SUSTAIN™1: Efficacy and Safety of Semaglutide Once-weekly Versus Placebo in Drug-naïve Subjects With Type 2 Diabetes

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02054897
• Collaborator: (none)
• Enrollment: 388
• Locations: 86
• Arms: 4
• Actual Duration (Months): 15.1
• Patients Per Site: 4.5
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This trial is conducted globally. The aim of this trial is to investigate efficacy and safety of semaglutide once-weekly versus placebo in drug-naïve subjects with type 2 diabetes. (SUSTAIN™ 1-Monotherapy).

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 388 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 in Drug-naïve Subjects With Type 2 Diabetes
• Actual Study Start Date: Feb 3, 2014
• Actual Primary Completion Date: May 8, 2015
• Actual Study Completion Date: May 8, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Semaglutide 1.0 mg	Drug: semaglutide; Once weekly, administrated subcutaneously (s.c. under the skin)
Experimental: Semaglutide 0.5 mg	Drug: semaglutide; Once weekly, administrated subcutaneously (s.c. under the skin)
Placebo Comparator: Semaglutide placebo 1.0 mg	Drug: placebo; Once weekly, administrated subcutaneously (s.c. under the skin)
Placebo Comparator: Semaglutide placebo 0.5 mg	Drug: placebo; Once weekly, administrated subcutaneously (s.c. under the skin)

Outcome Measures

Primary Outcome Measures

1. Change in HbA1c (Glycosylated Haemoglobin) [Week 0, week 30]

   Change from baseline (week 0) in HbA1c was evaluated after 30 weeks of treatment. Missing data were imputed from a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit.

Secondary Outcome Measures

1. Change in Body Weight [Week 0, week 30]

   Change from baseline (week 0) in body weight was evaluated after 30 weeks of treatment. Missing data were imputed from a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit.

2. Change in Fasting Plasma Glucose (FPG) [Week 0, week 30]

   Change from baseline (week 0) in FPG was evaluated after 30 weeks of treatment. Missing data were imputed from a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit.

3. Change in Systolic and Diastolic Blood Pressure [Week 0, week 30]

   Change from baseline (week 0) in systolic and diastolic blood pressure was evaluated after 30 weeks of treatment. Missing data were imputed from a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit.

4. Subjects Who Achieve (Yes/no):HbA1c Below 7.0% (53 mmol/Mol) American Diabetes Association Target [At 30 weeks of treatment]

   Percentage of subjects who achieve (yes/no): HbA1c below 7.0% (53 mmol/mol) American Diabetes Association target after 30 weeks' treatment. Missing HbA1c data imputed from a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit.

5. Subjects Who Achieve (Yes/no):HbA1c Below or Equal to 6.5% (48 mmol/Mol) American Association of Clinical Endocrinologists Target [At 30 weeks of treatment]

   Percentage of subjects who achieve (yes/no): HbA1c below 6.5% (48 mmol/mol) American Diabetes Association target after 30 weeks' treatment. Missing HbA1c data imputed from a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit.

Eligibility Criteria

Criteria

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

Inclusion Criteria: - For Japan only: Male or female, age above or equal to 20 years at the time of signing inform consent - Subjects diagnosed with type 2 diabetes and treated with diet and exercise for at least 30 days before screening - HbA1c 7.0 - 10.0 % (53 - 86 mmol/mol) (both inclusive) Exclusion Criteria: - Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using adequate contraceptive method (adequate contraceptive measures as required by local regulation or practice) throughout the trial including the 5 week follow-up period. United Kingdom: Adequate contraceptive measures are defined as established use of oral, injected or implanted hormonal methods of contraception, placement of an intrauterine device or intrauterine system, barrier methods of contraception (condom or occlusive cap with spermicidal foam/gel/film/cream/suppository), male sterilisation (where partner is sole partner of subject), or true abstinence (when in line with preferred and usual lifestyle) - Any chronic disorder or severe disease which, in the opinion of the investigator, might jeopardise subject's safety or compliance with the protocol - Treatment with any glucose lowering agent(s) in a period of 90 days prior to screening. An exception is short-term treatment (no longer than 7 days in total) with insulin in connection with inter-current illness - History of chronic or idiopathic acute pancreatitis - Screening calcitonin value above or equal to 50 ng/L (pg/mL) - Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 (MEN 2) - Impaired renal function defined as eGFR (estimated glomerular filtration rate ) below 30 mL/min/1.73 m^2 per modification of diet in renal disease (MDRD) formula (4 variable version) - Acute coronary or cerebrovascular event within 90 days before randomisation - Heart failure, New York Heart Association class IV

