PIONEER 5: Efficacy and Safety of Oral Semaglutide Versus Placebo in Subjects With Type 2 Diabetes and Moderate Renal Impairment

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02827708
• Collaborator: (none)
• Enrollment: 324
• Locations: 117
• Arms: 2
• Actual Duration (Months): 19.8
• Patients Per Site: 2.8
• Patients Per Site Per Month: 0.1

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 placebo in subjects with type 2 diabetes and moderate renal impairment.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 324 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Efficacy and Safety of Oral Semaglutide Versus Placebo in Subjects With Type 2 Diabetes and Moderate Renal Impairment
• Actual Study Start Date: Sep 20, 2016
• Actual Primary Completion Date: Apr 10, 2018
• Actual Study Completion Date: May 15, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Semaglutide	Drug: semaglutide; Oral administration once daily.
Placebo Comparator: Placebo	Drug: placebo; Oral administration once daily.

Outcome Measures

Primary Outcome Measures

1. Change in HbA1c [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 (kg) [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 FPG [Week 0, week 26]

   Change from baseline (week 0) in fasting plasma glucose (FPG) was evaluated at week 26. 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 0, week 26]

   Relative change from baseline (week 0) in body weight (kg) was evaluated at week 26. 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 BMI [Week 0, week 26]

   Change from baseline (week 0) in body mass index (BMI) was evaluated at week 26. 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 Waist Circumference [Week 0, week 26]

   Change from baseline (week 0) in waist circumference was evaluated at week 26. 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. Participants Who Achieve HbA1c <7.0% (53 mmol/Mol), ADA Target (Yes/no) [Week 26]

   Participants who achieved HbA1c <7.0% (American Diabetes Association (ADA) target) (yes/no), was evaluated at week 26. 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. Participants Who Achieve HbA1c ≤6.5% (48 mmol/Mol), AACE Target (Yes/no) [Week 26]

   Participants who achieved HbA1c ≤6.5% (American Association of Clinical Endocrinologists (AACE) target) (yes/no), was evaluated at week 26. 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. Participants Who Achieve Weight Loss ≥5% (Yes/no) [Week 26]

   Participants who achieved weight loss ≥5% of their baseline body weight (yes/no) was evaluated at week 26. 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. Participants Who Achieve Weight Loss ≥10% (Yes/no) [Week 26]

   Participants who achieved weight loss of ≥10% of their baseline body weight (yes/no) was evaluated at week 26. 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. 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]

    Participants who achieved HbA1c <7.0 % without severe or blood glucose (BG) confirmed symptomatic hypoglycaemia and without weight gain (yes/no) was evaluated at week 26. 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.

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

    Participants who achieved HbA1c reduction ≥1% and weight loss of ≥3% (yes/no) was evaluated at week 26. 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 Total Cholesterol (Ratio to Baseline) [Week 0, week 26]

    Change from baseline (week 0) in total cholesterol (mmol/L) at week 26 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 LDL Cholesterol (Ratio to Baseline) [Week 0, week 26]

    Change from baseline (week 0) in low-density lipoprotein (LDL) cholesterol (mmol/L) at week 26 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 HDL Cholesterol (Ratio to Baseline) [Week 0, week 26]

    Change from baseline (week 0) in high-density lipoprotein (HDL) cholesterol (mmol/L) at week 26 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.

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

    Change from baseline (week 0) in triglycerides (mmol/L) at week 26 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.

16. Change in CRP (Ratio to Baseline) [Week 0, week 26]

    Change from baseline (week 0) in C-reactive protein (CRP) (mg/L) at week 26 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.

17. Time to Additional Anti-diabetic Medication [Weeks 0-26]

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

18. Time to Rescue Medication [Weeks 0-26]

    Presented results are the number of participants who had taken rescue medication anytime during the period, from week 0 to week 26. 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.

19. Number of TEAEs [Weeks 0-31]

    Treatment emergent adverse events (TEAEs) were recorded from week 0 to week 31 (26 weeks treatment period + 5 weeks follow-up period). Adverse events (AEs) with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.

20. Number of Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes [Weeks 0-31]

    Treatment emergent severe or BG-confirmed symptomatic hypoglycaemic episodes were recorded from week 0 to week 31 (26 weeks treatment period + 5 weeks follow-up period). Hypoglycaemic episodes with onset during the first dose of trial product until last dose of trial product were considered treatment -emergent. Severe or BG-confirmed symptomatic hypoglycaemia was defined as an episode, that is severe according to the ADA classification or BG-confirmed by a plasma glucose value <3.1 mmol/L with symptoms consistent with hypoglycaemia. 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.

21. Participants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes (Yes/no) [Weeks 0-31]

    Number of participants with treatment emergent severe or BG-confirmed symptomatic hypoglycaemic episodes was recorded from week 0 to week 31 (26 weeks treatment period + 5 weeks follow-up period). Hypoglycaemic episodes with onset during the first dose of trial product until last dose of trial product were considered treatment -emergent. Severe or BG-confirmed symptomatic hypoglycaemia was defined as an episode, that is severe according to the ADA classification or BG-confirmed by a plasma glucose value <3.1 mmol/L with symptoms consistent with hypoglycaemia. 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.

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

    Change from baseline (week 0) in amylase (units/litre (U/L)) at week 26 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.

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

    Change from baseline (week 0) in lipase (U/L) at week 26 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.

24. Change in Pulse Rate [Week 0, week 26]

    Change from baseline (week 0) in pulse rate was evaluated at week 26. 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.

25. Change in Blood Pressure (Systolic and Diastolic Blood Pressure) [Week 0, week 26]

    Change from baseline (week 0) in systolic and diastolic blood pressure was evaluated at week 26. 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 Urinary Albumin to Creatinine Ratio (Ratio to Baseline) [Week 0, week 26]

    Change from baseline (week 0) in urinary albumin to creatinine ratio (mg/mmol) at week 26 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 ECG [Week 0, week 26]

    Change from baseline (week 0) in electrocardiogram (ECG) was evaluated at week 26. 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. 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.

28. Change in Physical Examination [Week -2, week 26]

    Participants with physical examination findings, normal, abnormal NCS and abnormal CS at baseline (week [wk] -2) and wk 26 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) Nervous system (central and peripheral); 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.

29. Change in Eye Examination [Week -2, week 26]

    Participants with eye examination findings, normal, abnormal NCS and abnormal CS at baseline (week -2) and week 26 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.

30. Occurrence of Anti-semaglutide Binding Antibodies (Yes/no) [Weeks 0-31]

    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 0-31) 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.

31. Occurrence of Anti-semaglutide Neutralising Antibodies (Yes/no) [Weeks 0-31]

    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 0-31) 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 Cross Reacting With Native GLP-1 (Yes/no) [Weeks 0-31]

    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 0-31) 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 Cross Reacting With Native GLP-1 (Yes/no) [Weeks 0-31]

    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 0-31) 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. Anti-semaglutide Binding Antibody Levels [Weeks 0-31]

    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 0-31). 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.

