57 (52-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 0-57

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 14 mg	Liraglutide 1.8 mg	Placebo
Arm/Group Description	Participants were to take once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose-escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 52). In addition, participants were to take liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take once-daily liraglutide subcutaneous injection (under the skin) for 52 weeks. Participants started liraglutide at 0.6 mg and were dose-escalated in one-week increments until the final maintenance dose of 1.8 mg once-daily was reached (i.e. 0.6 mg from week 0 to week 1, 1.2 mg from week 1 to week 2 and 1.8 mg from week 2 to week 52). In addition, participants were to take oral semaglutide placebo tablets once-daily from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take both oral semaglutide placebo tablets and liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.
Measure Participants	285	284	142
Number [Episodes]	2	9	3

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 57 (52-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 0-57

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 14 mg	Liraglutide 1.8 mg	Placebo
Arm/Group Description	Participants were to take once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose-escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 52). In addition, participants were to take liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take once-daily liraglutide subcutaneous injection (under the skin) for 52 weeks. Participants started liraglutide at 0.6 mg and were dose-escalated in one-week increments until the final maintenance dose of 1.8 mg once-daily was reached (i.e. 0.6 mg from week 0 to week 1, 1.2 mg from week 1 to week 2 and 1.8 mg from week 2 to week 52). In addition, participants were to take oral semaglutide placebo tablets once-daily from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take both oral semaglutide placebo tablets and liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.
Measure Participants	285	284	142
Count of Participants [Participants]	2 0.7%	7 2.5%	3 2.1%

40. Secondary Outcome

Title	Change in DTSQs: Individual Items and Total Treatment Satisfaction Score (6 of the 8 Items Summed)
Description	Change from baseline (week 0) in Diabetes Treatment Satisfaction Questionnaire - status version (DTSQs) was evaluated at week 26 (wk 26) and week 52 (wk 52). The DTSQs items are scored on a 7-point graded response scale ranging from 6 to 0. Higher scores indicate higher levels of treatment satisfaction for DTSQs items 1, 4 -8. For items 2 and 3 a higher score indicates a higher patient perceived experience of hyperglycaemia and hypoglycaemia, respectively. Thus, lower scores indicate a perception of blood glucose levels being "none of the time" unacceptably high (item 2) or low (item 3). The domain score of total treatment satisfaction (total treatment satisfaction score) was computed by adding the six items scores 1, 4-8. The score has a minimum of 0 and a maximum of 36. A higher treatment satisfaction score indicates a higher level of treatment satisfaction.
Time Frame	Week 0, week 26, week 52

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 14 mg	Liraglutide 1.8 mg	Placebo
Arm/Group Description	Participants were to take once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose-escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 52). In addition, participants were to take liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take once-daily liraglutide subcutaneous injection (under the skin) for 52 weeks. Participants started liraglutide at 0.6 mg and were dose-escalated in one-week increments until the final maintenance dose of 1.8 mg once-daily was reached (i.e. 0.6 mg from week 0 to week 1, 1.2 mg from week 1 to week 2 and 1.8 mg from week 2 to week 52). In addition, participants were to take oral semaglutide placebo tablets once-daily from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.	Participants were to take both oral semaglutide placebo tablets and liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.
Measure Participants	285	284	142
Satisfaction with treatment: wk 26	0.72 (1.49)	0.73 (1.54)	0.28 (1.69)
Satisfaction with treatment: wk 52	0.67 (1.67)	0.70 (1.46)	0.48 (1.45)
Feeling of unacceptably high blood sugars: wk 26	-1.94 (2.03)	-1.72 (2.10)	-0.87 (2.11)
Feeling of unacceptably high blood sugars: wk 52	-1.97 (2.13)	-1.71 (2.11)	-1.04 (2.10)
Feeling of unacceptably low blood sugars: wk 26	-0.18 (1.81)	0.03 (1.90)	-0.07 (1.57)
Feeling of unacceptably low blood sugars: wk 52	-0.17 (1.85)	-0.06 (1.75)	-0.14 (1.45)
Convenience of treatment: wk 26	0.55 (1.38)	0.39 (1.48)	0.17 (1.81)
Convenience of treatment: wk 52	0.50 (1.47)	0.42 (1.44)	0.21 (1.75)
Flexibility of treatment: wk 26	0.45 (1.53)	0.43 (1.48)	0.09 (1.34)
Flexibility of treatment: wk 52	0.38 (1.52)	0.40 (1.62)	0.14 (1.51)
Satisfaction with understanding of diabetes: wk 26	0.66 (1.31)	0.52 (1.37)	0.38 (1.18)
Satisfaction with understanding of diabetes: wk 52	0.65 (1.29)	0.54 (1.41)	0.27 (1.38)
Recommending treatment to others: wk 26	0.57 (1.47)	0.63 (1.59)	0.10 (1.34)
Recommending treatment to others: wk 52	0.60 (1.55)	0.48 (1.61)	0.02 (1.70)
Satisfaction to continue present treatment: wk 26	0.64 (1.68)	0.74 (1.76)	0.22 (1.80)
Satisfaction to continue present treatment: wk 52	0.60 (1.81)	0.56 (1.74)	0.11 (1.77)
Total treatment satisfaction: wk 26	3.59 (6.12)	3.44 (6.51)	1.24 (6.71)
Total treatment satisfaction: wk 52	3.41 (6.81)	3.11 (6.93)	1.23 (6.96)

