SUSTAIN 9: Efficacy and Safety of Semaglutide Once-weekly Versus Placebo as add-on to SGLT-2i in Subjects With Type 2 Diabetes Mellitus

Sponsor

Novo Nordisk A/S (Industry)

Overall Status

Completed

CT.gov ID

NCT03086330

Collaborator

(none)

302

Enrollment

Locations

Arms

16.7

Actual Duration (Months)

4.2

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This trial is conducted in Asia, Europe and North America. The aim of the trial is to compare the effect of semaglutide s.c. 1.0 mg once-weekly versus placebo as add-on to sodium glucose co-transporter-2 inhibitor (SGLT-2i) monotherapy or in combination with either metformin or sulfonylurea on glycaemic control after 30 weeks of treatment in subjects with type 2 diabetes. Subjects will remain on their pre-trial medication.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Diabetes Mellitus, Type 2	Drug: Semaglutide Drug: Placebo	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

302 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

Efficacy and Safety of Semaglutide Once-weekly Versus Placebo as add-on to SGLT-2i in Subjects With Type 2 Diabetes Mellitus. A 30-week Randomised, Double-blind, Placebo-controlled Trial

Actual Study Start Date :

Mar 15, 2017

Actual Primary Completion Date :

Jul 4, 2018

Actual Study Completion Date :

Aug 6, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Semaglutide	Drug: Semaglutide Semaglutide, gradually increased to 1.0 mg, injected once weekly under the skin (subcutaneously, s.c.) for 30 weeks
Placebo Comparator: Placebo	Drug: Placebo Semaglutide placebo, gradually increased to 1.0 mg, injected once weekly under the skin (subcutaneously, s.c.) for 30 weeks

Arm

Intervention/Treatment

Experimental: Semaglutide

Drug: Semaglutide

Semaglutide, gradually increased to 1.0 mg, injected once weekly under the skin (subcutaneously, s.c.) for 30 weeks

Placebo Comparator: Placebo

Drug: Placebo

Semaglutide placebo, gradually increased to 1.0 mg, injected once weekly under the skin (subcutaneously, s.c.) for 30 weeks

Outcome Measures

Primary Outcome Measures

Change in HbA1c [Week 0, week 30]
Change from baseline (week 0) in HbA1c was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose of trial product and ended at the first date of any of the following: 1) the last dose of trial product + 7 days or 2) initiation of rescue medication.