35. Semaglutide Plasma Concentrations for Population PK Analyses [Weeks 0-26]

    This outcome measure is only applicable for the oral semaglutide 14 mg treatment arm. Semaglutide plasma concentrations were measured at weeks 4, 8, 14 and 26. 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.

36. SNAC Plasma Concentrations [Weeks 0-26]

    This outcome measure is only applicable for the oral semaglutide 14 mg treatment arm. Sodium N-[8-(2-hydroxybenzoyl) amino]caprylate (SNAC) plasma concentrations were measured after 25 and 40 minutes post-dose at weeks 4, 14 and 26. 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.

37. Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS) [Week 0, week 26]

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

38. Change in DTSQs: Individual Items and Treatment Satisfaction Score (6 of the 8 Items Summed) [Week 0, week 26]

    Change from baseline (week 0) in Diabetes Treatment Satisfaction Questionnaire - status version (DTSQs) was evaluated at week 26. 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.

39. Change in Urinalysis [Week -2, week 26]

    Participants with urinalysis, "leukocytes and erythrocytes" findings, negative, trace, small, moderate or large at baseline (week [wk] 0) and wk 26 are presented. Participants with urinalysis, "nitrit" findings, negative or positive at baseline (wk 0) and wk 26 are presented. 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.

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

• 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 mmol/mol) (both inclusive)

• Moderate renal impairment defined as estimated glomerular filtration rate of 30-59 mL/min/1.73 m^2 as per Chronic Kidney Disease Epidemiology Collaboration formula

• Stable daily dose(s) within 90 days prior to the day of screening of any of the following treatment regimens:

• 1-2 of the following oral anti-diabetic drugs:

• Metformin equal or above 1500 mg or maximum tolerated dose documented in the subject medical record),

• Sulfonylurea (equal or above half of the maximum approved dose according to local label or maximum tolerated dose as documented in subject medical record)

• Basal insulin alone (20% change in total daily dose of insulin glargine, insulin detemir, insulin degludec or NPH insulin) or

• Metformin (equal or above 1500 mg or maximum tolerated dose documented in the subject medical record) in combination with basal insulin (20% change in total daily dose of insulin glargine, insulin detemir, insulin degludec or NPH insulin)

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 or Medullary Thyroid Carcinoma

• History of pancreatitis (acute or chronic)

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

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

• Subjects presently classified as being in New York Heart Association Class IV

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

• Subjects with alanine aminotransferase above 2.5 x upper normal limit

• Rapidly progressing renal disease (e.g. such as acute glomerulonephritis) as judged by the investigator or known nephrotic albuminuria (above 2200 mg/24 hours or above 2200 mg/g)

• Use of systemic immunosuppressive treatment within 90 days prior to screening

• 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

• Known hypoglycaemic unawareness and/or recurrent severe hypoglycaemic episodes as judged by the investigator