Adverse Events

Time Frame	Week 0 to week 57 (52 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 14 mg		Liraglutide 1.8 mg		Placebo
Arm/Group Description	Participants were to take once-daily oral semaglutide tablets for 52 weeks. Participants started oral semaglutide at 3 mg and were dose-escalated in 4-week increments until the final maintenance dose of 14 mg once-daily was reached (i.e. 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 52). In addition, participants were to take liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.		Participants were to take once-daily liraglutide subcutaneous injection (under the skin) for 52 weeks. Participants started liraglutide at 0.6 mg and were dose-escalated in one-week increments until the final maintenance dose of 1.8 mg once-daily was reached (i.e. 0.6 mg from week 0 to week 1, 1.2 mg from week 1 to week 2 and 1.8 mg from week 2 to week 52). In addition, participants were to take oral semaglutide placebo tablets once-daily from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.		Participants were to take both oral semaglutide placebo tablets and liraglutide placebo once-daily as a subcutaneous injection (under the skin) from week 0 to week 52. Participants were to continue their anti-diabetic background medication (metformin alone or in combination with a sodium-glucose co-transporter-2 [SGLT-2] inhibitor) throughout the entire trial.
All Cause Mortality
	Oral Semaglutide 14 mg		Liraglutide 1.8 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/285 (1.1%)		4/284 (1.4%)		1/142 (0.7%)
Serious Adverse Events
	Oral Semaglutide 14 mg		Liraglutide 1.8 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	31/285 (10.9%)		22/284 (7.7%)		15/142 (10.6%)
Cardiac disorders
Acute myocardial infarction	1/285 (0.4%)	1	0/284 (0%)	0	1/142 (0.7%)	1
Atrial fibrillation	1/285 (0.4%)	1	1/284 (0.4%)	1	0/142 (0%)	0
Atrial flutter	0/285 (0%)	0	0/284 (0%)	0	1/142 (0.7%)	1
Atrioventricular block second degree	1/285 (0.4%)	1	0/284 (0%)	0	0/142 (0%)	0
Cardiac failure chronic	0/285 (0%)	0	1/284 (0.4%)	1	0/142 (0%)	0
Coronary artery disease	1/285 (0.4%)	1	0/284 (0%)	0	0/142 (0%)	0
Coronary artery occlusion	0/285 (0%)	0	1/284 (0.4%)	1	0/142 (0%)	0
Myocardial infarction	2/285 (0.7%)	2	1/284 (0.4%)	1	0/142 (0%)	0
Ventricular extrasystoles	1/285 (0.4%)	1	0/284 (0%)	0	0/142 (0%)	0
Congenital, familial and genetic disorders
Respiratory tract malformation	1/285 (0.4%)	1	0/284 (0%)	0	0/142 (0%)	0
Ear and labyrinth disorders
Vertigo positional	0/285 (0%)	0	0/284 (0%)	0	1/142 (0.7%)	1
Endocrine disorders
Thyroid mass	0/285 (0%)	0	1/284 (0.4%)	1	0/142 (0%)	0
Eye disorders
Ophthalmic vein thrombosis	0/285 (0%)	0	1/284 (0.4%)	1	0/142 (0%)	0
Gastrointestinal disorders
Duodenal ulcer	0/285 (0%)	0	0/284 (0%)	0	1/142 (0.7%)	1
Gastritis	1/285 (0.4%)	1	0/284 (0%)	0	0/142 (0%)	0
Gastrooesophageal reflux disease	0/285 (0%)	0	0/284 (0%)	0	1/142 (0.7%)	1