Secondary Outcome Measures

Change in Body Weight (kg) [Week 0, week 30]
Change from baseline (week 0) in body weight was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.
Change in Fasting Plasma Glucose (FPG) [Week 0, week 30]
Change from baseline (week 0) in FPG was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.
Change in Self-measured Plasma Glucose (SMPG), 7-point Profile: Mean 7-point Profile [Week 0, week 30]
Change from baseline (week 0) in mean of the SMPG, 7-point profile was evaluated at week 30. Mean 7-point profile (the area under the profile) was calculated using the trapezoidal method and divided by the measurement time. Results are based on the 'on-treatment without rescue medication' observation period. Participants measured their plasma glucose at 7 different time points: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner and at bedtime.
Change in Self-measured Plasma Glucose (SMPG), 7-point Profile: Mean Post Prandial Increment (Over All Meals) [Week 0, week 30]
Change from baseline (week 0) in mean post prandial increment (over all meals) in the SMPG, 7-point profile was evaluated at week 30. The mean increment over all meals was derived as the mean of all available meal increments. Results are based on the 'on-treatment without rescue medication' observation period.
Change in Fasting Blood Lipid, Total Cholesterol [Week 0, week 30]
Change from baseline (week 0) in total cholesterol (measured in mmol/L and presented as ratio to baseline) was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.
Change in Fasting Blood Lipid, Low-density Lipoprotein (LDL) Cholesterol [Week 0, week 30]
Change from baseline (week 0) in LDL (measured in mmol/L and presented as ratio to baseline) was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.
Change in Fasting Blood Lipid, High-density Lipoprotein (HDL) Cholesterol [Week 0, week 30]
Change from baseline (week 0) in HDL (measured in mmol/L and presented as ratio to baseline) was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.
Change in Fasting Blood Lipid, Triglycerides [Week 0, week 30]
Change from baseline (week 0) in triglycerides (measured in mmol/L and presented as ratio to baseline) was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.
Change in Body Weight (%) [Week 0, week 30]
Percent (%) change from baseline (week 0) in body weight (measured in kilogram (kg)) was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.
Change in Body Mass Index [Week 0, week 30]
Change from baseline (week 0) in body mass index (BMI) was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period. BMI was calculated as 'body weight in kg/(height in meters) x (height in meters)'.
Change in Waist Circumference [Week 0, week 30]
Change from baseline (week 0) in waist circumference was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.
Change in Systolic Blood Pressure [Week 0, week 30]
Change from baseline (week 0) in systolic blood pressure was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.
Change in Diastolic Blood Pressure [Week 0, week 30]
Change from baseline (week 0) in diastolic blood pressure was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.
Change in Scores for Selected Patient Reported Outcomes: Short-form Health Survey (SF-36v2TM): Total Scores (Physical Component and Mental Component) and Scores From the 8 Domains [Week 0, week 30]
Change from baseline (week 0) in patient reported outcome (PRO) questionnaire, SF-36v2TM was evaluated at week 30. The SF-36v2™ questionnaire was used to assess the overall health related quality of life of participants. This questionnaire contains 36 items and measures the individual overall health related quality of life on 8 domains: 1) Physical functioning, 2) Role functioning, 3) Bodily pain, 4) General health, 5) Vitality, 6) Social functioning, 7) Role emotional and 8) Mental health. Each item is scored on a scale from 1 to either 2, 3, 5, or 6; each item score is then converted to a scale of 0-100, representing the percentage of total possible score achieved and with higher scores indicating a higher health status; items on the same scale are then averaged to obtain the 8 scale scores. Physical component summary (PCS) includes domains 1-4 and mental component summary (MCS) includes domains 5-8. Higher PCS and MCS scores on a scale of 0-100 indicate a higher health status.
Change in Scores for Selected Patient Reported Outcomes: Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment Satisfaction Score (Sum of 6 of 8 Items) and the 8 Items Separately [Week 0, week 30]
Change from baseline (week 0) in PRO questionnaire, DTSQ was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period. The DTSQ measures satisfaction with diabetes treatment. The DTSQ consists of 8 items evaluating 6 aspects of treatment satisfaction and 2 perceived recent event rates of hyperglycemia/hypoglycemia. Each item is scored on a 7- point Likert scale ranging from 0 (very dissatisfied) to 6 (very satisfied). Items evaluating 6 aspects (items 3-8) of treatment satisfaction are summed to produce a total treatment satisfaction score; DTSQ status total scores range from 0-36, with higher scores indicating greater satisfaction; the perceived frequency of hyperglycemia/hypoglycemia items are scored separately, with lower scores indicating better perceived blood glucose control.
HbA1c Below 7.0% (53 mmol/Mol) [After 30 weeks]
Percentage of participants with HbA1c below 7.0% (53 mmol/mol) was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.
HbA1c Equal to or Below 6.5% (48 mmol/Mol) [After 30 weeks]
Percentage of participants with HbA1c equal to or below 6.5% (48 mmol/mol) was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.
Weight Loss Equal to or Above 3% [After 30 weeks]
Percentage of participants with weight loss equal to or above 3% of their baseline (week 0) body weight was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.
Weight Loss Equal to or Above 5% [After 30 weeks]
Percentage of participants with weight loss equal to or above 5% of their baseline (week 0) body weight was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.
Weight Loss Equal to or Above 10% [After 30 weeks]
Percentage of participants with weight loss equal to or above 10% of their baseline (week 0) body weight was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.
HbA1c Below 7.0% (53 mmol/Mol) Without Severe or BG Confirmed Symptomatic Hypoglycaemia Episodes and no Weight Gain [After 30 weeks]
Percentage of participants with HbA1c below 7.0% (53 mmol/mol) without severe or BG confirmed symptomatic hypoglycaemia episodes and no weight gain from their baseline (week 0) body weight was evaluated at week 30. Severe or blood glucose (BG)-confirmed symptomatic hypoglycaemia: an episode that was severe according to the American Diabetes Association (ADA) classification or confirmed by a plasma glucose (PG) value below 3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. Results are based on the 'on-treatment without rescue medication' observation period.
HbA1c Reduction Equal to or Above 1%-Point [After 30 weeks]
Percentage of participants with HbA1c reduction equal to or above 1%-point was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.
HbA1c Reduction Equal to or Above 1%-Point and Weight Loss Equal to or Above 3% [After 30 weeks]
Percentage of participants with HbA1c reduction equal to or above 1%-point and weight loss equal to or above 3% of their baseline (week 0) body weight was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.
HbA1c Reduction Equal to or Above 1%-Point and Weight Loss Equal to or Above 5% [After 30 weeks]
Percentage of participants with HbA1c reduction equal to or above 1%-point and weight loss equal to or above 5% of their baseline (week 0) body weight was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.
HbA1c Reduction Equal to or Above 1%-Point and Weight Loss Equal to or Above 10% [After 30 weeks]
Percentage of participants with HbA1c reduction equal to or above 1%-point and weight loss equal to or above 10% of their baseline (week 0) body weight was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.
Number of Treatment-emergent Adverse Events (TEAEs) [Week 0 - week 30]
A TEAE was defined as an event that has onset date (or increase in severity) during the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 42 days.
Number of Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes [Week 0 - week 30]
Hypoglycaemic episodes were defined as treatment emergent if the onset of the episode occurred within the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 42 days. Severe or BG-confirmed symptomatic hypoglycaemia: an episode that was severe according to the ADA classification or confirmed by a PG value below 3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.
Change in Haematology: Haemoglobin [Week 0, week 30]
Change from baseline (week 0) in haemoglobin was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Change in Haematology: Haematocrit [Week 0, week 30]
Change from baseline (week 0) in haematocrit was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Change in Haematology: Thrombocytes [Week 0, week 30]
Change from baseline (week 0) in thrombocytes was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Change in Haematology: Erythrocytes [Week 0, week 30]
Change from baseline (week 0) in erythrocytes was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Change in Haematology: Leucocytes [Week 0, week 30]
Change from baseline (week 0) in leucocytes was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Change in Biochemistry: Amylase [Week 0, week 30]
Change from baseline (week 0) in amylase was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Change in Biochemistry: Lipase [Week 0, week 30]
Change from baseline (week 0) in lipase was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Change in Biochemistry: Alkaline Phosphatase [Week 0, week 30]
Change from baseline (week 0) in alkaline phosphatase was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Change in Biochemistry: Alanine Aminotransferase [Week 0, week 30]
Change from baseline (week 0) in alanine aminotransferase was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Change in Biochemistry: Aspartate Aminotransferase [Week 0, week 30]
Change from baseline (week 0) in aspartate aminotransferase was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Change in Biochemistry: Total Bilirubin [Week 0, week 30]
Change from baseline (week 0) in total bilirubin was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Change in Biochemistry: Albumin [Week 0, week 30]
Change from baseline (week 0) in albumin was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Change in Biochemistry: Calcium (Total) [Week 0, week 30]
Change from baseline (week 0) in albumin was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Change in Biochemistry: Potassium [Week 0, week 30]
Change from baseline (week 0) in potassium was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Change in Biochemistry: Sodium [Week 0, week 30]
Change from baseline (week 0) in sodium was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Change in Biochemistry: Bicarbonate [Week 0, week 30]
Change from baseline (week 0) in bicarbonate was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Change in Biochemistry: Estimated Glomerular Filtration Rate (eGFR) [Week 0, week 30]
Change from baseline (week 0) in eGFR was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Change in Biochemistry: Creatinine [Week 0, week 30]
Change from baseline (week 0) in creatinine was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Change in Calcitonin [Week 0, week 30]
Change from baseline (week 0) in calcitonin was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Change in Pulse [Week 0, week 30]
Change from baseline (week 0) in pulse rate was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Change in Electrocardiogram [Week 0, week 30]
Electrocardiogram (ECG) results are presented for week 0 (baseline) and week 30. ECG finding are presented as percentage of participants with normal, abnormal non-clinically significant (NCS) and abnormal clinically significant (CS) ECG values. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 42 days.
Change in Physical Examination: General Appearance [Week -2, week 30]
Physical examination (general appearance) results are presented for week -2 (baseline) and week 30. Results are presented as percentage of participants with normal, abnormal NCS and abnormal CS findings. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Change in Physical Examination: Central and Peripheral Nervous System [Week -2, week 30]
Physical examination (central and peripheral nervous system) results are presented for week -2 (baseline) and week 30. Results are presented as percentage of participants with normal, abnormal NCS and abnormal CS findings. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Change in Physical Examination: Cardiovascular System [Week -2, week 30]
Physical examination (cardiovascular system) results are presented for week -2 (baseline) and week 30. Results are presented as percentage of participants with normal, abnormal NCS and abnormal CS findings. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Change in Physical Examination: Gastrointestinal System Including Mouth [Week -2, week 30]
Physical examination (gastrointestinal system including mouth) results are presented for week -2 (baseline) and week 30. Results are presented as percentage of participants with normal, abnormal NCS and abnormal CS findings. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Change in Physical Examination: Skin [Week -2, week 30]
Physical examination (skin) results are presented for week -2 (baseline) and week 30. Results are presented as percentage of participants with normal, abnormal NCS and abnormal CS findings. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Change in Physical Examination: Respiratory System [Week -2, week 30]
Physical examination (respiratory system) results are presented for week -2 (baseline) and week 30. Results are presented as percentage of participants with normal, abnormal NCS and abnormal CS findings. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Change in Physical Examination: Lymph Node Palpation [Week -2, week 30]
Physical examination (lymph node palpation) results are presented for week -2 (baseline) and week 30. Results are presented as percentage of participants with normal, abnormal NCS and abnormal CS findings. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Change in Physical Examination: Thyroid Gland [Week -2, week 30]
Physical examination (thyroid gland) results are presented for week -2 (baseline) and week 30. Results are presented as percentage of participants with normal, abnormal NCS and abnormal CS findings. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Change in Fundoscopy [Week 0, week 30]
Fundoscopy results for both left and right eyes are presented for week 0 (baseline) and week 30. Results are presented as percentage of participants with normal, abnormal NCS and abnormal CS findings. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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, above or equal to 18 years at the time of signing informed consent. For Japan only: Male or female, age equal to or above 20 years at the time of signing informed consent
Diagnosed with type 2 diabetes mellitus
HbA1c of 7.0-10.0% (53-86 mmol/mol) (both inclusive)
Stable dose of an SGLT-2 inhibitor as monotherapy or in combination (including fixed-dose drug combination) with a stable dose of metformin (equal to or above 1500 mg or maximum tolerated dose) or a SU for at least 90 days prior to the day of screening. All medications in compliance with current local label