• 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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Tuscumbia	Alabama	United States	35674
2	Novo Nordisk Investigational Site	Bermuda Dunes	California	United States	92203
3	Novo Nordisk Investigational Site	Concord	California	United States	94520
4	Novo Nordisk Investigational Site	Costa Mesa	California	United States	92627
5	Novo Nordisk Investigational Site	Fresno	California	United States	93720
6	Novo Nordisk Investigational Site	La Jolla	California	United States	92161-0002
7	Novo Nordisk Investigational Site	San Ramon	California	United States	94583
8	Novo Nordisk Investigational Site	Danbury	Connecticut	United States	06810
9	Novo Nordisk Investigational Site	Norwalk	Connecticut	United States	06851
10	Novo Nordisk Investigational Site	Waterbury	Connecticut	United States	06708
11	Novo Nordisk Investigational Site	Clearwater	Florida	United States	33756
12	Novo Nordisk Investigational Site	Cooper City	Florida	United States	33024
13	Novo Nordisk Investigational Site	Jacksonville	Florida	United States	32258
14	Novo Nordisk Investigational Site	Miami Lakes	Florida	United States	33014
15	Novo Nordisk Investigational Site	New Port Richey	Florida	United States	34652
16	Novo Nordisk Investigational Site	Orlando	Florida	United States	32804
17	Novo Nordisk Investigational Site	Palm Harbor	Florida	United States	34684
18	Novo Nordisk Investigational Site	Pembroke Pines	Florida	United States	33027
19	Novo Nordisk Investigational Site	Atlanta	Georgia	United States	30339
20	Novo Nordisk Investigational Site	Atlanta	Georgia	United States	30342
21	Novo Nordisk Investigational Site	Lawrenceville	Georgia	United States	30046
22	Novo Nordisk Investigational Site	Marietta	Georgia	United States	30060
23	Novo Nordisk Investigational Site	Roswell	Georgia	United States	30076
24	Novo Nordisk Investigational Site	Gurnee	Illinois	United States	60031
25	Novo Nordisk Investigational Site	Avon	Indiana	United States	46123
26	Novo Nordisk Investigational Site	Franklin	Indiana	United States	46131
27	Novo Nordisk Investigational Site	Slidell	Louisiana	United States	70461-4231
28	Novo Nordisk Investigational Site	Baltimore	Maryland	United States	21204
29	Novo Nordisk Investigational Site	Baltimore	Maryland	United States	21287
30	Novo Nordisk Investigational Site	Buckley	Michigan	United States	49620
31	Novo Nordisk Investigational Site	Omaha	Nebraska	United States	68198
32	Novo Nordisk Investigational Site	Lebanon	New Hampshire	United States	03756
33	Novo Nordisk Investigational Site	Nashua	New Hampshire	United States	03063
34	Novo Nordisk Investigational Site	Teaneck	New Jersey	United States	07666
35	Novo Nordisk Investigational Site	Albany	New York	United States	12206
36	Novo Nordisk Investigational Site	New Hyde Park	New York	United States	11042
37	Novo Nordisk Investigational Site	Northport	New York	United States	11768
38	Novo Nordisk Investigational Site	West Seneca	New York	United States	14224
39	Novo Nordisk Investigational Site	Asheboro	North Carolina	United States	27203
40	Novo Nordisk Investigational Site	Whiteville	North Carolina	United States	28472
41	Novo Nordisk Investigational Site	Wilmington	North Carolina	United States	28401
42	Novo Nordisk Investigational Site	Fargo	North Dakota	United States	58103
43	Novo Nordisk Investigational Site	Dayton	Ohio	United States	45439
44	Novo Nordisk Investigational Site	Delaware	Ohio	United States	43015
45	Novo Nordisk Investigational Site	Franklin	Ohio	United States	45005
46	Novo Nordisk Investigational Site	Norman	Oklahoma	United States	73069
47	Novo Nordisk Investigational Site	Murrells Inlet	South Carolina	United States	29576
48	Novo Nordisk Investigational Site	Myrtle Beach	South Carolina	United States	29572
49	Novo Nordisk Investigational Site	Kingsport	Tennessee	United States	37660
50	Novo Nordisk Investigational Site	Amarillo	Texas	United States	79106
51	Novo Nordisk Investigational Site	Dallas	Texas	United States	75231
52	Novo Nordisk Investigational Site	Houston	Texas	United States	77058
53	Novo Nordisk Investigational Site	Houston	Texas	United States	77061
54	Novo Nordisk Investigational Site	Houston	Texas	United States	77081
55	Novo Nordisk Investigational Site	Midland	Texas	United States	79707
56	Novo Nordisk Investigational Site	San Antonio	Texas	United States	78212
57	Novo Nordisk Investigational Site	Richmond	Virginia	United States	23219
58	Novo Nordisk Investigational Site	Winchester	Virginia	United States	22601-3834
59	Novo Nordisk Investigational Site	Winchester	Virginia	United States	22601
60	Novo Nordisk Investigational Site	Olympia	Washington	United States	98502
61	Novo Nordisk Investigational Site	Aalborg		Denmark	9000
62	Novo Nordisk Investigational Site	Gentofte		Denmark	2820
63	Novo Nordisk Investigational Site	Hvidovre		Denmark	2650
64	Novo Nordisk Investigational Site	København S		Denmark	2300
65	Novo Nordisk Investigational Site	Køge		Denmark	4600
66	Novo Nordisk Investigational Site	Svendborg		Denmark	5700
67	Novo Nordisk Investigational Site	Århus C		Denmark	8000
68	Novo Nordisk Investigational Site	Espoo		Finland	02230
69	Novo Nordisk Investigational Site	Helsinki		Finland	00250
70	Novo Nordisk Investigational Site	Kerava		Finland	FI-04200
71	Novo Nordisk Investigational Site	Kuopio		Finland	70100
72	Novo Nordisk Investigational Site	Oulu		Finland	90100
73	Novo Nordisk Investigational Site	Turku		Finland	20520
74	Novo Nordisk Investigational Site	Ähtäri		Finland	63700
75	Novo Nordisk Investigational Site	Haifa		Israel	31096
76	Novo Nordisk Investigational Site	Haifa		Israel
77	Novo Nordisk Investigational Site	Jerusalem		Israel	91120
78	Novo Nordisk Investigational Site	Kfar Saba		Israel	44281
79	Novo Nordisk Investigational Site	Rehovot		Israel	76100
80	Novo Nordisk Investigational Site	Tel Hashomer		Israel	52621
81	Novo Nordisk Investigational Site	Tel-Aviv		Israel	62038
82	Novo Nordisk Investigational Site	Poznan		Poland	60-589
83	Novo Nordisk Investigational Site	Zabrze		Poland	41-800
84	Novo Nordisk Investigational Site	Barnaul		Russian Federation	656024
85	Novo Nordisk Investigational Site	Barnaul		Russian Federation	656045
86	Novo Nordisk Investigational Site	Belgorod		Russian Federation	308007
87	Novo Nordisk Investigational Site	Chelyabinsk		Russian Federation	454000
88	Novo Nordisk Investigational Site	Dzerzhinskiy		Russian Federation	140091
89	Novo Nordisk Investigational Site	Kazan		Russian Federation	420061
90	Novo Nordisk Investigational Site	Moscow		Russian Federation	117036
91	Novo Nordisk Investigational Site	Penza		Russian Federation	440026
92	Novo Nordisk Investigational Site	Saint-Petersburg		Russian Federation	190068
93	Novo Nordisk Investigational Site	Saint-Petersburg		Russian Federation	194358
94	Novo Nordisk Investigational Site	Saint-Petersburg		Russian Federation	199226
95	Novo Nordisk Investigational Site	Saratov		Russian Federation	410039
96	Novo Nordisk Investigational Site	Saratov		Russian Federation	410053
97	Novo Nordisk Investigational Site	Tomsk		Russian Federation	634050
98	Novo Nordisk Investigational Site	Ulianovsk		Russian Federation	432063
99	Novo Nordisk Investigational Site	Volgograd		Russian Federation	400138
100	Novo Nordisk Investigational Site	Voronezh		Russian Federation	394018
101	Novo Nordisk Investigational Site	Yaroslavl		Russian Federation	150062
102	Novo Nordisk Investigational Site	Yoshkar-Ola		Russian Federation	424004
103	Novo Nordisk Investigational Site	Göteborg		Sweden	42144
104	Novo Nordisk Investigational Site	Lund		Sweden	222 22
105	Novo Nordisk Investigational Site	Skövde		Sweden	54150
106	Novo Nordisk Investigational Site	Uppsala		Sweden	75185
107	Novo Nordisk Investigational Site	Vindeln		Sweden	922 31
108	Novo Nordisk Investigational Site	Örebro		Sweden	701 85
109	Novo Nordisk Investigational Site	Bexhill-on-Sea		United Kingdom	TN39 4SP
110	Novo Nordisk Investigational Site	Doncaster		United Kingdom	DN5 0AT
111	Novo Nordisk Investigational Site	Edinburgh		United Kingdom	EH4 2XU
112	Novo Nordisk Investigational Site	Glasgow		United Kingdom	G31 2ER
113	Novo Nordisk Investigational Site	Hull		United Kingdom	HU3 2RW
114	Novo Nordisk Investigational Site	Milton Keynes		United Kingdom	MK6 5LD
115	Novo Nordisk Investigational Site	Rothwell		United Kingdom	NN14 6JQ
116	Novo Nordisk Investigational Site	Sheffield		United Kingdom	S5 7AU
117	Novo Nordisk Investigational Site	Wellingborough		United Kingdom	NN8 4RW

Sponsors and Collaborators

• Novo Nordisk A/S

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Dec 13, 2018
• Statistical Analysis Plan - Dec 13, 2018

More Information

Additional Information:

• Clinical Trials at Novo Nordisk

Publications

None provided.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT02827708
• Other Study ID Numbers: NN9924-4234; 2015-005326-19; U1111-1176-9230
• First Posted: Jul 11, 2016
• Last Update Posted: Feb 17, 2020
• Last Verified: Feb 1, 2020

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

Study Results

Participant Flow

Recruitment Details	The trial was conducted in 8 countries (107 sites screened/88 randomised subjects), as follows: Denmark: 7/4; Finland: 7/7; Israel: 7/6; Poland: 2/2; Russian Federation: 19/18; Sweden: 6/4; United Kingdom: 9/7; United States (US):50/40. In addition, 10 sites in the US were approved by the institutional review board, but didn't randomise any subject
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	Placebo
Arm/Group Description	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Participants were to take oral semaglutide placebo tablets once daily from week 0 to week 26.
Period Title: Overall Study
STARTED	163	161
Full Analysis Set (FAS)	163	161
Safety Analysis Set (SAS)	163	161
COMPLETED	158	156
NOT COMPLETED	5	5