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Anniston	Alabama	United States	36207
2	Novo Nordisk Investigational Site	Birmingham	Alabama	United States	35216
3	Novo Nordisk Investigational Site	Pell City	Alabama	United States	35128
4	Novo Nordisk Investigational Site	Hawaiian Gardens	California	United States	90716
5	Novo Nordisk Investigational Site	Lomita	California	United States	90717
6	Novo Nordisk Investigational Site	Los Angeles	California	United States	90057
7	Novo Nordisk Investigational Site	Montclair	California	United States	91763
8	Novo Nordisk Investigational Site	Northridge	California	United States	91324
9	Novo Nordisk Investigational Site	Colorado Springs	Colorado	United States	80920
10	Novo Nordisk Investigational Site	Boynton Beach	Florida	United States	33472
11	Novo Nordisk Investigational Site	Jacksonville	Florida	United States	32277
12	Novo Nordisk Investigational Site	Miami Lakes	Florida	United States	33016
13	Novo Nordisk Investigational Site	Miami	Florida	United States	33015
14	Novo Nordisk Investigational Site	Miami	Florida	United States	33143
15	Novo Nordisk Investigational Site	Miami	Florida	United States	33144
16	Novo Nordisk Investigational Site	Miami	Florida	United States	33173
17	Novo Nordisk Investigational Site	Miami	Florida	United States	33174
18	Novo Nordisk Investigational Site	Pembroke Pines	Florida	United States	33026
19	Novo Nordisk Investigational Site	Savannah	Georgia	United States	31406
20	Novo Nordisk Investigational Site	Brownsburg	Indiana	United States	46112
21	Novo Nordisk Investigational Site	Franklin	Indiana	United States	46131
22	Novo Nordisk Investigational Site	Wichita	Kansas	United States	67226
23	Novo Nordisk Investigational Site	Lexington	Kentucky	United States	40504
24	Novo Nordisk Investigational Site	Olive Branch	Mississippi	United States	38654
25	Novo Nordisk Investigational Site	Billings	Montana	United States	59101
26	Novo Nordisk Investigational Site	Omaha	Nebraska	United States	68144
27	Novo Nordisk Investigational Site	Belvidere	New Jersey	United States	07823
28	Novo Nordisk Investigational Site	Albuquerque	New Mexico	United States	87102
29	Novo Nordisk Investigational Site	Charlotte	North Carolina	United States	28277
30	Novo Nordisk Investigational Site	Whiteville	North Carolina	United States	28472
31	Novo Nordisk Investigational Site	Cincinnati	Ohio	United States	45255
32	Novo Nordisk Investigational Site	Delaware	Ohio	United States	43015
33	Novo Nordisk Investigational Site	Levittown	Pennsylvania	United States	19056
34	Novo Nordisk Investigational Site	Spartanburg	South Carolina	United States	29303
35	Novo Nordisk Investigational Site	Dallas	Texas	United States	75230
36	Novo Nordisk Investigational Site	Sealy	Texas	United States	77474
37	Novo Nordisk Investigational Site	Sugar Land	Texas	United States	77478
38	Novo Nordisk Investigational Site	Sugar Land	Texas	United States	77479
39	Novo Nordisk Investigational Site	Vancouver	British Columbia	Canada	V6J 1S3
40	Novo Nordisk Investigational Site	Winnipeg	Manitoba	Canada	R2V 4W3
41	Novo Nordisk Investigational Site	London	Ontario	Canada	N6P 1A9
42	Novo Nordisk Investigational Site	Toronto	Ontario	Canada	M3J 1N2
43	Novo Nordisk Investigational Site	Montreal	Quebec	Canada	H4A 3T2
44	Novo Nordisk Investigational Site	Pointe-Claire	Quebec	Canada	H9R 4S3
45	Novo Nordisk Investigational Site	Trois Rivières	Quebec	Canada	G8T 7A1
46	Novo Nordisk Investigational Site	Catania		Italy	95122
47	Novo Nordisk Investigational Site	Pisa		Italy	56124
48	Novo Nordisk Investigational Site	Roma		Italy	00133
49	Novo Nordisk Investigational Site	Rome		Italy	00168
50	Novo Nordisk Investigational Site	Siena		Italy	53100
51	Novo Nordisk Investigational Site	Terni		Italy	05100
52	Novo Nordisk Investigational Site	Kyoto-shi, Kyoto		Japan	606-8507
53	Novo Nordisk Investigational Site	Suita-shi, Osaka		Japan	565-0853
54	Novo Nordisk Investigational Site	Tokyo		Japan	103-0027
55	Novo Nordisk Investigational Site	Tokyo		Japan	103-0028
56	Novo Nordisk Investigational Site	Tokyo		Japan	160-0008
57	Novo Nordisk Investigational Site	Monterrey	Nuevo León	Mexico	64620
58	Novo Nordisk Investigational Site	Ciudad Madero	Tamaulipas	Mexico	89440
59	Novo Nordisk Investigational Site	Aguascalientes		Mexico	20230
60	Novo Nordisk Investigational Site	Oradea	Bihor	Romania	410469
61	Novo Nordisk Investigational Site	Bucharest		Romania	010507
62	Novo Nordisk Investigational Site	Bucharest		Romania	13682
63	Novo Nordisk Investigational Site	Buzau		Romania	120203
64	Novo Nordisk Investigational Site	Galati		Romania	800578
65	Novo Nordisk Investigational Site	Arkhangelsk		Russian Federation	163001
66	Novo Nordisk Investigational Site	Arkhangelsk		Russian Federation	163045
67	Novo Nordisk Investigational Site	Chelyabinsk		Russian Federation	454048
68	Novo Nordisk Investigational Site	Kazan		Russian Federation	420073
69	Novo Nordisk Investigational Site	Novosibirsk		Russian Federation	630047
70	Novo Nordisk Investigational Site	Saint-Petersburg		Russian Federation	194358
71	Novo Nordisk Investigational Site	Saint-Petesburg		Russian Federation	195257
72	Novo Nordisk Investigational Site	Saratov		Russian Federation	410053
73	Novo Nordisk Investigational Site	Stavropol		Russian Federation	355035
74	Novo Nordisk Investigational Site	Port Elizabeth	Eastern Cape	South Africa	6014
75	Novo Nordisk Investigational Site	Bloemfontein	Free State	South Africa	9301
76	Novo Nordisk Investigational Site	Johannesburg	Gauteng	South Africa	1818
77	Novo Nordisk Investigational Site	Johannesburg	Gauteng	South Africa	1827
78	Novo Nordisk Investigational Site	Krugersdorp	Gauteng	South Africa	1739
79	Novo Nordisk Investigational Site	Pretoria	Gauteng	South Africa	0084
80	Novo Nordisk Investigational Site	Sophiatown	Gauteng	South Africa	2129
81	Novo Nordisk Investigational Site	Durban	KwaZulu-Natal	South Africa	4450
82	Novo Nordisk Investigational Site	Umkomaas	KwaZulu-Natal	South Africa	4170
83	Novo Nordisk Investigational Site	Cardiff		United Kingdom	CF5 4AD
84	Novo Nordisk Investigational Site	Dundee		United Kingdom	DD2 5NH
85	Novo Nordisk Investigational Site	St Helens		United Kingdom	WA9 3DA
86	Novo Nordisk Investigational Site	Swansea		United Kingdom	SA2 8PP