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)
Any disorder which in the investigator's opinion might jeopardise subject's safety or compliance with the protocol
Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within the past 90 days prior to the day of screening. However, short term insulin treatment for a maximum of 14 days prior to the day of screening is allowed
Subjects with alanine aminotransferase above 2.5 x upper normal limit
Family or personal history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma. Family is defined as a first degree relative
History or presence of pancreatitis (acute or chronic)
History of diabetic ketoacidosis
Any of the following: myocardial infarction, stroke, hospitalization for unstable angina or transient ischaemic attack within the past 180 days prior to the day of screening
Subjects presently classified as being in New York Heart Association Class IV
Planned coronary, carotid or peripheral artery revascularisation known on the day of screening
Renal impairment measured as estimated Glomerular Filtration Rate value of eGFR below 60 ml/min/1.73 m^2 as defined by KDIGO 2012 classification using isotope dilution mass spectrometry for serum creatinine measured at screening
Proliferative retinopathy or maculopathy requiring acute treatment. Verified by fundus photography or dilated fundoscopy performed within the past 90 days prior to randomisation
Presence or history of malignant neoplasms within the past 5 years prior to the day of screening. Basal and squamous cell skin cancer and any carcinoma in-situ is allowed

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Andalusia	Alabama	United States	36420
2	Novo Nordisk Investigational Site	Anniston	Alabama	United States	36207
3	Novo Nordisk Investigational Site	Glendale	Arizona	United States	85308
4	Novo Nordisk Investigational Site	Phoenix	Arizona	United States	85037
5	Novo Nordisk Investigational Site	Tempe	Arizona	United States	85283
6	Novo Nordisk Investigational Site	Little Rock	Arkansas	United States	72211
7	Novo Nordisk Investigational Site	La Jolla	California	United States	92037
8	Novo Nordisk Investigational Site	Lincoln	California	United States	95648
9	Novo Nordisk Investigational Site	Northridge	California	United States	91325
10	Novo Nordisk Investigational Site	Edgewater	Florida	United States	32132
11	Novo Nordisk Investigational Site	Maitland	Florida	United States	32751-4422
12	Novo Nordisk Investigational Site	Lawrenceville	Georgia	United States	30046
13	Novo Nordisk Investigational Site	Woodstock	Georgia	United States	30189-4255
14	Novo Nordisk Investigational Site	Hutchinson	Kansas	United States	67502-1131
15	Novo Nordisk Investigational Site	Lexington	Kentucky	United States	40503
16	Novo Nordisk Investigational Site	Baltimore	Maryland	United States	21204
17	Novo Nordisk Investigational Site	Troy	Michigan	United States	48098
18	Novo Nordisk Investigational Site	Jefferson City	Missouri	United States	65109
19	Novo Nordisk Investigational Site	Albany	New York	United States	12206
20	Novo Nordisk Investigational Site	Smithtown	New York	United States	11787
21	Novo Nordisk Investigational Site	West Seneca	New York	United States	14224
22	Novo Nordisk Investigational Site	Charlotte	North Carolina	United States	28207
23	Novo Nordisk Investigational Site	Charlotte	North Carolina	United States	28226
24	Novo Nordisk Investigational Site	Gastonia	North Carolina	United States	28054
25	Novo Nordisk Investigational Site	Greenville	North Carolina	United States	27834
26	Novo Nordisk Investigational Site	Kinston	North Carolina	United States	28501
27	Novo Nordisk Investigational Site	Morehead City	North Carolina	United States	28557-4346
28	Novo Nordisk Investigational Site	Norman	Oklahoma	United States	73069
29	Novo Nordisk Investigational Site	Beaver	Pennsylvania	United States	15009
30	Novo Nordisk Investigational Site	McMurray	Pennsylvania	United States	15317
31	Novo Nordisk Investigational Site	Pittsburgh	Pennsylvania	United States	15243
32	Novo Nordisk Investigational Site	Arlington	Texas	United States	76012-4637
33	Novo Nordisk Investigational Site	Austin	Texas	United States	78745
34	Novo Nordisk Investigational Site	Dallas	Texas	United States	75208
35	Novo Nordisk Investigational Site	Dallas	Texas	United States	75231
36	Novo Nordisk Investigational Site	Houston	Texas	United States	77081
37	Novo Nordisk Investigational Site	Irving	Texas	United States	75061-2210
38	Novo Nordisk Investigational Site	Shavano Park	Texas	United States	78231
39	Novo Nordisk Investigational Site	Sugar Land	Texas	United States	77479
40	Novo Nordisk Investigational Site	Victoria	Texas	United States	77901
41	Novo Nordisk Investigational Site	Murray	Utah	United States	84123
42	Novo Nordisk Investigational Site	Chesapeake	Virginia	United States	23321
43	Novo Nordisk Investigational Site	Olympia	Washington	United States	98502
44	Novo Nordisk Investigational Site	Saint Stefan		Austria	8511
45	Novo Nordisk Investigational Site	Wien		Austria	1030
46	Novo Nordisk Investigational Site	Wien		Austria	1060
47	Novo Nordisk Investigational Site	Wien		Austria	1130
48	Novo Nordisk Investigational Site	Edmonton	Alberta	Canada	T6H 2L4
49	Novo Nordisk Investigational Site	Winnipeg	Manitoba	Canada	R3E 3P4
50	Novo Nordisk Investigational Site	Brampton	Ontario	Canada	L6S 0C6
51	Novo Nordisk Investigational Site	Brampton	Ontario	Canada	L6T 0G1
52	Novo Nordisk Investigational Site	Etobicoke	Ontario	Canada	M9R 4E1
53	Novo Nordisk Investigational Site	Smiths Falls	Ontario	Canada	K7A 4W8
54	Novo Nordisk Investigational Site	Toronto	Ontario	Canada	M5T 3L9
55	Novo Nordisk Investigational Site	Waterloo	Ontario	Canada	N2J 1C4
56	Novo Nordisk Investigational Site	Kanagawa		Japan	232-0064
57	Novo Nordisk Investigational Site	Nagakute-shi, Aichi		Japan	480-1195
58	Novo Nordisk Investigational Site	Suita-shi, Osaka		Japan	565-0853
59	Novo Nordisk Investigational Site	Tokyo		Japan	160-0008
60	Novo Nordisk Investigational Site	Hamar		Norway	2317
61	Novo Nordisk Investigational Site	Hoenefoss		Norway	3515
62	Novo Nordisk Investigational Site	Namsos		Norway	7801
63	Novo Nordisk Investigational Site	Olso		Norway	0953
64	Novo Nordisk Investigational Site	Oslo		Norway	0176
65	Novo Nordisk Investigational Site	Skedsmokorset		Norway	NO-2020
66	Novo Nordisk Investigational Site	Stavanger		Norway	4005
67	Novo Nordisk Investigational Site	Ponce		Puerto Rico	00716
68	Novo Nordisk Investigational Site	Barnaul		Russian Federation	656045
69	Novo Nordisk Investigational Site	Novosibirsk		Russian Federation	630099
70	Novo Nordisk Investigational Site	Saint-Petersburg		Russian Federation	191119
71	Novo Nordisk Investigational Site	Saint-Petersburg		Russian Federation	194358
72	Novo Nordisk Investigational Site	St. Petersburg		Russian Federation	194354

Sponsors and Collaborators

Novo Nordisk A/S

Investigators

None specified.

Study Documents (Full-Text)

Study Protocol and Statistical Analysis Plan - Feb 18, 2019

More Information

Publications

None provided.