Baseline Characteristics

Arm/Group Title	Oral Semaglutide 14 mg	Placebo	Total
Arm/Group Description	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Participants were to take oral semaglutide placebo tablets once daily from week 0 to week 26.	Total of all reporting groups
Overall Participants	163	161	324
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	71 (8)	70 (8)	70 (8)
Sex: Female, Male (Count of Participants)
Female	80 49.1%	88 54.7%	168 51.9%
Male	83 50.9%	73 45.3%	156 48.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	7 4.3%	14 8.7%	21 6.5%
Not Hispanic or Latino	156 95.7%	147 91.3%	303 93.5%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	1 0.6%	0 0%	1 0.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	4 2.5%	9 5.6%	13 4%
White	158 96.9%	152 94.4%	310 95.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Glycosylated haemoglobin (HbA1c) (Percentage of HbA1c) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percentage of HbA1c]	8.0 (0.7)	7.9 (0.7)	8.0 (0.7)

Outcome Measures

1. Primary Outcome

Title	Change in HbA1c
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	Placebo
Arm/Group Description	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Participants were to take oral semaglutide placebo tablets once daily from week 0 to week 26.
Measure Participants	163	161
In-trial	-1.1 (1.0)	-0.2 (0.9)
On-treatment without rescue medication	-1.2 (0.9)	-0.1 (0.9)

Statistical Analysis 1

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 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	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.
	Method	Pattern Mixture model
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-0.8
	Confidence Interval	(2-Sided) 95%; -1.0 to -0.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 14 mg - Placebo

Statistical Analysis 2

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, interaction strata and region as categorical fixed effects and the baseline value as 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.
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-1.0
	Confidence Interval	() 95%; -1.2 to -0.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 14 mg - Placebo

2. Secondary Outcome

Title	Change in Body Weight (kg)
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	Placebo
Arm/Group Description	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Participants were to take oral semaglutide placebo tablets once daily from week 0 to week 26.
Measure Participants	163	161
In-trial	-3.5 (3.8)	-0.9 (2.9)
On-treatment without rescue medication	-3.9 (3.6)	-0.9 (2.9)

Statistical Analysis 1

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.
	Method	Pattern Mixture model
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-2.5
	Confidence Interval	(2-Sided) 95%; -3.2 to -1.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 14 mg - Placebo

Statistical Analysis 2

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, interaction strata and region as categorical fixed effects and the baseline value as 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.
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-2.7
	Confidence Interval	(2-Sided) 95%; -3.5 to -1.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Oral semaglutide 14 mg - Placebo

3. Secondary Outcome

Title	Change in FPG
Description	Change from baseline (week 0) in fasting plasma glucose (FPG) was evaluated at week 26. 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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Oral Semaglutide 14 mg	Placebo
Arm/Group Description	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Participants were to take oral semaglutide placebo tablets once daily from week 0 to week 26.
Measure Participants	151	151
Mean (Standard Deviation) [mmol/L]	-1.58 (2.96)	-0.34 (3.03)

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Oral Semaglutide 14 mg	Placebo
Arm/Group Description	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Participants were to take oral semaglutide placebo tablets once daily from week 0 to week 26.
Measure Participants	154	155
Mean (Standard Deviation) [Percentage change]	-3.75 (4.10)	-0.92 (3.13)

5. Secondary Outcome

Title	Change in BMI
Description	Change from baseline (week 0) in body mass index (BMI) was evaluated at week 26. 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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Oral Semaglutide 14 mg	Placebo
Arm/Group Description	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Participants were to take oral semaglutide placebo tablets once daily from week 0 to week 26.
Measure Participants	154	155
Mean (Standard Deviation) [kg/m^2]	-1.2 (1.3)	-0.3 (1.0)

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Oral Semaglutide 14 mg	Placebo
Arm/Group Description	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Participants were to take oral semaglutide placebo tablets once daily from week 0 to week 26.
Measure Participants	152	154
Mean (Standard Deviation) [Centimetre (cm)]	-2.8 (4.9)	-0.7 (3.8)

7. 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 week 26. 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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Oral Semaglutide 14 mg	Placebo
Arm/Group Description	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Participants were to take oral semaglutide placebo tablets once daily from week 0 to week 26.
Measure Participants	154	155
Yes	89 54.6%	35 21.7%
No	65 39.9%	120 74.5%

8. Secondary Outcome

Title	Participants Who Achieve HbA1c ≤6.5% (48 mmol/Mol), AACE Target (Yes/no)
Description	Participants who achieved HbA1c ≤6.5% (American Association of Clinical Endocrinologists (AACE) target) (yes/no), was evaluated at week 26. 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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Oral Semaglutide 14 mg	Placebo
Arm/Group Description	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Participants were to take oral semaglutide placebo tablets once daily from week 0 to week 26.
Measure Participants	154	155
Yes	60 36.8%	12 7.5%
No	94 57.7%	143 88.8%

9. Secondary Outcome

Title	Participants Who Achieve Weight Loss ≥5% (Yes/no)
Description	Participants who achieved weight loss ≥5% of their baseline body weight (yes/no) was evaluated at week 26. 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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Oral Semaglutide 14 mg	Placebo
Arm/Group Description	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Participants were to take oral semaglutide placebo tablets once daily from week 0 to week 26.
Measure Participants	154	155
Yes	55 33.7%	15 9.3%
No	99 60.7%	140 87%

10. Secondary Outcome

Title	Participants Who Achieve Weight Loss ≥10% (Yes/no)
Description	Participants who achieved weight loss of ≥10% of their baseline body weight (yes/no) was evaluated at week 26. 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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Oral Semaglutide 14 mg	Placebo
Arm/Group Description	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Participants were to take oral semaglutide placebo tablets once daily from week 0 to week 26.
Measure Participants	154	155
Yes	13 8%	0 0%
No	141 86.5%	155 96.3%

11. 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 <7.0 % without severe or blood glucose (BG) confirmed symptomatic hypoglycaemia and without weight gain (yes/no) was evaluated at week 26. 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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Oral Semaglutide 14 mg	Placebo
Arm/Group Description	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Participants were to take oral semaglutide placebo tablets once daily from week 0 to week 26.
Measure Participants	154	155
Yes	78 47.9%	27 16.8%
No	76 46.6%	128 79.5%

12. 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 ≥1% and weight loss of ≥3% (yes/no) was evaluated at week 26. 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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Oral Semaglutide 14 mg	Placebo
Arm/Group Description	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Participants were to take oral semaglutide placebo tablets once daily from week 0 to week 26.
Measure Participants	154	155
Yes	60 36.8%	12 7.5%
No	94 57.7%	143 88.8%

13. Secondary Outcome

Title	Change in Total Cholesterol (Ratio to Baseline)
Description	Change from baseline (week 0) in total cholesterol (mmol/L) at week 26 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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Oral Semaglutide 14 mg	Placebo
Arm/Group Description	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Participants were to take oral semaglutide placebo tablets once daily from week 0 to week 26.
Measure Participants	148	153
Geometric Mean (Geometric Coefficient of Variation) [Ratio of total cholesterol]	0.97 (20.1)	1.00 (23.0)

14. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Oral Semaglutide 14 mg	Placebo
Arm/Group Description	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Participants were to take oral semaglutide placebo tablets once daily from week 0 to week 26.
Measure Participants	148	152
Geometric Mean (Geometric Coefficient of Variation) [Ratio of LDL cholesterol]	0.97 (32.7)	1.00 (38.2)

15. Secondary Outcome

Title	Change in HDL Cholesterol (Ratio to Baseline)
Description	Change from baseline (week 0) in high-density lipoprotein (HDL) cholesterol (mmol/L) at week 26 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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Oral Semaglutide 14 mg	Placebo
Arm/Group Description	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Participants were to take oral semaglutide placebo tablets once daily from week 0 to week 26.
Measure Participants	148	153
Geometric Mean (Geometric Coefficient of Variation) [Ratio of HDL cholesterol]	1.02 (17.5)	1.02 (15.4)

16. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Oral Semaglutide 14 mg	Placebo
Arm/Group Description	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Participants were to take oral semaglutide placebo tablets once daily from week 0 to week 26.
Measure Participants	148	153
Geometric Mean (Geometric Coefficient of Variation) [Ratio of triglycerides]	0.87 (37.7)	0.95 (37.1)

17. Secondary Outcome

Title	Change in CRP (Ratio to Baseline)
Description	Change from baseline (week 0) in C-reactive protein (CRP) (mg/L) at week 26 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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Oral Semaglutide 14 mg	Placebo
Arm/Group Description	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Participants were to take oral semaglutide placebo tablets once daily from week 0 to week 26.
Measure Participants	152	154
Geometric Mean (Geometric Coefficient of Variation) [Ratio of CRP]	0.86 (135.1)	1.00 (136.0)

18. 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 period, from week 0 to week 26. 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 26), 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 0-26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Oral Semaglutide 14 mg	Placebo
Arm/Group Description	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Participants were to take oral semaglutide placebo tablets once daily from week 0 to week 26.
Measure Participants	163	161
Count of Participants [Participants]	12 7.4%	21 13%

Statistical Analysis 1

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, interaction 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	=0.1834
	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	0.64
	Confidence Interval	(2-Sided) 95%; 0.34 to 1.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

19. Secondary Outcome

Title	Time to Rescue Medication
Description	Presented results are the number of participants who had taken rescue medication anytime during the period, from week 0 to week 26. 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 0-26

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Oral Semaglutide 14 mg	Placebo
Arm/Group Description	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Participants were to take oral semaglutide placebo tablets once daily from week 0 to week 26.
Measure Participants	163	161
Count of Participants [Participants]	7 4.3%	16 9.9%

Statistical Analysis 1

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, interaction 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	=0.0610
	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	0.43
	Confidence Interval	(2-Sided) 95%; 0.17 to 1.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

20. Secondary Outcome

Title	Number of TEAEs
Description	Treatment emergent adverse events (TEAEs) were recorded from week 0 to week 31 (26 weeks treatment period + 5 weeks follow-up period). Adverse events (AEs) with onset during the on-treatment observation period were considered treatment-emergent. On-treatment observation period was defined as the time period when a participant was on treatment with trial product, including any period after initiation of rescue medication.
Time Frame	Weeks 0-31

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	Placebo
Arm/Group Description	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Participants were to take oral semaglutide placebo tablets once daily from week 0 to week 26.
Measure Participants	163	161
Number [Events]	463	331

21. Secondary Outcome

Title	Number of Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes
Description	Treatment emergent severe or BG-confirmed symptomatic hypoglycaemic episodes were recorded from week 0 to week 31 (26 weeks treatment period + 5 weeks follow-up period). Hypoglycaemic episodes with onset during the first dose of trial product until last dose of trial product were considered treatment -emergent. Severe or BG-confirmed symptomatic hypoglycaemia was defined as an episode, that is severe according to the ADA classification or BG-confirmed by a plasma glucose value <3.1 mmol/L with symptoms consistent with hypoglycaemia. 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	Weeks 0-31

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	Placebo
Arm/Group Description	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Participants were to take oral semaglutide placebo tablets once daily from week 0 to week 26.
Measure Participants	163	161
Number [Episodes]	17	3

22. Secondary Outcome

Title	Participants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes (Yes/no)
Description	Number of participants with treatment emergent severe or BG-confirmed symptomatic hypoglycaemic episodes was recorded from week 0 to week 31 (26 weeks treatment period + 5 weeks follow-up period). Hypoglycaemic episodes with onset during the first dose of trial product until last dose of trial product were considered treatment -emergent. Severe or BG-confirmed symptomatic hypoglycaemia was defined as an episode, that is severe according to the ADA classification or BG-confirmed by a plasma glucose value <3.1 mmol/L with symptoms consistent with hypoglycaemia. 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	Weeks 0-31

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	Placebo
Arm/Group Description	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Participants were to take oral semaglutide placebo tablets once daily from week 0 to week 26.
Measure Participants	163	161
Count of Participants [Participants]	9 5.5%	3 1.9%

23. Secondary Outcome

Title	Change in Amylase (Ratio to Baseline)
Description	Change from baseline (week 0) in amylase (units/litre (U/L)) at week 26 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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Oral Semaglutide 14 mg	Placebo
Arm/Group Description	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Participants were to take oral semaglutide placebo tablets once daily from week 0 to week 26.
Measure Participants	129	140
Geometric Mean (Geometric Coefficient of Variation) [Ratio of amylase]	1.09 (22.9)	0.99 (25.6)

24. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Oral Semaglutide 14 mg	Placebo
Arm/Group Description	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Participants were to take oral semaglutide placebo tablets once daily from week 0 to week 26.
Measure Participants	129	140
Geometric Mean (Geometric Coefficient of Variation) [Ratio of lipase]	1.16 (57.6)	0.94 (52.5)

25. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Oral Semaglutide 14 mg	Placebo
Arm/Group Description	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Participants were to take oral semaglutide placebo tablets once daily from week 0 to week 26.
Measure Participants	133	141
Mean (Standard Deviation) [Beats/minute]	1 (9)	-1 (9)

26. Secondary Outcome

Title	Change in Blood Pressure (Systolic and Diastolic Blood Pressure)
Description	Change from baseline (week 0) in systolic and diastolic blood pressure was evaluated at week 26. 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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Oral Semaglutide 14 mg	Placebo
Arm/Group Description	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Participants were to take oral semaglutide placebo tablets once daily from week 0 to week 26.
Measure Participants	133	141
Systolic blood pressure	-8 (14)	0 (13)
Diastolic blood pressure	-3 (9)	0 (8)

27. Secondary Outcome

Title	Change in Urinary Albumin to Creatinine Ratio (Ratio to Baseline)
Description	Change from baseline (week 0) in urinary albumin to creatinine ratio (mg/mmol) at week 26 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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Oral Semaglutide 14 mg	Placebo
Arm/Group Description	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Participants were to take oral semaglutide placebo tablets once daily from week 0 to week 26.
Measure Participants	131	136
Geometric Mean (Geometric Coefficient of Variation) [Ratio]	0.86 (119.7)	1.19 (145.4)