Hiatus hernia	1/285 (0.4%)	1	0/284 (0%)	0	0/142 (0%)	0
Large intestine polyp	1/285 (0.4%)	1	0/284 (0%)	0	0/142 (0%)	0
Nausea	1/285 (0.4%)	1	0/284 (0%)	0	0/142 (0%)	0
Vomiting	1/285 (0.4%)	1	0/284 (0%)	0	0/142 (0%)	0
General disorders
Death	0/285 (0%)	0	1/284 (0.4%)	1	0/142 (0%)	0
Non-cardiac chest pain	1/285 (0.4%)	1	0/284 (0%)	0	0/142 (0%)	0
Hepatobiliary disorders
Cholecystitis	0/285 (0%)	0	1/284 (0.4%)	1	0/142 (0%)	0
Cholelithiasis	0/285 (0%)	0	1/284 (0.4%)	1	0/142 (0%)	0
Drug-induced liver injury	1/285 (0.4%)	1	0/284 (0%)	0	0/142 (0%)	0
Hepatic haematoma	0/285 (0%)	0	1/284 (0.4%)	1	0/142 (0%)	0
Infections and infestations
Cellulitis	1/285 (0.4%)	1	0/284 (0%)	0	0/142 (0%)	0
Chronic sinusitis	0/285 (0%)	0	0/284 (0%)	0	1/142 (0.7%)	1
Erysipelas	1/285 (0.4%)	1	0/284 (0%)	0	0/142 (0%)	0
Herpes zoster	1/285 (0.4%)	1	0/284 (0%)	0	0/142 (0%)	0
Otitis media	1/285 (0.4%)	1	0/284 (0%)	0	0/142 (0%)	0
Postoperative wound infection	1/285 (0.4%)	1	0/284 (0%)	0	0/142 (0%)	0
Sepsis	1/285 (0.4%)	2	0/284 (0%)	0	0/142 (0%)	0
Urinary tract infection	1/285 (0.4%)	1	0/284 (0%)	0	0/142 (0%)	0
Injury, poisoning and procedural complications
Accidental overdose	0/285 (0%)	0	0/284 (0%)	0	1/142 (0.7%)	1
Ankle fracture	0/285 (0%)	0	1/284 (0.4%)	1	0/142 (0%)	0
Meniscus injury	1/285 (0.4%)	1	1/284 (0.4%)	1	0/142 (0%)	0
Muscle rupture	1/285 (0.4%)	1	0/284 (0%)	0	0/142 (0%)	0
Spinal compression fracture	1/285 (0.4%)	1	0/284 (0%)	0	0/142 (0%)	0
Subdural haematoma	0/285 (0%)	0	1/284 (0.4%)	1	0/142 (0%)	0
Tibia fracture	0/285 (0%)	0	1/284 (0.4%)	1	0/142 (0%)	0
Investigations
Hepatic enzyme increased	0/285 (0%)	0	1/284 (0.4%)	1	0/142 (0%)	0
Investigation	1/285 (0.4%)	1	0/284 (0%)	0	0/142 (0%)	0
Lipase increased	1/285 (0.4%)	1	0/284 (0%)	0	0/142 (0%)	0
Weight decreased	1/285 (0.4%)	1	0/284 (0%)	0	0/142 (0%)	0
Metabolism and nutrition disorders
Cachexia	1/285 (0.4%)	1	0/284 (0%)	0	0/142 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	0/285 (0%)	0	0/284 (0%)	0	1/142 (0.7%)	1
Back pain	0/285 (0%)	0	1/284 (0.4%)	1	0/142 (0%)	0
Bursitis	1/285 (0.4%)	1	0/284 (0%)	0	0/142 (0%)	0
Intervertebral disc protrusion	1/285 (0.4%)	1	0/284 (0%)	0	0/142 (0%)	0
Ligamentitis	1/285 (0.4%)	1	0/284 (0%)	0	0/142 (0%)	0
Osteoarthritis	0/285 (0%)	0	2/284 (0.7%)	2	0/142 (0%)	0
Spinal osteoarthritis	1/285 (0.4%)	1	0/284 (0%)	0	0/142 (0%)	0
Tendon disorder	1/285 (0.4%)	1	0/284 (0%)	0	0/142 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign neoplasm of thyroid gland	1/285 (0.4%)	1	0/284 (0%)	0	0/142 (0%)	0
Colon adenoma	0/285 (0%)	0	1/284 (0.4%)	1	0/142 (0%)	0
Invasive ductal breast carcinoma	1/285 (0.4%)	1	0/284 (0%)	0	0/142 (0%)	0
Lung adenocarcinoma	1/285 (0.4%)	1	0/284 (0%)	0	0/142 (0%)	0
Oral fibroma	1/285 (0.4%)	1	0/284 (0%)	0	0/142 (0%)	0
Ovarian cancer metastatic	0/285 (0%)	0	1/284 (0.4%)	1	0/142 (0%)	0
Pancreatic carcinoma	0/285 (0%)	0	1/284 (0.4%)	1	0/142 (0%)	0
Papillary thyroid cancer	1/285 (0.4%)	1	0/284 (0%)	0	0/142 (0%)	0