Responsible Party:

Novo Nordisk A/S

ClinicalTrials.gov Identifier:

NCT03086330

Other Study ID Numbers:

NN9535-4269
2016-000904-27
U1111-1180-1213
JapicCTI-173542

First Posted:

Mar 22, 2017

Last Update Posted:

Jul 2, 2021

Last Verified:

Jul 1, 2021

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:

Additional relevant MeSH terms:

Diabetes Mellitus

Diabetes Mellitus, Type 2

Study Results

Participant Flow

Recruitment Details	The trial was conducted at 61 sites in 6 countries as follows: Austria (4 sites), Canada (8 sites), Japan (4 sites), Norway (4 sites), Russian Federation (5 sites), United States of America (USA) (36 sites). In addition, 1 site in Norway and 3 sites in the USA screened, but didn't randomise any participant.
Pre-assignment Detail

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as subcutaneous (s.c.) injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Period Title: Overall Study
STARTED	151	151
Exposed	150	151
COMPLETED	147	147
NOT COMPLETED	4	4

Baseline Characteristics

Arm/Group Title	Semaglutide 1.0 mg	Placebo	Total
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.	Total of all reporting groups
Overall Participants	151	151	302
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	57.5 (8.9)	56.6 (10.1)	57.0 (9.5)
Sex: Female, Male (Count of Participants)
Female	62 41.1%	64 42.4%	126 41.7%
Male	89 58.9%	87 57.6%	176 58.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	9 6%	13 8.6%	22 7.3%
Not Hispanic or Latino	142 94%	138 91.4%	280 92.7%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska native	2 1.3%	0 0%	2 0.7%
Asian	36 23.8%	35 23.2%	71 23.5%
Black or African American	9 6%	4 2.6%	13 4.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
White	100 66.2%	109 72.2%	209 69.2%
Other	4 2.6%	3 2%	7 2.3%
Glycosylated haemoglobin (HbA1c) (Percentage HbA1c) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percentage HbA1c]	8.0 (0.8)	8.1 (0.8)	8.0 (0.8)

Outcome Measures

1. Primary Outcome

Title	Change in HbA1c
Description	Change from baseline (week 0) in HbA1c was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period, which started at the date of first dose of trial product and ended at the first date of any of the following: 1) the last dose of trial product + 7 days or 2) initiation of rescue medication.
Time Frame	Week 0, week 30

Outcome Measure Data

Analysis Population Description
Full analysis set (FAS), which included all randomised participants. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	151	151
Mean (Standard Deviation) [Percentage of HbA1c]	-1.6 (0.8)	-0.2 (0.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Semaglutide 1.0 mg, Placebo
	Comments	The responses were analysed using an analysis of covariance (ANCOVA) with treatment, stratification factor and region as fixed factors and baseline value as covariate. Before analysis, missing data were multiple imputed using observed data from participants within the same group defined by randomised treatment, using a regression model including stratification factor and region as categorical effects and data from baseline and all previous visits as covariates.
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-1.42
	Confidence Interval	(2-Sided) 95% -1.61 to -1.24
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change in Body Weight (kg)
Description	Change from baseline (week 0) in body weight was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.
Time Frame	Week 0, week 30

Outcome Measure Data

Analysis Population Description
FAS which included all randomised participants. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	151	151
Mean (Standard Deviation) [Kg]	-4.7 (4.3)	-1.0 (3.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Semaglutide 1.0 mg, Placebo
	Comments	The responses were analysed using an ANCOVA with treatment, stratification factor and region as fixed factors and baseline value as covariate. Before analysis, missing data were multiple imputed using observed data from participants within the same group defined by randomised treatment, using a regression model including stratification factor and region as categorical effects and data from baseline and all previous visits as covariates.
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	ANCOVA
	Comments

Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-3.81
	Confidence Interval	(2-Sided) 95% -4.70 to -2.93
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change in Fasting Plasma Glucose (FPG)
Description	Change from baseline (week 0) in FPG was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.
Time Frame	Week 0, week 30

Outcome Measure Data

Analysis Population Description
FAS which included all randomised participants. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	151	151
Mean (Standard Deviation) [mmol/L]	-2.26 (2.05)	0.07 (2.07)

4. Secondary Outcome

Title	Change in Self-measured Plasma Glucose (SMPG), 7-point Profile: Mean 7-point Profile
Description	Change from baseline (week 0) in mean of the SMPG, 7-point profile was evaluated at week 30. Mean 7-point profile (the area under the profile) was calculated using the trapezoidal method and divided by the measurement time. Results are based on the 'on-treatment without rescue medication' observation period. Participants measured their plasma glucose at 7 different time points: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner and at bedtime.
Time Frame	Week 0, week 30

Outcome Measure Data

Analysis Population Description
FAS which included all randomised participants. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	151	151
Mean (Standard Deviation) [mmol/L]	-2.6 (1.9)	-0.3 (2.0)

5. Secondary Outcome

Title	Change in Self-measured Plasma Glucose (SMPG), 7-point Profile: Mean Post Prandial Increment (Over All Meals)
Description	Change from baseline (week 0) in mean post prandial increment (over all meals) in the SMPG, 7-point profile was evaluated at week 30. The mean increment over all meals was derived as the mean of all available meal increments. Results are based on the 'on-treatment without rescue medication' observation period.
Time Frame	Week 0, week 30

Outcome Measure Data

Analysis Population Description
FAS which included all randomised participants. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	151	151
Mean (Standard Deviation) [mmol/L]	-1.2 (2.0)	0.0 (2.2)

6. Secondary Outcome

Title	Change in Fasting Blood Lipid, Total Cholesterol
Description	Change from baseline (week 0) in total cholesterol (measured in mmol/L and presented as ratio to baseline) was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.
Time Frame	Week 0, week 30

Outcome Measure Data

Analysis Population Description
FAS which included all randomised participants. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	151	151
Geometric Mean (Geometric Coefficient of Variation) [Ratio]	0.91 (19.4)	1.02 (18.9)

7. Secondary Outcome

Title	Change in Fasting Blood Lipid, Low-density Lipoprotein (LDL) Cholesterol
Description	Change from baseline (week 0) in LDL (measured in mmol/L and presented as ratio to baseline) was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.
Time Frame	Week 0, week 30

Outcome Measure Data

Analysis Population Description
FAS which included all randomised participants. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	151	151
Geometric Mean (Geometric Coefficient of Variation) [Ratio]	0.90 (31.6)	1.04 (27.7)

8. Secondary Outcome

Title	Change in Fasting Blood Lipid, High-density Lipoprotein (HDL) Cholesterol
Description	Change from baseline (week 0) in HDL (measured in mmol/L and presented as ratio to baseline) was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.
Time Frame	Week 0, week 30

Outcome Measure Data

Analysis Population Description
FAS which included all randomised participants. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	151	151
Geometric Mean (Geometric Coefficient of Variation) [Ratio]	0.99 (15.8)	1.01 (13.9)

9. Secondary Outcome

Title	Change in Fasting Blood Lipid, Triglycerides
Description	Change from baseline (week 0) in triglycerides (measured in mmol/L and presented as ratio to baseline) was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.
Time Frame	Week 0, week 30

Outcome Measure Data

Analysis Population Description
FAS which included all randomised participants. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	151	151
Geometric Mean (Geometric Coefficient of Variation) [Ratio]	0.81 (41.3)	0.97 (38.7)

10. Secondary Outcome

Title	Change in Body Weight (%)
Description	Percent (%) change from baseline (week 0) in body weight (measured in kilogram (kg)) was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.
Time Frame	Week 0, week 30

Outcome Measure Data

Analysis Population Description
FAS which included all randomised participants. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	151	151
Mean (Standard Deviation) [Percentage]	-5.4 (4.8)	-1.0 (3.1)

11. Secondary Outcome

Title	Change in Body Mass Index
Description	Change from baseline (week 0) in body mass index (BMI) was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period. BMI was calculated as 'body weight in kg/(height in meters) x (height in meters)'.
Time Frame	Week 0, week 30

Outcome Measure Data

Analysis Population Description
FAS which included all randomised participants. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	151	151
Mean (Standard Deviation) [Kg/sqm]	-1.7 (1.5)	-0.4 (1.1)