28. Secondary Outcome

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

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	Placebo
Arm/Group Description	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Participants were to take oral semaglutide placebo tablets once daily from week 0 to week 26.
Measure Participants	163	161
Normal (week 0) to normal (week 26)	38 23.3%	39 24.2%
Normal (week 0) to abnormal NCS (week 26)	13 8%	9 5.6%
Normal (week 0) to abnormal CS (week 26)	1 0.6%	0 0%
Abnormal (week 0) NCS to normal (week 26)	12 7.4%	13 8.1%
Abnormal (week 0) NCS to abnormal NCS (week 26)	84 51.5%	88 54.7%
Abnormal (week 0) NCS to abnormal CS (week 26)	1 0.6%	2 1.2%
Abnormal (week 0) CS to normal (week 26)	0 0%	0 0%
Abnormal (week 0) CS to abnormal NCS (week 26)	1 0.6%	0 0%
Abnormal (week 0) CS to abnormal CS (week 26)	4 2.5%	2 1.2%

29. Secondary Outcome

Title	Change in Physical Examination
Description	Participants with physical examination findings, normal, abnormal NCS and abnormal CS at baseline (week [wk] -2) and wk 26 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) Nervous system (central and peripheral); 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 26

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	Placebo
Arm/Group Description	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Participants were to take oral semaglutide placebo tablets once daily from week 0 to week 26.
Measure Participants	163	161
1) Cardiovascular system (wk -2): Normal	107 65.6%	103 64%
1) Cardiovascular system (wk -2): Abnormal NCS	50 30.7%	55 34.2%
1) Cardiovascular system (wk -2): Abnormal CS	6 3.7%	3 1.9%
1) Cardiovascular system (wk 26): Normal	101 62%	104 64.6%
1) Cardiovascular system (wk 26): Abnormal NCS	48 29.4%	47 29.2%
1) Cardiovascular system (wk 26): Abnormal CS	6 3.7%	3 1.9%
2) Nervous system (wk -2): Normal	114 69.9%	116 72%
2) Nervous system (wk -2): Abnormal NCS	41 25.2%	45 28%
2) Nervous system (wk -2): Abnormal CS	8 4.9%	0 0%
2) Nervous system (wk 26): Normal	109 66.9%	115 71.4%
2) Nervous system (wk 26): Abnormal NCS	40 24.5%	39 24.2%
2) Nervous system (wk 26): Abnormal CS	6 3.7%	0 0%
3) Gastrointestinal system (wk -2): Normal	149 91.4%	152 94.4%
3) Gastrointestinal system (wk -2): Abnormal NCS	14 8.6%	9 5.6%
3) Gastrointestinal system (wk -2): Abnormal CS	0 0%	0 0%
3) Gastrointestinal system (wk 26): Normal	146 89.6%	145 90.1%
3) Gastrointestinal system (wk 26): Abnormal NCS	9 5.5%	7 4.3%
3) Gastrointestinal system (wk 26): Abnormal CS	0 0%	1 0.6%
4) General appearance (wk -2): Normal	133 81.6%	138 85.7%
4) General appearance (wk -2): Abnormal NCS	27 16.6%	20 12.4%
4) General appearance (wk -2): Abnormal CS	3 1.8%	3 1.9%
4) General appearance (wk 26): Normal	139 85.3%	137 85.1%
4) General appearance (wk 26): Abnormal NCS	15 9.2%	16 9.9%
4) General appearance (wk 26): Abnormal CS	1 0.6%	1 0.6%
5) Head, throat, neck (wk -2): Normal	151 92.6%	143 88.8%
5) Head, throat, neck (wk -2): Abnormal NCS	10 6.1%	15 9.3%
5) Head, throat, neck (wk -2): Abnormal CS	2 1.2%	3 1.9%
5) Head, throat, neck (wk 26): Normal	142 87.1%	139 86.3%
5) Head, throat, neck (wk 26): Abnormal NCS	10 6.1%	11 6.8%
5) Head, throat, neck (wk 26): Abnormal CS	3 1.8%	3 1.9%
6) Lymph node palpation (wk -2): Normal	161 98.8%	161 100%
6) Lymph node palpation (wk -2): Abnormal NCS	1 0.6%	0 0%
6) Lymph node palpation (wk -2): Abnormal CS	0 0%	0 0%
6) Lymph node palpation (wk 26): Normal	155 95.1%	154 95.7%
6) Lymph node palpation (wk 26): Abnormal NCS	0 0%	0 0%
6) Lymph node palpation (wk 26): Abnormal CS	0 0%	0 0%
7) Musculoskeletal system (wk -2): Normal	131 80.4%	135 83.9%
7) Musculoskeletal system (wk -2): Abnormal NCS	27 16.6%	24 14.9%
7) Musculoskeletal system (wk -2): Abnormal CS	5 3.1%	2 1.2%
7) Musculoskeletal system (wk 26): Normal	131 80.4%	130 80.7%
7) Musculoskeletal system (wk 26): Abnormal NCS	22 13.5%	21 13%
7) Musculoskeletal system (wk 26): Abnormal CS	2 1.2%	2 1.2%
8) Respiratory system (wk -2): Normal	154 94.5%	150 93.2%
8) Respiratory system (wk -2): Abnormal NCS	9 5.5%	8 5%
8) Respiratory system (wk -2): Abnormal CS	0 0%	3 1.9%
8) Respiratory system (wk 26): Normal	151 92.6%	147 91.3%
8) Respiratory system (wk 26): Abnormal NCS	4 2.5%	5 3.1%
8) Respiratory system (wk 26): Abnormal CS	0 0%	2 1.2%
9) Skin (wk -2): Normal	129 79.1%	129 80.1%
9) Skin (wk -2): Abnormal NCS	33 20.2%	32 19.9%
9) Skin (wk -2): Abnormal CS	1 0.6%	0 0%
9) Skin (wk 26): Normal	128 78.5%	136 84.5%
9) Skin (wk 26): Abnormal NCS	23 14.1%	18 11.2%
9) Skin (wk 26): Abnormal CS	4 2.5%	0 0%
10) Thyroid gland (wk -2): Normal	150 92%	146 90.7%
10) Thyroid gland (wk -2): Abnormal NCS	12 7.4%	15 9.3%
10) Thyroid gland (wk -2): Abnormal CS	1 0.6%	0 0%
10) Thyroid gland (wk 26): Normal	142 87.1%	140 87%
10) Thyroid gland (wk 26): Abnormal NCS	12 7.4%	14 8.7%
10) Thyroid gland (wk 26): Abnormal CS	1 0.6%	0 0%

30. Secondary Outcome

Title	Change in Eye Examination
Description	Participants with eye examination findings, normal, abnormal NCS and abnormal CS at baseline (week -2) and week 26 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 26

