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

Diabetes Mellitus, Type 2 Clinical Trial

— SUSTAIN™1  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02054897
• Other study ID #: NN9535-3623
• Secondary ID: 2013-000632-94U1
• Status: Completed
• Phase: Phase 3
• Start date: February 3, 2014
• Est. completion date: May 8, 2015

Study information

• Verified date: May 2019
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 388
• Est. completion date: May 8, 2015
• Est. primary completion date: May 8, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• semaglutide
Once weekly, administrated subcutaneously (s.c. under the skin)
• placebo
Once weekly, administrated subcutaneously (s.c. under the skin)

Locations

Country	Name	City	State
Canada	Novo Nordisk Investigational Site	London	Ontario
Canada	Novo Nordisk Investigational Site	Montreal	Quebec
Canada	Novo Nordisk Investigational Site	Pointe-Claire	Quebec
Canada	Novo Nordisk Investigational Site	Toronto	Ontario
Canada	Novo Nordisk Investigational Site	Trois Rivières	Quebec
Canada	Novo Nordisk Investigational Site	Vancouver	British Columbia
Canada	Novo Nordisk Investigational Site	Winnipeg	Manitoba
Italy	Novo Nordisk Investigational Site	Catania
Italy	Novo Nordisk Investigational Site	Pisa
Italy	Novo Nordisk Investigational Site	Roma
Italy	Novo Nordisk Investigational Site	Rome
Italy	Novo Nordisk Investigational Site	Siena
Italy	Novo Nordisk Investigational Site	Terni
Japan	Novo Nordisk Investigational Site	Kyoto-shi, Kyoto
Japan	Novo Nordisk Investigational Site	Suita-shi, Osaka
Japan	Novo Nordisk Investigational Site	Tokyo
Japan	Novo Nordisk Investigational Site	Tokyo
Japan	Novo Nordisk Investigational Site	Tokyo
Mexico	Novo Nordisk Investigational Site	Aguascalientes
Mexico	Novo Nordisk Investigational Site	Ciudad Madero	Tamaulipas
Mexico	Novo Nordisk Investigational Site	Monterrey	Nuevo León
Romania	Novo Nordisk Investigational Site	Bucharest
Romania	Novo Nordisk Investigational Site	Bucharest
Romania	Novo Nordisk Investigational Site	Buzau
Romania	Novo Nordisk Investigational Site	Galati
Romania	Novo Nordisk Investigational Site	Oradea	Bihor
Russian Federation	Novo Nordisk Investigational Site	Arkhangelsk
Russian Federation	Novo Nordisk Investigational Site	Arkhangelsk
Russian Federation	Novo Nordisk Investigational Site	Chelyabinsk
Russian Federation	Novo Nordisk Investigational Site	Kazan
Russian Federation	Novo Nordisk Investigational Site	Novosibirsk
Russian Federation	Novo Nordisk Investigational Site	Saint-Petersburg
Russian Federation	Novo Nordisk Investigational Site	Saint-Petesburg
Russian Federation	Novo Nordisk Investigational Site	Saratov
Russian Federation	Novo Nordisk Investigational Site	Stavropol
South Africa	Novo Nordisk Investigational Site	Bloemfontein	Free State
South Africa	Novo Nordisk Investigational Site	Durban	KwaZulu-Natal
South Africa	Novo Nordisk Investigational Site	Johannesburg	Gauteng
South Africa	Novo Nordisk Investigational Site	Johannesburg	Gauteng
South Africa	Novo Nordisk Investigational Site	Krugersdorp	Gauteng
South Africa	Novo Nordisk Investigational Site	Port Elizabeth	Eastern Cape
South Africa	Novo Nordisk Investigational Site	Pretoria	Gauteng
South Africa	Novo Nordisk Investigational Site	Sophiatown	Gauteng
South Africa	Novo Nordisk Investigational Site	Umkomaas	KwaZulu-Natal
United Kingdom	Novo Nordisk Investigational Site	Cardiff
United Kingdom	Novo Nordisk Investigational Site	Dundee
United Kingdom	Novo Nordisk Investigational Site	St Helens
United Kingdom	Novo Nordisk Investigational Site	Swansea
United States	Novo Nordisk Investigational Site	Albuquerque	New Mexico
United States	Novo Nordisk Investigational Site	Anniston	Alabama
United States	Novo Nordisk Investigational Site	Belvidere	New Jersey
United States	Novo Nordisk Investigational Site	Billings	Montana
United States	Novo Nordisk Investigational Site	Birmingham	Alabama
United States	Novo Nordisk Investigational Site	Boynton Beach	Florida
United States	Novo Nordisk Investigational Site	Brownsburg	Indiana
United States	Novo Nordisk Investigational Site	Charlotte	North Carolina
United States	Novo Nordisk Investigational Site	Cincinnati	Ohio
United States	Novo Nordisk Investigational Site	Colorado Springs	Colorado
United States	Novo Nordisk Investigational Site	Dallas	Texas
United States	Novo Nordisk Investigational Site	Delaware	Ohio
United States	Novo Nordisk Investigational Site	Franklin	Indiana
United States	Novo Nordisk Investigational Site	Hawaiian Gardens	California
United States	Novo Nordisk Investigational Site	Jacksonville	Florida
United States	Novo Nordisk Investigational Site	Levittown	Pennsylvania
United States	Novo Nordisk Investigational Site	Lexington	Kentucky
United States	Novo Nordisk Investigational Site	Lomita	California
United States	Novo Nordisk Investigational Site	Los Angeles	California
United States	Novo Nordisk Investigational Site	Miami	Florida
United States	Novo Nordisk Investigational Site	Miami	Florida
United States	Novo Nordisk Investigational Site	Miami	Florida
United States	Novo Nordisk Investigational Site	Miami	Florida
United States	Novo Nordisk Investigational Site	Miami	Florida
United States	Novo Nordisk Investigational Site	Miami Lakes	Florida
United States	Novo Nordisk Investigational Site	Montclair	California
United States	Novo Nordisk Investigational Site	Northridge	California
United States	Novo Nordisk Investigational Site	Olive Branch	Mississippi
United States	Novo Nordisk Investigational Site	Omaha	Nebraska
United States	Novo Nordisk Investigational Site	Pell City	Alabama
United States	Novo Nordisk Investigational Site	Pembroke Pines	Florida
United States	Novo Nordisk Investigational Site	Savannah	Georgia
United States	Novo Nordisk Investigational Site	Sealy	Texas
United States	Novo Nordisk Investigational Site	Spartanburg	South Carolina
United States	Novo Nordisk Investigational Site	Sugar Land	Texas
United States	Novo Nordisk Investigational Site	Sugar Land	Texas
United States	Novo Nordisk Investigational Site	Whiteville	North Carolina
United States	Novo Nordisk Investigational Site	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Canada,  Italy,  Japan,  Mexico,  Romania,  Russian Federation,  South Africa,  United Kingdom, 