12. Secondary Outcome

Title	Change in Waist Circumference
Description	Change from baseline (week 0) in waist circumference was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.
Time Frame	Week 0, week 30

Outcome Measure Data

Analysis Population Description
FAS which included all randomised participants. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	151	151
Mean (Standard Deviation) [cm]	-4.4 (5.5)	-1.8 (4.5)

13. Secondary Outcome

Title	Change in Systolic Blood Pressure
Description	Change from baseline (week 0) in systolic blood pressure was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.
Time Frame	Week 0, week 30

Outcome Measure Data

Analysis Population Description
FAS which included all randomised participants. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	151	151
Mean (Standard Deviation) [mmHg]	-4.3 (14.5)	1.1 (12.3)

14. Secondary Outcome

Title	Change in Diastolic Blood Pressure
Description	Change from baseline (week 0) in diastolic blood pressure was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.
Time Frame	Week 0, week 30

Outcome Measure Data

Analysis Population Description
FAS which included all randomised participants. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	151	151
Mean (Standard Deviation) [mmHg]	-0.1 (8.1)	-0.1 (6.7)

15. Secondary Outcome

Title	Change in Scores for Selected Patient Reported Outcomes: Short-form Health Survey (SF-36v2TM): Total Scores (Physical Component and Mental Component) and Scores From the 8 Domains
Description	Change from baseline (week 0) in patient reported outcome (PRO) questionnaire, SF-36v2TM was evaluated at week 30. The SF-36v2™ questionnaire was used to assess the overall health related quality of life of participants. This questionnaire contains 36 items and measures the individual overall health related quality of life on 8 domains: 1) Physical functioning, 2) Role functioning, 3) Bodily pain, 4) General health, 5) Vitality, 6) Social functioning, 7) Role emotional and 8) Mental health. Each item is scored on a scale from 1 to either 2, 3, 5, or 6; each item score is then converted to a scale of 0-100, representing the percentage of total possible score achieved and with higher scores indicating a higher health status; items on the same scale are then averaged to obtain the 8 scale scores. Physical component summary (PCS) includes domains 1-4 and mental component summary (MCS) includes domains 5-8. Higher PCS and MCS scores on a scale of 0-100 indicate a higher health status.
Time Frame	Week 0, week 30

Outcome Measure Data

Analysis Population Description
FAS which included all randomised participants. Number analyzed = number of participants with available data. Results are based on the 'on-treatment without rescue medication' observation period.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	151	151
Physical component summary	1.9 (4.9)	0.7 (5.4)
1) Physical functioning	1.3 (4.1)	1.1 (5.2)
2) Role functioning	1.5 (6.1)	0.0 (6.0)
3) Bodily pain	0.9 (7.4)	0.1 (8.1)
4) General health	2.7 (6.8)	0.1 (6.8)
Mental component summary	0.1 (5.6)	-0.9 (6.3)
5) Vitality	1.5 (6.2)	0.2 (6.7)
6) Social functioning	0.3 (7.3)	-1.0 (7.4)
7) Role emotional	0.1 (6.7)	-0.2 (7.5)
8) Mental health	0.5 (5.2)	-0.6 (6.0)

16. Secondary Outcome

Title	Change in Scores for Selected Patient Reported Outcomes: Diabetes Treatment Satisfaction Questionnaire (DTSQ): Treatment Satisfaction Score (Sum of 6 of 8 Items) and the 8 Items Separately
Description	Change from baseline (week 0) in PRO questionnaire, DTSQ was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period. The DTSQ measures satisfaction with diabetes treatment. The DTSQ consists of 8 items evaluating 6 aspects of treatment satisfaction and 2 perceived recent event rates of hyperglycemia/hypoglycemia. Each item is scored on a 7- point Likert scale ranging from 0 (very dissatisfied) to 6 (very satisfied). Items evaluating 6 aspects (items 3-8) of treatment satisfaction are summed to produce a total treatment satisfaction score; DTSQ status total scores range from 0-36, with higher scores indicating greater satisfaction; the perceived frequency of hyperglycemia/hypoglycemia items are scored separately, with lower scores indicating better perceived blood glucose control.
Time Frame	Week 0, week 30

Outcome Measure Data

Analysis Population Description
FAS which included all randomised participants. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	151	151
1) Feeling of unacceptably high blood sugars	-2.2 (1.9)	-0.8 (2.2)
2) Feeling of unacceptably low blood sugars	0.3 (1.5)	-0.4 (1.5)
Total treatment satisfaction score (Sum of 3-8)	4.2 (6.6)	1.9 (7.0)
3) Satisfaction with current treatment	0.8 (1.6)	0.2 (1.4)
4) Convenience of current treatment	0.7 (1.3)	0.5 (1.3)
5) Flexibility of current treatment	0.7 (1.5)	0.4 (1.7)
6) Satisfaction with understanding of diabetes	0.5 (1.2)	0.5 (1.5)
7) Recommending treatment to others	0.8 (1.3)	0.2 (1.8)
8) Satisfaction to continue with present treatment	0.8 (1.7)	0.2 (1.7)

17. Secondary Outcome

Title	HbA1c Below 7.0% (53 mmol/Mol)
Description	Percentage of participants with HbA1c below 7.0% (53 mmol/mol) was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.
Time Frame	After 30 weeks

Outcome Measure Data

Analysis Population Description
FAS which included all randomised participants. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	120	127
Number [Percentage of participants]	82.5 54.6%	20.5 13.6%

18. Secondary Outcome

Title	HbA1c Equal to or Below 6.5% (48 mmol/Mol)
Description	Percentage of participants with HbA1c equal to or below 6.5% (48 mmol/mol) was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.
Time Frame	After 30 weeks

Outcome Measure Data

Analysis Population Description
FAS which included all randomised participants. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	120	127
Number [Percentage of participants]	60.0 39.7%	3.9 2.6%

19. Secondary Outcome

Title	Weight Loss Equal to or Above 3%
Description	Percentage of participants with weight loss equal to or above 3% of their baseline (week 0) body weight was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.
Time Frame	After 30 weeks

Outcome Measure Data

Analysis Population Description
FAS which included all randomised participants. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	121	128
Number [Percentage of participants]	69.4 46%	21.1 14%

20. Secondary Outcome

Title	Weight Loss Equal to or Above 5%
Description	Percentage of participants with weight loss equal to or above 5% of their baseline (week 0) body weight was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.
Time Frame	After 30 weeks

Outcome Measure Data

Analysis Population Description
FAS which included all randomised participants. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	121	128
Number [Percentage of participants]	50.4 33.4%	7.8 5.2%

21. Secondary Outcome

Title	Weight Loss Equal to or Above 10%
Description	Percentage of participants with weight loss equal to or above 10% of their baseline (week 0) body weight was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.
Time Frame	After 30 weeks

Outcome Measure Data

Analysis Population Description
FAS which included all randomised participants. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	121	128
Number [Percentage of participants]	15.7 10.4%	1.6 1.1%

22. Secondary Outcome

Title	HbA1c Below 7.0% (53 mmol/Mol) Without Severe or BG Confirmed Symptomatic Hypoglycaemia Episodes and no Weight Gain
Description	Percentage of participants with HbA1c below 7.0% (53 mmol/mol) without severe or BG confirmed symptomatic hypoglycaemia episodes and no weight gain from their baseline (week 0) body weight was evaluated at week 30. Severe or blood glucose (BG)-confirmed symptomatic hypoglycaemia: an episode that was severe according to the American Diabetes Association (ADA) classification or confirmed by a plasma glucose (PG) value below 3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. Results are based on the 'on-treatment without rescue medication' observation period.
Time Frame	After 30 weeks