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	Placebo
Arm/Group Description	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Participants were to take oral semaglutide placebo tablets once daily from week 0 to week 26.
Measure Participants	163	161
Left eye (week -2): Normal	57 35%	66 41%
Left eye (week -2): Abnormal NCS	98 60.1%	93 57.8%
Left eye (week -2): Abnormal CS	8 4.9%	0 0%
Left eye (week 26): Normal	54 33.1%	55 34.2%
Left eye (week 26): Abnormal NCS	92 56.4%	95 59%
Left eye (week 26): Abnormal CS	5 3.1%	0 0%
Right eye (week -2): Normal	59 36.2%	66 41%
Right eye (week -2): Abnormal NCS	97 59.5%	93 57.8%
Right eye (week -2): Abnormal CS	7 4.3%	0 0%
Right eye (week 26): Normal	52 31.9%	55 34.2%
Right eye (week 26): Abnormal NCS	97 59.5%	95 59%
Right eye (week 26): Abnormal CS	2 1.2%	0 0%

31. 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 0-31) 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 0-31

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 oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.
Measure Participants	162
Count of Participants [Participants]	1 0.6%

32. 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 0-31) 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 0-31

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 oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.
Measure Participants	162
Count of Participants [Participants]	0 0%

33. 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 0-31) 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 0-31

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 oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.
Measure Participants	162
Count of Participants [Participants]	1 0.6%

34. 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 0-31) 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 0-31

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 oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.
Measure Participants	162
Count of Participants [Participants]	0 0%

35. 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 0-31). 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 0-31

Outcome Measure Data

Analysis Population Description

Overall number of participants analysed = participants who were found positive for anti-semaglutide antibodies. As only one subject was analyzed, standard deviation could not be calculated.

Arm/Group Title	Oral Semaglutide 14 mg
Arm/Group Description	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.
Measure Participants	1
Week 4	3.1 (NA)
Week 31	2.2 (NA)

36. Secondary Outcome

Title	Semaglutide Plasma Concentrations for Population PK Analyses
Description	This outcome measure is only applicable for the oral semaglutide 14 mg treatment arm. Semaglutide plasma concentrations were measured at weeks 4, 8, 14 and 26. 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	Weeks 0-26

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
Arm/Group Description	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.
Measure Participants	163
Week 4	1.8 (113.5)
Week 8	5.2 (143.4)
Week 14	9.4 (206.6)
Week 26	6.9 (251.3)

37. Secondary Outcome

Title	SNAC Plasma Concentrations
Description	This outcome measure is only applicable for the oral semaglutide 14 mg treatment arm. Sodium N-[8-(2-hydroxybenzoyl) amino]caprylate (SNAC) plasma concentrations were measured after 25 and 40 minutes post-dose at weeks 4, 14 and 26. 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	Weeks 0-26

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
Arm/Group Description	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.
Measure Participants	163
Week 4: 25 minutes post-dose	578 (347.4)
Week 4: 40 minutes post-dose	364 (308.5)
Week 14: 25 minutes post-dose	418 (389.7)
Week 14: 40 minutes post-dose	330 (349.2)
Week 26: 25 minutes post-dose	435 (688.0)
Week 26: 40 minutes post-dose	288 (596.1)

38. Secondary Outcome

Title	Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS)
Description	SF-36 is a 36-item patient-reported survey of patient health that measures the participant's overall health-related quality of life (HRQoL). SF-36v2™ (acute version) questionnaire measured eight domains of functional health and well-being as well as two component summary scores (physical component summary (PCS) and mental component summary (MCS)). The 0-100 scale scores (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. In the metric of norm-based scores, 50 and 10 corresponds to the mean and standard deviation respectively of the 2009 U.S. general population. Change from baseline (week 0) in the domain scores and component summary (PCS and MCS) scores were evaluated at week 26. A positive change score indicates an improvement since baseline. Results are based on the data from the in-trial observation period.
Time Frame	Week 0, week 26

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	Placebo
Arm/Group Description	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Participants were to take oral semaglutide placebo tablets once daily from week 0 to week 26.
Measure Participants	163	161
1) Physical functioning	0.71 (7.21)	-0.41 (6.43)
2) Role functioning	1.97 (8.43)	-0.36 (7.76)
3) Bodily pain	3.18 (10.14)	-0.33 (11.47)
4) General health	0.18 (6.01)	-0.13 (5.77)
5) Vitality	0.05 (7.53)	0.56 (8.02)
6) Social functioning	1.87 (7.81)	-0.06 (9.64)
7) Role emotional	0.62 (10.83)	-1.18 (12.32)
8) Mental health	0.34 (8.72)	-0.19 (9.48)
Physical component summary (PCS)	1.78 (7.16)	-0.15 (6.10)
Mental component summary (MCS)	0.26 (8.74)	-0.32 (10.15)

39. Secondary Outcome

Title	Change in DTSQs: Individual Items and 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. 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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Oral Semaglutide 14 mg	Placebo
Arm/Group Description	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Participants were to take oral semaglutide placebo tablets once daily from week 0 to week 26.
Measure Participants	152	154
1) Satisfaction with treatment	0.41 (1.56)	0.74 (1.57)
2) Feeling of unacceptably high blood sugars	-1.26 (2.17)	-0.30 (2.08)
3) Feeling of unacceptably low blood sugars	0.11 (1.84)	-0.32 (1.82)
4) Convenience of treatment	0.43 (1.41)	0.42 (1.76)
5) Flexibility of treatment	0.37 (1.45)	0.52 (1.45)
6) Satisfaction with understanding of diabetes	0.31 (1.42)	0.60 (1.59)
7) Recommending treatment to others	0.71 (1.73)	0.37 (1.61)
8) Satisfaction to continue with present treatment	0.58 (1.84)	0.47 (1.87)
Total treatment satisfaction	2.82 (6.61)	3.13 (7.25)

40. Secondary Outcome

Title	Change in Urinalysis
Description	Participants with urinalysis, "leukocytes and erythrocytes" findings, negative, trace, small, moderate or large at baseline (week [wk] 0) and wk 26 are presented. Participants with urinalysis, "nitrit" findings, negative or positive at baseline (wk 0) and wk 26 are presented. 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 -2, week 26