Sponsors and Collaborators

• Novo Nordisk A/S

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Clinical Trials at Novo Nordisk

Publications

• Fonseca VA, Capehorn MS, Garg SK, Jódar Gimeno E, Hansen OH, Holst AG, Nayak G, Seufert J. Reductions in insulin resistance are mediated primarily via weight loss in subjects with type 2 diabetes on semaglutide. J Clin Endocrinol Metab. 2019 Apr 2. pii: jc.2018-02685. doi: 10.1210/jc.2018-02685. [Epub ahead of print] Erratum in: J Clin Endocrinol Metab. 2020 Jan 1;105(1):.
• Overgaard RV, Lindberg SØ, Thielke D. Impact on HbA1c and body weight of switching from other GLP-1 receptor agonists to semaglutide: A model-based approach. Diabetes Obes Metab. 2019 Jan;21(1):43-51. doi: 10.1111/dom.13479. Epub 2018 Aug 23.
• Rodbard HW, Bellary S, Hramiak I, Seino Y, Silver R, Damgaard LH, Nayak G, Zacho J, Aroda VR. GREATER COMBINED REDUCTIONS IN HbA(1C) ≥1.0% AND WEIGHT ≥5.0% WITH SEMAGLUTIDE VERSUS COMPARATORS IN TYPE 2 DIABETES. Endocr Pract. 2019 Jun;25(6):589-597. doi: 10.4158/EP-2018-0444. Epub 2019 Mar 13.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT02054897
• Other Study ID Numbers: NN9535-3623; 2013-000632-94; U1111-1139-3090; JapicCTI-142442
• First Posted: Feb 4, 2014
• Last Update Posted: Jun 12, 2019
• Last Verified: May 1, 2019

• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2

Study Results

Participant Flow

Recruitment Details	Out of 87 sites, selected for recruitment, 72 sites in 8 countries randomised subjects: Canada: 7 sites; Italy: 6 sites; Japan: 5 sites; Mexico: 2 sites; Russian Federation: 8 sites; South Africa: 8 sites; United Kingdom: 4 sites; United States: 32 sites.

Arm/Group Title	Semaglutide 0.5 mg	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Subjects were given 0.25 mg semaglutide once weekly subcutaneous (s.c.; under the skin) injections for 4 weeks followed by 0.5 mg semaglutide once weekly for the remaining 26 weeks of the treatment period.	Subjects were given 0.25 mg semaglutide once weekly s.c. injection for 4 weeks, 0.5 mg semaglutide once weekly s.c. injections for the next 4 weeks followed by 1.0 mg semaglutide once weekly s.c. injections for the remaining 22 weeks of the treatment period.	Subjects were randomised to either of the 2 placebo arms (i.e., semaglutide placebo 0.5 mg and semaglutide placebo 1.0 mg) and then pooled for data analysis. Placebo 0.5 mg arm: Subjects were given 0.25 mg placebo once weekly s.c. injections for 4 weeks followed by 0.5 mg placebo once weekly s.c. injections for the remaining 26 weeks of the treatment period. Placebo 1.0 mg arm: Subjects were given 0.25 mg placebo once weekly s.c. injections for 4 weeks, 0.5 mg placebo once weekly s.c. injections for the next 4 weeks followed by 1.0 mg placebo once weekly s.c. injections for the remaining 22 weeks of the treatment period.
Period Title: Overall Study
STARTED	129	130	129
Exposed	128	130	129
COMPLETED	119	123	117
NOT COMPLETED	10	7	12

Baseline Characteristics

Arm/Group Title	Semaglutide 0.5 mg	Semaglutide 1.0 mg	Placebo	Total
Arm/Group Description	Subjects were given 0.25 mg semaglutide once weekly s.c. injection for 4 weeks followed by 0.5 mg semaglutide once weekly s.c. injections for the remaining 26 weeks of the treatment period.	Subjects were given 0.25 mg semaglutide once weekly s.c. injection for 4 weeks, 0.5 mg semaglutide once weekly s.c. injections for the next 4 weeks followed by 1.0 mg semaglutide once weekly s.c. injections for the remaining 22 weeks of the treatment period.	Subjects were randomised to either of the 2 placebo arms (i.e., semaglutide placebo 0.5 mg and semaglutide placebo 1.0 mg) and then pooled for data analysis. Placebo 0.5 mg arm: Subjects were given 0.25 mg placebo once weekly s.c. injections for 4 weeks followed by 0.5 mg placebo once weekly s.c. injections for the remaining 26 weeks of the treatment period. Placebo 1.0 mg arm: Subjects were given 0.25 mg placebo once weekly s.c. injections for 4 weeks, 0.5 mg placebo once weekly s.c. injections for the next 4 weeks followed by 1.0 mg placebo once weekly s.c. injections for the remaining 22 weeks of the treatment period.	Total of all reporting groups
Overall Participants	128	130	129	387
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	54.6 (11.1)	52.7 (11.9)	53.9 (11.0)	53.7 (11.3)
Sex: Female, Male (Count of Participants)
Female	68 53.1%	50 38.5%	59 45.7%	177 45.7%
Male	60 46.9%	80 61.5%	70 54.3%	210 54.3%
Glycosylated haemoglobin (HbA1c) (percentage of HbA1c) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [percentage of HbA1c]	8.09 (0.89)	8.12 (0.81)	7.95 (0.85)	8.05 (0.85)
Fasting plasma glucose (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	9.66 (2.77)	9.90 (2.50)	9.68 (2.77)	9.75 (2.67)
Body weight (kilogram(s)) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kilogram(s)]	89.81 (22.96)	96.87 (25.59)	89.05 (22.16)	91.93 (23.83)
Diastolic blood pressure (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	79.52 (9.06)	79.25 (8.52)	79.14 (8.39)	79.30 (8.64)
Systolic blood pressure (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	127.87 (13.15)	128.89 (12.92)	129.57 (13.50)	128.78 (13.18)