Outcome Measure Data

Analysis Population Description
FAS which included all randomised participants. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	120	127
Number [Percentage of participants]	72.5 48%	17.3 11.5%

23. Secondary Outcome

Title	HbA1c Reduction Equal to or Above 1%-Point
Description	Percentage of participants with HbA1c reduction equal to or above 1%-point was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.
Time Frame	After 30 weeks

Outcome Measure Data

Analysis Population Description
FAS which included all randomised participants. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	120	127
Number [Percentage of participants]	80.8 53.5%	15.0 9.9%

24. Secondary Outcome

Title	HbA1c Reduction Equal to or Above 1%-Point and Weight Loss Equal to or Above 3%
Description	Percentage of participants with HbA1c reduction equal to or above 1%-point and weight loss equal to or above 3% of their baseline (week 0) body weight was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.
Time Frame	After 30 weeks

Outcome Measure Data

Analysis Population Description
FAS which included all randomised participants. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	120	127
Number [Percentage of participants]	56.7 37.5%	7.9 5.2%

25. Secondary Outcome

Title	HbA1c Reduction Equal to or Above 1%-Point and Weight Loss Equal to or Above 5%
Description	Percentage of participants with HbA1c reduction equal to or above 1%-point and weight loss equal to or above 5% of their baseline (week 0) body weight was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.
Time Frame	After 30 weeks

Outcome Measure Data

Analysis Population Description
FAS which included all randomised participants. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	120	127
Number [Percentage of participants]	41.7 27.6%	4.7 3.1%

26. Secondary Outcome

Title	HbA1c Reduction Equal to or Above 1%-Point and Weight Loss Equal to or Above 10%
Description	Percentage of participants with HbA1c reduction equal to or above 1%-point and weight loss equal to or above 10% of their baseline (week 0) body weight was evaluated at week 30. Results are based on the 'on-treatment without rescue medication' observation period.
Time Frame	After 30 weeks

Outcome Measure Data

Analysis Population Description
FAS which included all randomised participants. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	120	127
Number [Percentage of participants]	15.0 9.9%	1.6 1.1%

27. Secondary Outcome

Title	Number of Treatment-emergent Adverse Events (TEAEs)
Description	A TEAE was defined as an event that has onset date (or increase in severity) during the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 42 days.
Time Frame	Week 0 - week 30

Outcome Measure Data

Analysis Population Description
Safety analysis set (SAS), which included all participants exposed to at least one dose of trial product (semaglutide or placebo).

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	150	151
Number [Events]	356	247

28. Secondary Outcome

Title	Number of Treatment Emergent Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes
Description	Hypoglycaemic episodes were defined as treatment emergent if the onset of the episode occurred within the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 42 days. Severe or BG-confirmed symptomatic hypoglycaemia: an episode that was severe according to the ADA classification or confirmed by a PG value below 3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia.
Time Frame	Week 0 - week 30

Outcome Measure Data

Analysis Population Description
SAS, which included all participants exposed to at least one dose of trial product.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	150	151
Number [Episodes]	4	0

29. Secondary Outcome

Title	Change in Haematology: Haemoglobin
Description	Change from baseline (week 0) in haemoglobin was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Time Frame	Week 0, week 30

Outcome Measure Data

Analysis Population Description
SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	150	151
Geometric Mean (Geometric Coefficient of Variation) [mmol/L]	1.1 (22.1)	1.1 (29.3)

30. Secondary Outcome

Title	Change in Haematology: Haematocrit
Description	Change from baseline (week 0) in haematocrit was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Time Frame	Week 0, week 30

Outcome Measure Data

Analysis Population Description
SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	150	151
Geometric Mean (Geometric Coefficient of Variation) [% of red blood cells]	1.4 (130.3)	1.1 (155.1)

31. Secondary Outcome

Title	Change in Haematology: Thrombocytes
Description	Change from baseline (week 0) in thrombocytes was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Time Frame	Week 0, week 30

Outcome Measure Data

Analysis Population Description
SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	150	151
Geometric Mean (Geometric Coefficient of Variation) [10^9 thrombocytes/L]	25.3 (94.9)	20.2 (100.7)

32. Secondary Outcome

Title	Change in Haematology: Erythrocytes
Description	Change from baseline (week 0) in erythrocytes was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Time Frame	Week 0, week 30

Outcome Measure Data

Analysis Population Description
SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	150	151
Geometric Mean (Geometric Coefficient of Variation) [10^12 erythrocytes/L]	0.16 (111.0)	0.11 (168.3)

33. Secondary Outcome

Title	Change in Haematology: Leucocytes
Description	Change from baseline (week 0) in leucocytes was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Time Frame	Week 0, week 30

Outcome Measure Data

Analysis Population Description
SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	150	151
Geometric Mean (Geometric Coefficient of Variation) [10^9 leucocytes/L]	0.65 (186.6)	0.54 (146.8)

34. Secondary Outcome

Title	Change in Biochemistry: Amylase
Description	Change from baseline (week 0) in amylase was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Time Frame	Week 0, week 30

Outcome Measure Data

Analysis Population Description
SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	150	151
Geometric Mean (Geometric Coefficient of Variation) [U/L]	10.2 (113.8)	5.0 (121.7)

35. Secondary Outcome

Title	Change in Biochemistry: Lipase
Description	Change from baseline (week 0) in lipase was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Time Frame	Week 0, week 30

Outcome Measure Data

Analysis Population Description
SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	150	151
Geometric Mean (Geometric Coefficient of Variation) [U/L]	11.6 (140.2)	4.5 (171.8)

36. Secondary Outcome

Title	Change in Biochemistry: Alkaline Phosphatase
Description	Change from baseline (week 0) in alkaline phosphatase was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Time Frame	Week 0, week 30

Outcome Measure Data

Analysis Population Description
SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	150	151
Geometric Mean (Geometric Coefficient of Variation) [U/L]	4.6 (171.2)	7.2 (106.7)

37. Secondary Outcome

Title	Change in Biochemistry: Alanine Aminotransferase
Description	Change from baseline (week 0) in alanine aminotransferase was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Time Frame	Week 0, week 30

Outcome Measure Data

Analysis Population Description
SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	150	151
Geometric Mean (Geometric Coefficient of Variation) [U/L]	4.5 (123.2)	4.8 (166.7)

38. Secondary Outcome

Title	Change in Biochemistry: Aspartate Aminotransferase
Description	Change from baseline (week 0) in aspartate aminotransferase was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Time Frame	Week 0, week 30

Outcome Measure Data

Analysis Population Description
SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	150	151
Geometric Mean (Geometric Coefficient of Variation) [U/L]	3.4 (112.3)	3.5 (90.1)

39. Secondary Outcome

Title	Change in Biochemistry: Total Bilirubin
Description	Change from baseline (week 0) in total bilirubin was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Time Frame	Week 0, week 30

Outcome Measure Data

Analysis Population Description
SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	150	151
Geometric Mean (Geometric Coefficient of Variation) [umol/L]	2.3 (128.1)	1.7 (134.8)

40. Secondary Outcome

Title	Change in Biochemistry: Albumin
Description	Change from baseline (week 0) in albumin was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Time Frame	Week 0, week 30

Outcome Measure Data

Analysis Population Description
SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	150	151
Geometric Mean (Geometric Coefficient of Variation) [g/dL]	0.1 (45.4)	0.1 (48.6)

41. Secondary Outcome

Title	Change in Biochemistry: Calcium (Total)
Description	Change from baseline (week 0) in albumin was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Time Frame	Week 0, week 30

Outcome Measure Data

Analysis Population Description
SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	150	151
Geometric Mean (Geometric Coefficient of Variation) [mmol/L]	0.04 (125.0)	0.05 (88.9)