Parathyroid tumour benign	0/285 (0%)	0	1/284 (0.4%)	1	0/142 (0%)	0
Thyroid cancer metastatic	0/285 (0%)	0	1/284 (0.4%)	1	0/142 (0%)	0
Nervous system disorders
Aphasia	0/285 (0%)	0	0/284 (0%)	0	1/142 (0.7%)	1
Carpal tunnel syndrome	1/285 (0.4%)	1	0/284 (0%)	0	0/142 (0%)	0
Cerebellar syndrome	0/285 (0%)	0	0/284 (0%)	0	1/142 (0.7%)	1
Cerebral infarction	1/285 (0.4%)	1	0/284 (0%)	0	0/142 (0%)	0
Cerebrovascular disorder	0/285 (0%)	0	0/284 (0%)	0	1/142 (0.7%)	1
Diabetic neuropathy	1/285 (0.4%)	1	0/284 (0%)	0	0/142 (0%)	0
Dizziness	1/285 (0.4%)	1	0/284 (0%)	0	0/142 (0%)	0
Facial paresis	0/285 (0%)	0	0/284 (0%)	0	1/142 (0.7%)	1
Headache	0/285 (0%)	0	0/284 (0%)	0	1/142 (0.7%)	1
Hemiparesis	0/285 (0%)	0	0/284 (0%)	0	1/142 (0.7%)	1
Ischaemic stroke	0/285 (0%)	0	0/284 (0%)	0	1/142 (0.7%)	1
Sciatica	0/285 (0%)	0	0/284 (0%)	0	1/142 (0.7%)	1
Syncope	1/285 (0.4%)	1	0/284 (0%)	0	0/142 (0%)	0
Trigeminal neuralgia	0/285 (0%)	0	1/284 (0.4%)	1	0/142 (0%)	0
Renal and urinary disorders
Nephrolithiasis	1/285 (0.4%)	1	0/284 (0%)	0	0/142 (0%)	0
Renal failure	0/285 (0%)	0	1/284 (0.4%)	1	0/142 (0%)	0
Ureterolithiasis	1/285 (0.4%)	1	0/284 (0%)	0	0/142 (0%)	0
Reproductive system and breast disorders
Menometrorrhagia	0/285 (0%)	0	0/284 (0%)	0	1/142 (0.7%)	1
Respiratory, thoracic and mediastinal disorders
Epistaxis	1/285 (0.4%)	1	0/284 (0%)	0	1/142 (0.7%)	1
Surgical and medical procedures
Hospitalisation	1/285 (0.4%)	1	0/284 (0%)	0	0/142 (0%)	0
Thyroidectomy	0/285 (0%)	0	1/284 (0.4%)	1	0/142 (0%)	0
Vascular disorders
Diabetic vascular disorder	0/285 (0%)	0	1/284 (0.4%)	1	0/142 (0%)	0
Hypertension	0/285 (0%)	0	0/284 (0%)	0	1/142 (0.7%)	1
Orthostatic hypotension	0/285 (0%)	0	1/284 (0.4%)	1	0/142 (0%)	0
Varicose vein	0/285 (0%)	0	0/284 (0%)	0	1/142 (0.7%)	1
Other (Not Including Serious) Adverse Events
	Oral Semaglutide 14 mg		Liraglutide 1.8 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	148/285 (51.9%)		120/284 (42.3%)		47/142 (33.1%)
Gastrointestinal disorders
Abdominal pain	16/285 (5.6%)	16	6/284 (2.1%)	6	3/142 (2.1%)	3
Constipation	22/285 (7.7%)	23	11/284 (3.9%)	12	4/142 (2.8%)	4
Diarrhoea	43/285 (15.1%)	59	31/284 (10.9%)	42	11/142 (7.7%)	11
Dyspepsia	16/285 (5.6%)	26	12/284 (4.2%)	13	0/142 (0%)	0
Nausea	55/285 (19.3%)	69	51/284 (18%)	67	5/142 (3.5%)	5
Vomiting	24/285 (8.4%)	28	13/284 (4.6%)	24	3/142 (2.1%)	3
Infections and infestations
Nasopharyngitis	41/285 (14.4%)	60	37/284 (13%)	59	15/142 (10.6%)	18
Investigations
Blood glucose increased	0/285 (0%)	0	2/284 (0.7%)	2	9/142 (6.3%)	10
Metabolism and nutrition disorders
Decreased appetite	16/285 (5.6%)	17	20/284 (7%)	23	0/142 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	11/285 (3.9%)	13	17/284 (6%)	19	5/142 (3.5%)	6
Nervous system disorders
Headache	27/285 (9.5%)	33	17/284 (6%)	24	8/142 (5.6%)	12

Limitations/Caveats

[Not Specified]

More Information

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.