Outcome Measures

1. Primary Outcome

Title	Change in HbA1c (Glycosylated Haemoglobin)
Description	Change from baseline (week 0) in HbA1c was evaluated after 30 weeks of treatment. Missing data were imputed from a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit.
Time Frame	Week 0, week 30

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Semaglutide 0.5 mg	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Subjects were given 0.25 mg semaglutide once weekly s.c. injection for 4 weeks followed by 0.5 mg semaglutide once weekly s.c. injections for the remaining 26 weeks of the treatment period.	Subjects were given 0.25 mg semaglutide once weekly s.c. injection for 4 weeks, 0.5 mg semaglutide once weekly s.c. injections for the next 4 weeks followed by 1.0 mg semaglutide once weekly s.c. injections for the remaining 22 weeks of the treatment period.	Subjects were randomised to either of the 2 placebo arms (i.e., semaglutide placebo 0.5 mg and semaglutide placebo 1.0 mg) and then pooled for data analysis. Placebo 0.5 mg arm: Subjects were given 0.25 mg placebo once weekly s.c. injections for 4 weeks followed by 0.5 mg placebo once weekly s.c. injections for the remaining 26 weeks of the treatment period. Placebo 1.0 mg arm: Subjects were given 0.25 mg placebo once weekly s.c. injections for 4 weeks, 0.5 mg placebo once weekly s.c. injections for the next 4 weeks followed by 1.0 mg placebo once weekly s.c. injections for the remaining 22 weeks of the treatment period.
Measure Participants	128	130	129
Mean (Standard Deviation) [Percentage of HbA1c]	-1.47 (1.02)	-1.56 (1.26)	-0.00 (0.90)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Semaglutide 1.0 mg, Placebo
	Comments	For the primary HbA1c endpoint, superiority was planned to be tested for semaglutide 1.0 mg versus placebo. The post-baseline responses were analysed using a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit.
	Type of Statistical Test	Superiority
	Comments	Superiority for change in HbA1c was claimed if the upper limit of the 2-sided 95% confidence interval (CI) for the estimated difference was below 0%.
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-1.53
	Confidence Interval	(2-Sided) 95%; -1.81 to -1.25
	Parameter Dispersion	Type: Value:
	Estimation Comments	Semaglutide 1.0 mg minus Placebo

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Semaglutide 0.5 mg, Placebo
	Comments	For the primary HbA1c endpoint, superiority was planned to be tested for semaglutide 0.5 mg versus placebo, if superiority for semaglutide 1.0 mg was concluded. The post-baseline responses were analysed using a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit.
	Type of Statistical Test	Superiority
	Comments	Superiority for change in HbA1c was claimed if the upper limit of the 2-sided 95% CI for the estimated difference was below 0%.
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Treatment difference
	Estimated Value	-1.43
	Confidence Interval	(2-Sided) 95%; -1.71 to -1.15
	Parameter Dispersion	Type: Value:
	Estimation Comments	Semaglutide 0.5 mg minus Placebo

2. Secondary Outcome

Title	Change in Body Weight
Description	Change from baseline (week 0) in body weight was evaluated after 30 weeks of treatment. Missing data were imputed from a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit.
Time Frame	Week 0, week 30

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Semaglutide 0.5 mg	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Subjects were given 0.25 mg semaglutide once weekly s.c. injection for 4 weeks followed by 0.5 mg semaglutide once weekly s.c. injections for the remaining 26 weeks of the treatment period.	Subjects were given 0.25 mg semaglutide once weekly s.c. injection for 4 weeks, 0.5 mg semaglutide once weekly s.c. injections for the next 4 weeks followed by 1.0 mg semaglutide once weekly s.c. injections for the remaining 22 weeks of the treatment period.	Subjects were randomised to either of the 2 placebo arms (i.e., semaglutide placebo 0.5 mg and semaglutide placebo 1.0 mg) and then pooled for data analysis. Placebo 0.5 mg arm: Subjects were given 0.25 mg placebo once weekly s.c. injections for 4 weeks followed by 0.5 mg placebo once weekly s.c. injections for the remaining 26 weeks of the treatment period. Placebo 1.0 mg arm: Subjects were given 0.25 mg placebo once weekly s.c. injections for 4 weeks, 0.5 mg placebo once weekly s.c. injections for the next 4 weeks followed by 1.0 mg placebo once weekly s.c. injections for the remaining 22 weeks of the treatment period.
Measure Participants	128	130	129
Mean (Standard Deviation) [kilogram(s)]	-3.68 (4.03)	-4.67 (5.19)	-0.89 (3.46)