42. Secondary Outcome

Title	Change in Biochemistry: Potassium
Description	Change from baseline (week 0) in potassium was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Time Frame	Week 0, week 30

Outcome Measure Data

Analysis Population Description
SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	150	151
Geometric Mean (Geometric Coefficient of Variation) [mmol/L]	0.3 (89.5)	0.2 (73.7)

43. Secondary Outcome

Title	Change in Biochemistry: Sodium
Description	Change from baseline (week 0) in sodium was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Time Frame	Week 0, week 30

Outcome Measure Data

Analysis Population Description
SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	150	151
Geometric Mean (Geometric Coefficient of Variation) [mmol/L]	1.7 (55.8)	1.5 (48.4)

44. Secondary Outcome

Title	Change in Biochemistry: Bicarbonate
Description	Change from baseline (week 0) in bicarbonate was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Time Frame	Week 0, week 30

Outcome Measure Data

Analysis Population Description
SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	150	151
Geometric Mean (Geometric Coefficient of Variation) [mmol/L]	2.2 (67.6)	2.1 (69.0)

45. Secondary Outcome

Title	Change in Biochemistry: Estimated Glomerular Filtration Rate (eGFR)
Description	Change from baseline (week 0) in eGFR was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Time Frame	Week 0, week 30

Outcome Measure Data

Analysis Population Description
SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	150	151
Geometric Mean (Geometric Coefficient of Variation) [mL/min/1.73m2]	3.4 (114.8)	3.2 (105.6)

46. Secondary Outcome

Title	Change in Biochemistry: Creatinine
Description	Change from baseline (week 0) in creatinine was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Time Frame	Week 0, week 30

Outcome Measure Data

Analysis Population Description
SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	150	151
Geometric Mean (Geometric Coefficient of Variation) [umol/L]	4.6 (118.8)	2.6 (191.5)

47. Secondary Outcome

Title	Change in Calcitonin
Description	Change from baseline (week 0) in calcitonin was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Time Frame	Week 0, week 30

Outcome Measure Data

Analysis Population Description
SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	150	151
Geometric Mean (Geometric Coefficient of Variation) [ng/L]	1.3 (172.1)	1.7 (171.1)

48. Secondary Outcome

Title	Change in Pulse
Description	Change from baseline (week 0) in pulse rate was evaluated at week 30. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Time Frame	Week 0, week 30

Outcome Measure Data

Analysis Population Description
SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	150	151
Mean (Standard Deviation) [beats/min]	4.0 (9.6)	0.1 (8.4)

49. Secondary Outcome

Title	Change in Electrocardiogram
Description	Electrocardiogram (ECG) results are presented for week 0 (baseline) and week 30. ECG finding are presented as percentage of participants with normal, abnormal non-clinically significant (NCS) and abnormal clinically significant (CS) ECG values. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 42 days.
Time Frame	Week 0, week 30

Outcome Measure Data

Analysis Population Description
SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	150	151
Week 0: Normal	62.4 41.3%	66.2 43.8%
Week 0: Abnormal, NCS	36.9 24.4%	32.5 21.5%
Week 0: Abnormal, CS	0.7 0.5%	1.3 0.9%
Week 30: Normal	64.3 42.6%	66.4 44%
Week 30: Abnormal, NCS	34.9 23.1%	32.2 21.3%
Week 30: Abnormal, CS	0.8 0.5%	1.4 0.9%

50. Secondary Outcome

Title	Change in Physical Examination: General Appearance
Description	Physical examination (general appearance) results are presented for week -2 (baseline) and week 30. Results are presented as percentage of participants with normal, abnormal NCS and abnormal CS findings. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Time Frame	Week -2, week 30

Outcome Measure Data

Analysis Population Description
SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	150	151
Week -2: Normal	90.0 59.6%	86.0 57%
Week -2: Abnormal, NCS	10.0 6.6%	14.0 9.3%
Week -2: Abnormal, CS	0 0%	0 0%
Week 30: Normal	87.6 58%	87.1 57.7%
Week 30: Abnormal, NCS	11.6 7.7%	12.2 8.1%
Week 30: Abnormal, CS	0.8 0.5%	0.7 0.5%

51. Secondary Outcome

Title	Change in Physical Examination: Central and Peripheral Nervous System
Description	Physical examination (central and peripheral nervous system) results are presented for week -2 (baseline) and week 30. Results are presented as percentage of participants with normal, abnormal NCS and abnormal CS findings. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Time Frame	Week -2, week 30

Outcome Measure Data

Analysis Population Description
SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	150	151
Week -2: Normal	92.0 60.9%	86.7 57.4%
Week -2: Abnormal, NCS	7.3 4.8%	12.7 8.4%
Week -2: Abnormal, CS	0.7 0.5%	0.7 0.5%
Week 30: Normal	94.2 62.4%	87.8 58.1%
Week 30: Abnormal, NCS	5.0 3.3%	12.2 8.1%
Week 30: Abnormal, CS	0.8 0.5%	0 0%

52. Secondary Outcome

Title	Change in Physical Examination: Cardiovascular System
Description	Physical examination (cardiovascular system) results are presented for week -2 (baseline) and week 30. Results are presented as percentage of participants with normal, abnormal NCS and abnormal CS findings. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Time Frame	Week -2, week 30

Outcome Measure Data

Analysis Population Description
SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	150	151
Week -2: Normal	98.7 65.4%	93.3 61.8%
Week -2: Abnormal, NCS	1.3 0.9%	6.0 4%
Week -2: Abnormal, CS	0 0%	0.7 0.5%
Week 30: Normal	98.3 65.1%	92.8 61.5%
Week 30: Abnormal, NCS	1.7 1.1%	7.2 4.8%
Week 30: Abnormal, CS	0 0%	0 0%

53. Secondary Outcome

Title	Change in Physical Examination: Gastrointestinal System Including Mouth
Description	Physical examination (gastrointestinal system including mouth) results are presented for week -2 (baseline) and week 30. Results are presented as percentage of participants with normal, abnormal NCS and abnormal CS findings. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Time Frame	Week -2, week 30

Outcome Measure Data

Analysis Population Description
SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	150	151
Week -2: Normal	93.3 61.8%	93.3 61.8%
Week -2: Abnormal, NCS	6.7 4.4%	6.7 4.4%
Week -2: Abnormal, CS	0 0%	0 0%
Week 30: Normal	95.9 63.5%	94.2 62.4%
Week 30: Abnormal, NCS	3.3 2.2%	5.8 3.8%
Week 30: Abnormal, CS	0.8 0.5%	0 0%

54. Secondary Outcome

Title	Change in Physical Examination: Skin
Description	Physical examination (skin) results are presented for week -2 (baseline) and week 30. Results are presented as percentage of participants with normal, abnormal NCS and abnormal CS findings. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Time Frame	Week -2, week 30

Outcome Measure Data

Analysis Population Description
SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	150	151
Week -2: Normal	91.3 60.5%	93.3 61.8%
Week -2: Abnormal, NCS	8.7 5.8%	6.7 4.4%
Week -2: Abnormal, CS	0 0%	0 0%
Week 30: Normal	93.4 61.9%	95.0 62.9%
Week 30: Abnormal, NCS	6.6 4.4%	4.3 2.8%
Week 30: Abnormal, CS	0 0%	0.7 0.5%

55. Secondary Outcome

Title	Change in Physical Examination: Respiratory System
Description	Physical examination (respiratory system) results are presented for week -2 (baseline) and week 30. Results are presented as percentage of participants with normal, abnormal NCS and abnormal CS findings. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Time Frame	Week -2, week 30