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	Placebo
Arm/Group Description	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.	Participants were to take oral semaglutide placebo tablets once daily from week 0 to week 26.
Measure Participants	163	161
Leucocytes (wk 0): Negative	121 74.2%	122 75.8%
Leucocytes (wk 0): Trace	14 8.6%	7 4.3%
Leucocytes (wk 0): Small	8 4.9%	12 7.5%
Leucocytes (wk 0): Moderate	10 6.1%	9 5.6%
Leucocytes (wk 0): Large	5 3.1%	5 3.1%
Leucocytes (wk 26): Negative	91 55.8%	103 64%
Leucocytes (wk 26): Trace	9 5.5%	11 6.8%
Leucocytes (wk 26): Small	13 8%	10 6.2%
Leucocytes (wk 26): Moderate	10 6.1%	10 6.2%
Leucocytes (wk 26): Large	6 3.7%	4 2.5%
Erythrocytes (wk 0): Negative	147 90.2%	137 85.1%
Erythrocytes (wk 0): Trace	4 2.5%	10 6.2%
Erythrocytes (wk 0): Small	4 2.5%	4 2.5%
Erythrocytes (wk 0): Moderate	1 0.6%	1 0.6%
Erythrocytes (wk 0): Large	2 1.2%	3 1.9%
Erythrocytes (wk 26): Negative	115 70.6%	122 75.8%
Erythrocytes (wk 26): Trace	6 3.7%	7 4.3%
Erythrocytes (wk 26): Small	6 3.7%	3 1.9%
Erythrocytes (wk 26): Moderate	2 1.2%	4 2.5%
Erythrocytes (wk 26): Large	0 0%	2 1.2%
Nitrit (wk 0): Negative	149 91.4%	146 90.7%
Nitrit (wk 0): Positive	9 5.5%	9 5.6%
Nitrit (wk 26): Negative	118 72.4%	126 78.3%
Nitrit (wk 26): Positive	11 6.7%	12 7.5%

Adverse Events

Time Frame	Week 0 to week 31 (26 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		Placebo
Arm/Group Description	Participants were to take oral semaglutide tablets once daily in a dose escalation manner from week 0 to week 26: 3 mg from week 0 to week 4, 7 mg from week 4 to week 8 and 14 mg from week 8 to week 26.		Participants were to take oral semaglutide placebo tablets once daily from week 0 to week 26.
All Cause Mortality
	Oral Semaglutide 14 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/163 (0.6%)		2/161 (1.2%)
Serious Adverse Events
	Oral Semaglutide 14 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/163 (10.4%)		17/161 (10.6%)
Cardiac disorders
Acute myocardial infarction	2/163 (1.2%)	2	0/161 (0%)	0
Angina unstable	2/163 (1.2%)	2	0/161 (0%)	0
Atrial fibrillation	1/163 (0.6%)	1	1/161 (0.6%)	1
Coronary artery disease	1/163 (0.6%)	1	0/161 (0%)	0
Eye disorders
Eyelid ptosis	1/163 (0.6%)	1	0/161 (0%)	0
General disorders
Pyrexia	1/163 (0.6%)	1	0/161 (0%)	0
Sudden death	0/163 (0%)	0	1/161 (0.6%)	1
Infections and infestations
Arteriosclerotic gangrene	0/163 (0%)	0	1/161 (0.6%)	1
Biliary sepsis	1/163 (0.6%)	1	0/161 (0%)	0
Device related infection	0/163 (0%)	0	1/161 (0.6%)	1
Escherichia urinary tract infection	0/163 (0%)	0	1/161 (0.6%)	1
Gastroenteritis	1/163 (0.6%)	1	0/161 (0%)	0
Gastroenteritis bacterial	1/163 (0.6%)	1	0/161 (0%)	0
Infected bite	0/163 (0%)	0	1/161 (0.6%)	1
Injection site abscess	0/163 (0%)	0	1/161 (0.6%)	1
Postoperative wound infection	0/163 (0%)	0	1/161 (0.6%)	1
Sepsis	0/163 (0%)	0	1/161 (0.6%)	1
Urosepsis	0/163 (0%)	0	1/161 (0.6%)	1
Injury, poisoning and procedural complications
Animal bite	0/163 (0%)	0	1/161 (0.6%)	1
Limb crushing injury	1/163 (0.6%)	1	0/161 (0%)	0
Post procedural haemorrhage	1/163 (0.6%)	1	0/161 (0%)	0
Pubis fracture	0/163 (0%)	0	1/161 (0.6%)	1
Rib fracture	1/163 (0.6%)	1	0/161 (0%)	0
Spinal compression fracture	0/163 (0%)	0	1/161 (0.6%)	1
Vascular pseudoaneurysm	0/163 (0%)	0	1/161 (0.6%)	1
Metabolism and nutrition disorders
Gout	1/163 (0.6%)	1	0/161 (0%)	0
Musculoskeletal and connective tissue disorders
Flank pain	1/163 (0.6%)	1	0/161 (0%)	0
Muscular weakness	1/163 (0.6%)	1	0/161 (0%)	0
Musculoskeletal chest pain	1/163 (0.6%)	1	0/161 (0%)	0
Myalgia	0/163 (0%)	0	1/161 (0.6%)	1
Synovial cyst	0/163 (0%)	0	1/161 (0.6%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder transitional cell carcinoma	0/163 (0%)	0	1/161 (0.6%)	1
Invasive ductal breast carcinoma	0/163 (0%)	0	1/161 (0.6%)	1
Lung neoplasm malignant	1/163 (0.6%)	1	0/161 (0%)	0
Malignant melanoma in situ	1/163 (0.6%)	1	0/161 (0%)	0
Renal cell carcinoma	0/163 (0%)	0	1/161 (0.6%)	1
Nervous system disorders
Dysarthria	1/163 (0.6%)	1	0/161 (0%)	0
Haemorrhagic stroke	1/163 (0.6%)	1	0/161 (0%)	0
Ischaemic stroke	0/163 (0%)	0	1/161 (0.6%)	1
Transient global amnesia	1/163 (0.6%)	1	0/161 (0%)	0
Transient ischaemic attack	1/163 (0.6%)	1	0/161 (0%)	0
Psychiatric disorders
Confusional state	1/163 (0.6%)	1	0/161 (0%)	0
Renal and urinary disorders
Acute kidney injury	1/163 (0.6%)	1	1/161 (0.6%)	1
Nephrolithiasis	0/163 (0%)	0	1/161 (0.6%)	1
Renal impairment	0/163 (0%)	0	1/161 (0.6%)	1
Urinary retention	1/163 (0.6%)	1	0/161 (0%)	0
Respiratory, thoracic and mediastinal disorders
Respiratory failure	0/163 (0%)	0	1/161 (0.6%)	1
Vascular disorders
Hypertensive crisis	1/163 (0.6%)	1	0/161 (0%)	0
Other (Not Including Serious) Adverse Events
	Oral Semaglutide 14 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	75/163 (46%)		32/161 (19.9%)
Gastrointestinal disorders
Constipation	19/163 (11.7%)	23	6/161 (3.7%)	6
Diarrhoea	17/163 (10.4%)	24	6/161 (3.7%)	16
Dyspepsia	16/163 (9.8%)	20	2/161 (1.2%)	2
Nausea	31/163 (19%)	38	12/161 (7.5%)	12
Vomiting	19/163 (11.7%)	29	2/161 (1.2%)	2
Metabolism and nutrition disorders
Decreased appetite	11/163 (6.7%)	12	0/161 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	1/163 (0.6%)	1	9/161 (5.6%)	9
Nervous system disorders
Headache	10/163 (6.1%)	13	8/161 (5%)	21

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.