3. Secondary Outcome

Title	Change in Fasting Plasma Glucose (FPG)
Description	Change from baseline (week 0) in FPG was evaluated after 30 weeks of treatment. Missing data were imputed from a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit.
Time Frame	Week 0, week 30

Outcome Measure Data

Analysis Population Description

Full analysis set. Number of subject analysed=subjects who contributed to the analysis.

Arm/Group Title	Semaglutide 0.5 mg	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Subjects were given 0.25 mg semaglutide once weekly s.c. injection for 4 weeks followed by 0.5 mg semaglutide once weekly s.c. injections for the remaining 26 weeks of the treatment period.	Subjects were given 0.25 mg semaglutide once weekly s.c. injection for 4 weeks, 0.5 mg semaglutide once weekly s.c. injections for the next 4 weeks followed by 1.0 mg semaglutide once weekly s.c. injections for the remaining 22 weeks of the treatment period.	Subjects were randomised to either of the 2 placebo arms (i.e., semaglutide placebo 0.5 mg and semaglutide placebo 1.0 mg) and then pooled for data analysis. Placebo 0.5 mg arm: Subjects were given 0.25 mg placebo once weekly s.c. injections for 4 weeks followed by 0.5 mg placebo once weekly s.c. injections for the remaining 26 weeks of the treatment period. Placebo 1.0 mg arm: Subjects were given 0.25 mg placebo once weekly s.c. injections for 4 weeks, 0.5 mg placebo once weekly s.c. injections for the next 4 weeks followed by 1.0 mg placebo once weekly s.c. injections for the remaining 22 weeks of the treatment period.
Measure Participants	125	129	127
Mean (Standard Deviation) [mmol/L]	-2.41 (2.55)	-2.39 (2.74)	-0.55 (2.2)

4. Secondary Outcome

Title	Change in Systolic and Diastolic Blood Pressure
Description	Change from baseline (week 0) in systolic and diastolic blood pressure was evaluated after 30 weeks of treatment. Missing data were imputed from a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit.
Time Frame	Week 0, week 30

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Semaglutide 0.5 mg	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Subjects were given 0.25 mg semaglutide once weekly s.c. injection for 4 weeks followed by 0.5 mg semaglutide once weekly s.c. injections for the remaining 26 weeks of the treatment period.	Subjects were given 0.25 mg semaglutide once weekly s.c. injection for 4 weeks, 0.5 mg semaglutide once weekly s.c. injections for the next 4 weeks followed by 1.0 mg semaglutide once weekly s.c. injections for the remaining 22 weeks of the treatment period.	Subjects were randomised to either of the 2 placebo arms (i.e., semaglutide placebo 0.5 mg and semaglutide placebo 1.0 mg) and then pooled for data analysis. Placebo 0.5 mg arm: Subjects were given 0.25 mg placebo once weekly s.c. injections for 4 weeks followed by 0.5 mg placebo once weekly s.c. injections for the remaining 26 weeks of the treatment period. Placebo 1.0 mg arm: Subjects were given 0.25 mg placebo once weekly s.c. injections for 4 weeks, 0.5 mg placebo once weekly s.c. injections for the next 4 weeks followed by 1.0 mg placebo once weekly s.c. injections for the remaining 22 weeks of the treatment period.
Measure Participants	128	130	129
Systolic blood pressure	-2.29 (12.58)	-2.74 (11.58)	-2.01 (11.23)
Diastolic blood pressure	-0.73 (6.88)	0.22 (7.6)	0.60 (7.59)

5. Secondary Outcome

Title	Subjects Who Achieve (Yes/no):HbA1c Below 7.0% (53 mmol/Mol) American Diabetes Association Target
Description	Percentage of subjects who achieve (yes/no): HbA1c below 7.0% (53 mmol/mol) American Diabetes Association target after 30 weeks' treatment. Missing HbA1c data imputed from a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit.
Time Frame	At 30 weeks of treatment