Outcome Measure Data

Analysis Population Description
SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	150	151
Week -2: Normal	100 66.2%	98.7 65.4%
Week -2: Abnormal, NCS	0 0%	1.3 0.9%
Week -2: Abnormal, CS	0 0%	0 0%
Week 30: Normal	100 66.2%	99.3 65.8%
Week 30: Abnormal, NCS	0 0%	0.7 0.5%
Week 30: Abnormal, CS	0 0%	0 0%

56. Secondary Outcome

Title	Change in Physical Examination: Lymph Node Palpation
Description	Physical examination (lymph node palpation) results are presented for week -2 (baseline) and week 30. Results are presented as percentage of participants with normal, abnormal NCS and abnormal CS findings. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Time Frame	Week -2, week 30

Outcome Measure Data

Analysis Population Description
SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	150	151
Week -2: Normal	99.3 65.8%	100 66.2%
Week -2: Abnormal, NCS	0.7 0.5%	0 0%
Week -2: Abnormal, CS	0 0%	0 0%
Week 30: Normal	99.2 65.7%	100 66.2%
Week 30: Abnormal, NCS	0 0%	0 0%
Week 30: Abnormal, CS	0.8 0.5%	0 0%

57. Secondary Outcome

Title	Change in Physical Examination: Thyroid Gland
Description	Physical examination (thyroid gland) results are presented for week -2 (baseline) and week 30. Results are presented as percentage of participants with normal, abnormal NCS and abnormal CS findings. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Time Frame	Week -2, week 30

Outcome Measure Data

Analysis Population Description
SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	150	151
Week -2: Normal	98.0 64.9%	96.7 64%
Week -2: Abnormal, NCS	2.0 1.3%	3.3 2.2%
Week -2: Abnormal, CS	0 0%	0 0%
Week 30: Normal	99.2 65.7%	97.1 64.3%
Week 30: Abnormal, NCS	0.8 0.5%	2.9 1.9%
Week 30: Abnormal, CS	0 0%	0 0%

58. Secondary Outcome

Title	Change in Fundoscopy
Description	Fundoscopy results for both left and right eyes are presented for week 0 (baseline) and week 30. Results are presented as percentage of participants with normal, abnormal NCS and abnormal CS findings. Results are based on the on-treatment observation period, which started at the date of first dose of trial product and ended at the last date on trial product + 7 days.
Time Frame	Week 0, week 30

Outcome Measure Data

Analysis Population Description
SAS which included all participants exposed to at least one dose of trial product. Number analyzed = number of participants with available data.

Arm/Group Title	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.	Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
Measure Participants	150	151
Left eye: Week 0; normal	70.7 46.8%	62.0 41.1%
Left eye: Week 0; abnormal, NCS	24.7 16.4%	32.7 21.7%
Left eye: Week 0; abnormal, CS	4.7 3.1%	5.3 3.5%
Left eye: Week 30; normal	79.3 52.5%	64.1 42.5%
Left eye: Week 30; abnormal, NCS	17.1 11.3%	31.5 20.9%
Left eye: Week 30; abnormal, CS	3.7 2.5%	4.3 2.8%
Right eye: Week 0; normal	69.3 45.9%	62.4 41.3%
Right eye: Week 0; abnormal, NCS	25.3 16.8%	30.9 20.5%
Right eye: Week 0; abnormal, CS	5.3 3.5%	6.7 4.4%
Right eye: Week 30; normal	75.6 50.1%	63.7 42.2%
Right eye: Week 30; abnormal, NCS	19.5 12.9%	31.9 21.1%
Right eye: Week 30; abnormal, CS	4.9 3.2%	4.4 2.9%

Adverse Events

	Semaglutide 1.0 mg		Placebo
Time Frame	Week 0 to week 30 (treatment period) + 42 days (follow-up period). All the reported adverse events (AEs) are TEAEs.
Adverse Event Reporting Description	Results are based on the SAS. Treatment with semaglutide or placebo followed a fixed dose escalation. The maintenance dose of semaglutide 1.0 mg was reached after 4 doses (4 weeks) of 0.25 mg, followed by 4 doses (4 weeks) of 0.5 mg. The same fixed dose escalation scheme was followed for placebo, with respective dose matching volume. Hence, the adverse events are combinedly presented under 2 respective reporting groups, 'semaglutide 1.0 mg and placebo'.

Arm/Group Title	Semaglutide 1.0 mg		Placebo
Arm/Group Description	Participants received semaglutide in a dose escalation manner for 30 weeks: 0.25 mg (weeks 1 to 4), 0.50 mg (weeks 5 to 8) and 1.0 mg (weeks 9 to 30). Semaglutide was taken once weekly as s.c. injections.		Participants received matching placebo (for semaglutide) in a dose escalation manner for 30 weeks. Placebo was taken once weekly as s.c. injections. Dose escalation for placebo matched that for semaglutide with regards to volume.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/150 (0%)		0/151 (0%)
Serious Adverse Events
	Semaglutide 1.0 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/150 (4.7%)		6/151 (4%)
Cardiac disorders
Angina unstable	1/150 (0.7%)	1	0/151 (0%)	0
Coronary artery disease	1/150 (0.7%)	1	0/151 (0%)	0
Eye disorders
Retinal artery occlusion	1/150 (0.7%)	1	0/151 (0%)	0
Gastrointestinal disorders
Colitis ischaemic	1/150 (0.7%)	1	0/151 (0%)	0
Infections and infestations
Gastroenteritis bacterial	0/150 (0%)	0	1/151 (0.7%)	1
Neurocysticercosis	1/150 (0.7%)	1	0/151 (0%)	0
Injury, poisoning and procedural complications
Accidental overdose	1/150 (0.7%)	1	0/151 (0%)	0
Ankle fracture	0/150 (0%)	0	1/151 (0.7%)	1
Lower limb fracture	0/150 (0%)	0	1/151 (0.7%)	1
Musculoskeletal and connective tissue disorders
Osteoarthritis	0/150 (0%)	0	1/151 (0.7%)	1
Osteonecrosis	0/150 (0%)	0	1/151 (0.7%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Laryngeal squamous cell carcinoma	0/150 (0%)	0	1/151 (0.7%)	1
Nervous system disorders
Transient ischaemic attack	1/150 (0.7%)	2	0/151 (0%)	0
Renal and urinary disorders
Acute kidney injury	1/150 (0.7%)	1	0/151 (0%)	0
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	1/150 (0.7%)	3	0/151 (0%)	0
Surgical and medical procedures
Thyroidectomy	1/150 (0.7%)	1	0/151 (0%)	0
Other (Not Including Serious) Adverse Events
	Semaglutide 1.0 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	49/150 (32.7%)		28/151 (18.5%)
Eye disorders
Diabetic retinopathy	2/150 (1.3%)	2	8/151 (5.3%)	9
Gastrointestinal disorders
Constipation	10/150 (6.7%)	10	0/151 (0%)	0
Diarrhoea	17/150 (11.3%)	21	9/151 (6%)	11
Nausea	29/150 (19.3%)	37	5/151 (3.3%)	7
Vomiting	14/150 (9.3%)	21	3/151 (2%)	3
Infections and infestations
Nasopharyngitis	8/150 (5.3%)	9	8/151 (5.3%)	11

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.

Results Point of Contact

Name/Title	Clinical Reporting Anchor and Disclosure (1452)
Organization	Novo Nordisk A/S
Phone	(+1) 866-867-7178
Email	clinicaltrials@novonordisk.com

Responsible Party:

Novo Nordisk A/S

ClinicalTrials.gov Identifier:

NCT03086330

Other Study ID Numbers:

NN9535-4269
2016-000904-27
U1111-1180-1213
JapicCTI-173542

First Posted:

Mar 22, 2017

Last Update Posted:

Jul 2, 2021

Last Verified:

Jul 1, 2021