References & Publications (10)

Ahrén B, Atkin SL, Charpentier G, Warren ML, Wilding JPH, Birch S, Holst AG, Leiter LA. Semaglutide induces weight loss in subjects with type 2 diabetes regardless of baseline BMI or gastrointestinal adverse events in the SUSTAIN 1 to 5 trials. Diabetes O — View Citation

Aroda VR, Ahmann A, Cariou B, Chow F, Davies MJ, Jódar E, Mehta R, Woo V, Lingvay I. Comparative efficacy, safety, and cardiovascular outcomes with once-weekly subcutaneous semaglutide in the treatment of type 2 diabetes: Insights from the SUSTAIN 1-7 tri — View Citation

Carlsson Petri KC, Ingwersen SH, Flint A, Zacho J, Overgaard RV. Semaglutide s.c. Once-Weekly in Type 2 Diabetes: A Population Pharmacokinetic Analysis. Diabetes Ther. 2018 Aug;9(4):1533-1547. doi: 10.1007/s13300-018-0458-5. Epub 2018 Jun 15. — View Citation

DeVries JH, Desouza C, Bellary S, Unger J, Hansen OKH, Zacho J, Woo V. Achieving glycaemic control without weight gain, hypoglycaemia, or gastrointestinal adverse events in type 2 diabetes in the SUSTAIN clinical trial programme. Diabetes Obes Metab. 2018 — View Citation

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] — View Citation

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. — View Citation

Petri KCC, Ingwersen SH, Flint A, Zacho J, Overgaard RV. Exposure-response analysis for evaluation of semaglutide dose levels in type 2 diabetes. Diabetes Obes Metab. 2018 Sep;20(9):2238-2245. doi: 10.1111/dom.13358. Epub 2018 Jun 15. — View Citation

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 VS COMPARATORS IN TYPE 2 DIABETES. Endocr Pract. 2019 Mar 13. doi: 10.4158/EP-2018-0444. [Epub ahead of print] — View Citation

Sorli C, Harashima SI, Tsoukas GM, Unger J, Karsbøl JD, Hansen T, Bain SC. Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes (SUSTAIN 1): a double-blind, randomised, placebo-controlled, parallel-gro — View Citation

Warren M, Chaykin L, Trachtenbarg D, Nayak G, Wijayasinghe N, Cariou B. Semaglutide as a therapeutic option for elderly patients with type 2 diabetes: Pooled analysis of the SUSTAIN 1-5 trials. Diabetes Obes Metab. 2018 Sep;20(9):2291-2297. doi: 10.1111/d — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in HbA1c (Glycosylated Haemoglobin)	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.	Week 0, week 30
Secondary	Change in Body Weight	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.	Week 0, week 30
Secondary	Change in Fasting Plasma Glucose (FPG)	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.	Week 0, week 30
Secondary	Change in Systolic and Diastolic Blood Pressure	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.	Week 0, week 30
Secondary	Subjects Who Achieve (Yes/no):HbA1c Below 7.0% (53 mmol/Mol) American Diabetes Association Target	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.	At 30 weeks of treatment
Secondary	Subjects Who Achieve (Yes/no):HbA1c Below or Equal to 6.5% (48 mmol/Mol) American Association of Clinical Endocrinologists Target	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.	At 30 weeks of treatment

External Links

•   Clinical Trials at Novo Nordisk