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Semaglutide 0.5 mg	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Subjects were given 0.25 mg semaglutide once weekly s.c. injection for 4 weeks followed by 0.5 mg semaglutide once weekly s.c. injections for the remaining 26 weeks of the treatment period.	Subjects were given 0.25 mg semaglutide once weekly s.c. injection for 4 weeks, 0.5 mg semaglutide once weekly s.c. injections for the next 4 weeks followed by 1.0 mg semaglutide once weekly s.c. injections for the remaining 22 weeks of the treatment period.	Subjects were randomised to either of the 2 placebo arms (i.e., semaglutide placebo 0.5 mg and semaglutide placebo 1.0 mg) and then pooled for data analysis. Placebo 0.5 mg arm: Subjects were given 0.25 mg placebo once weekly s.c. injections for 4 weeks followed by 0.5 mg placebo once weekly s.c. injections for the remaining 26 weeks of the treatment period. Placebo 1.0 mg arm: Subjects were given 0.25 mg placebo once weekly s.c. injections for 4 weeks, 0.5 mg placebo once weekly s.c. injections for the next 4 weeks followed by 1.0 mg placebo once weekly s.c. injections for the remaining 22 weeks of the treatment period.
Measure Participants	128	130	129
Yes	74.2	72.3	24.8
No	25.8	27.7	75.2

6. Secondary Outcome

Title	Subjects Who Achieve (Yes/no):HbA1c Below or Equal to 6.5% (48 mmol/Mol) American Association of Clinical Endocrinologists Target
Description	Percentage of subjects who achieve (yes/no): HbA1c below 6.5% (48 mmol/mol) American Diabetes Association target after 30 weeks' treatment. Missing HbA1c data imputed from a mixed model for repeated measurements with treatment and country as fixed factors and baseline value as covariate, all nested within visit.
Time Frame	At 30 weeks of treatment

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	Semaglutide 0.5 mg	Semaglutide 1.0 mg	Placebo
Arm/Group Description	Subjects were given 0.25 mg semaglutide once weekly s.c. injection for 4 weeks followed by 0.5 mg semaglutide once weekly s.c. injections for the remaining 26 weeks of the treatment period.	Subjects were given 0.25 mg semaglutide once weekly s.c. injection for 4 weeks, 0.5 mg semaglutide once weekly s.c. injections for the next 4 weeks followed by 1.0 mg semaglutide once weekly s.c. injections for the remaining 22 weeks of the treatment period.	Subjects were randomised to either of the 2 placebo arms (i.e., semaglutide placebo 0.5 mg and semaglutide placebo 1.0 mg) and then pooled for data analysis. Placebo 0.5 mg arm: Subjects were given 0.25 mg placebo once weekly s.c. injections for 4 weeks followed by 0.5 mg placebo once weekly s.c. injections for the remaining 26 weeks of the treatment period. Placebo 1.0 mg arm: Subjects were given 0.25 mg placebo once weekly s.c. injections for 4 weeks, 0.5 mg placebo once weekly s.c. injections for the next 4 weeks followed by 1.0 mg placebo once weekly s.c. injections for the remaining 22 weeks of the treatment period.
Measure Participants	128	130	129
Yes	59.4	60.0	13.2
No	40.6	40.0	86.8

Adverse Events

Time Frame	From the first trial product administration (in week 0) till the date of the end-of-treatment follow-up visit (in week 35 + the 7-day visit window) or on the date of the last trial product administration plus 42 days (5 weeks plus the 7 days visit window)
Adverse Event Reporting Description	Safety analysis set (SAS) included all randomised subjects who had received at least 1 dose of randomised semaglutide or placebo.
Arm/Group Title	Semaglutide 0.5 mg		Semaglutide 1.0 mg		Placebo
Arm/Group Description	Subjects were given 0.25 mg semaglutide once weekly s.c. injection for 4 weeks followed by 0.5 mg semaglutide once weekly s.c. injections for the remaining 26 weeks of the treatment period.		Subjects were given 0.25 mg semaglutide once weekly s.c. injection for 4 weeks, 0.5 mg semaglutide once weekly s.c. injections for the next 4 weeks followed by 1.0 mg semaglutide once weekly s.c. injections for the remaining 22 weeks of the treatment period.		Subjects were randomised to either of the 2 placebo arms (i.e., semaglutide placebo 0.5 mg and semaglutide placebo 1.0 mg) and then pooled for data analysis. Placebo 0.5 mg arm: Subjects were given 0.25 mg placebo once weekly s.c. injections for 4 weeks followed by 0.5 mg placebo once weekly s.c. injections for the remaining 26 weeks of the treatment period. Placebo 1.0 mg arm: Subjects were given 0.25 mg placebo once weekly s.c. injections for 4 weeks, 0.5 mg placebo once weekly s.c. injections for the next 4 weeks followed by 1.0 mg placebo once weekly s.c. injections for the remaining 22 weeks of the treatment period.
All Cause Mortality
	Semaglutide 0.5 mg		Semaglutide 1.0 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Semaglutide 0.5 mg		Semaglutide 1.0 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/128 (5.5%)		7/130 (5.4%)		5/129 (3.9%)
Blood and lymphatic system disorders
Anaemia	0/128 (0%)	0	0/130 (0%)	0	1/129 (0.8%)	1
Cardiac disorders
Acute myocardial infarction	0/128 (0%)	0	1/130 (0.8%)	1	0/129 (0%)	0
Pericarditis	0/128 (0%)	0	1/130 (0.8%)	1	0/129 (0%)	0
Gastrointestinal disorders
Gastric haemorrhage	0/128 (0%)	0	0/130 (0%)	0	1/129 (0.8%)	2
Gastritis	1/128 (0.8%)	1	0/130 (0%)	0	0/129 (0%)	0
Oesophagitis	1/128 (0.8%)	1	0/130 (0%)	0	0/129 (0%)	0
General disorders
Inflammation	0/128 (0%)	0	0/130 (0%)	0	1/129 (0.8%)	1
Hepatobiliary disorders
Cholelithiasis	1/128 (0.8%)	1	0/130 (0%)	0	0/129 (0%)	0
Infections and infestations
Cystitis	1/128 (0.8%)	1	0/130 (0%)	0	0/129 (0%)	0
Encephalitis	1/128 (0.8%)	1	0/130 (0%)	0	0/129 (0%)	0
Lobar pneumonia	1/128 (0.8%)	1	0/130 (0%)	0	0/129 (0%)	0
Subcutaneous abscess	0/128 (0%)	0	0/130 (0%)	0	1/129 (0.8%)	1
Injury, poisoning and procedural complications
Wound	0/128 (0%)	0	1/130 (0.8%)	1	0/129 (0%)	0
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain	0/128 (0%)	0	0/130 (0%)	0	1/129 (0.8%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	1/128 (0.8%)	1	0/130 (0%)	0	0/129 (0%)	0
Prostate cancer	0/128 (0%)	0	1/130 (0.8%)	1	0/129 (0%)	0
Nervous system disorders
Transient ischaemic attack	1/128 (0.8%)	1	0/130 (0%)	0	0/129 (0%)	0
Psychiatric disorders
Mental disorder	1/128 (0.8%)	1	0/130 (0%)	0	0/129 (0%)	0
Renal and urinary disorders
Calculus ureteric	0/128 (0%)	0	1/130 (0.8%)	1	0/129 (0%)	0
Reproductive system and breast disorders
Postmenopausal haemorrhage	1/128 (0.8%)	1	0/130 (0%)	0	0/129 (0%)	0
Surgical and medical procedures
Coronary revascularisation	0/128 (0%)	0	1/130 (0.8%)	1	0/129 (0%)	0
Gastric bypass	0/128 (0%)	0	2/130 (1.5%)	2	0/129 (0%)	0
Other (Not Including Serious) Adverse Events
	Semaglutide 0.5 mg		Semaglutide 1.0 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	53/128 (41.4%)		47/130 (36.2%)		27/129 (20.9%)
Gastrointestinal disorders
Constipation	8/128 (6.3%)	9	5/130 (3.8%)	5	1/129 (0.8%)	2
Diarrhoea	16/128 (12.5%)	27	14/130 (10.8%)	19	3/129 (2.3%)	3
Dyspepsia	7/128 (5.5%)	13	5/130 (3.8%)	5	3/129 (2.3%)	3
Nausea	26/128 (20.3%)	44	31/130 (23.8%)	46	10/129 (7.8%)	12
Vomiting	5/128 (3.9%)	11	9/130 (6.9%)	15	2/129 (1.6%)	2
Infections and infestations
Nasopharyngitis	6/128 (4.7%)	7	6/130 (4.6%)	9	7/129 (5.4%)	9
Investigations
Lipase increased	8/128 (6.3%)	10	5/130 (3.8%)	5	5/129 (3.9%)	5
Nervous system disorders
Headache	15/128 (11.7%)	43	9/130 (6.9%)	18	8/129 (6.2%)	13

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