Efficacy and Safety of Semaglutide Once-weekly Versus Placebo as add-on to Basal Insulin Alone or Basal Insulin in Combination With Metformin in Subjects With Type 2 Diabetes

Diabetes Mellitus, Type 2 Clinical Trial

— SUSTAIN™ 5  

Official title:

Efficacy and Safety of Semaglutide Once-weekly Versus Placebo as add-on to Basal Insulin Alone or Basal Insulin in Combination With Metformin in Subjects With Type 2 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02305381
• Other study ID #: NN9535-3627
• Secondary ID: 2013-004502-26U1
• Status: Completed
• Phase: Phase 3
• Start date: December 1, 2014
• Est. completion date: November 21, 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 in Asia, Europe and the United States of America (USA). The aim of the trial is to investigate efficacy and safety of semaglutide once weekly versus placebo as add-on to basal insulin alone or basal insulin in combination with metformin in subjects with type 2 diabetes.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 397
• Est. completion date: November 21, 2015
• Est. primary completion date: November 21, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria: - Male or female, age at least 18 years at the time of signing inform consent. For Japan: Male or female, age at least 20 years at the time of signing informed consent - Subjects diagnosed with T2DM (type 2 diabetes mellitus) and on stable diabetes treatment (plus/minus 20 percent change in total daily dose) with basal insulin (minimum of 0.25 IU/kg/day and/or 20 IU/day of: insulin glargine, insulin detemir, insulin degludec and/or NPH insulin) alone or in combination with metformin (minimum of 1500 mg/day or maximal tolerable dose) for 90 days prior to screening - HbA1c (glycosylated haemoglobin) 7.0 - 10.0 percent (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 an adequate contraceptive method throughout the trial including the 5 weeks follow-up period (adequate contraceptive measures as required by local regulation or practice). Germany: Only highly effective methods of birth control are accepted (ie one that results in less than 1% per year failure rate when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intrauterine device), or sexual abstinence or vasectomised partner. Japan: Adequate contraceptive measures are abstinence (not having sex), diaphragm, condom (by the partner), intrauterine device, sponge, spermicide or oral contraceptives - Treatment with any glucose lowering agents other than stated in the inclusion criteria in a period of 90 days before screening. An exception is short-term treatment (7 days or less in total) with bolus insulin in connection with intercurrent illness - Experienced more than 3 episodes of severe hypoglycaemia within 6 months prior to screening, and/or hypoglycaemia unawareness - History of pancreatitis (acute or chronic) - Screening calcitonin value above or equal to 50 ng/L (pg/mL) - Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome 2 (MEN 2) - Severe renal impairment 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 (NYHA) Class IV

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• semaglutide
Injected subcutaneously (s.c. under the skin) once-weekly. As add-on to the pre-trial background medication.
• placebo
Injected subcutaneously (s.c. under the skin) once-weekly. As add-on to the pre-trial background medication.

Locations

Country	Name	City	State
Germany	Novo Nordisk Investigational Site	Essen
Germany	Novo Nordisk Investigational Site	Falkensee
Germany	Novo Nordisk Investigational Site	Friedrichsthal
Germany	Novo Nordisk Investigational Site	Hamburg
Germany	Novo Nordisk Investigational Site	Hamburg
Germany	Novo Nordisk Investigational Site	Hamburg
Germany	Novo Nordisk Investigational Site	Hohenmölsen
Germany	Novo Nordisk Investigational Site	Münster
Germany	Novo Nordisk Investigational Site	Rehlingen-Siersburg
Germany	Novo Nordisk Investigational Site	Saint Ingbert-Oberwürzbach
Germany	Novo Nordisk Investigational Site	Stuttgart
Germany	Novo Nordisk Investigational Site	Sulzbach-Rosenberg
Japan	Novo Nordisk Investigational Site	Ibaraki
Japan	Novo Nordisk Investigational Site	Kashiwara-shi, Osaka
Japan	Novo Nordisk Investigational Site	Kumamoto-shi, Kumamoto
Japan	Novo Nordisk Investigational Site	Miyazaki
Japan	Novo Nordisk Investigational Site	Osaka
Japan	Novo Nordisk Investigational Site	Tokyo
Puerto Rico	Novo Nordisk Investigational Site	Manati
Serbia	Novo Nordisk Investigational Site	Belgrade
Serbia	Novo Nordisk Investigational Site	Kragujevac
Serbia	Novo Nordisk Investigational Site	Novi Sad
Slovakia	Novo Nordisk Investigational Site	Bratislava
Slovakia	Novo Nordisk Investigational Site	Kosice
Slovakia	Novo Nordisk Investigational Site	Levice
Slovakia	Novo Nordisk Investigational Site	Lucenec
Slovakia	Novo Nordisk Investigational Site	Presov
United States	Novo Nordisk Investigational Site	Albuquerque	New Mexico
United States	Novo Nordisk Investigational Site	Amarillo	Texas
United States	Novo Nordisk Investigational Site	Anaheim	California
United States	Novo Nordisk Investigational Site	Ann Arbor	Michigan
United States	Novo Nordisk Investigational Site	Athens	Tennessee
United States	Novo Nordisk Investigational Site	Avon	Indiana
United States	Novo Nordisk Investigational Site	Bountiful	Utah
United States	Novo Nordisk Investigational Site	Bradenton	Florida
United States	Novo Nordisk Investigational Site	Bristol	Tennessee
United States	Novo Nordisk Investigational Site	Chattanooga	Tennessee
United States	Novo Nordisk Investigational Site	Chicago	Illinois
United States	Novo Nordisk Investigational Site	Chicago	Illinois
United States	Novo Nordisk Investigational Site	Cincinnati	Ohio
United States	Novo Nordisk Investigational Site	Cincinnati	Ohio
United States	Novo Nordisk Investigational Site	Cincinnati	Ohio
United States	Novo Nordisk Investigational Site	Council Bluffs	Iowa
United States	Novo Nordisk Investigational Site	Dallas	Texas
United States	Novo Nordisk Investigational Site	Dallas	Texas
United States	Novo Nordisk Investigational Site	Dayton	Ohio
United States	Novo Nordisk Investigational Site	Fleming Island	Florida
United States	Novo Nordisk Investigational Site	Flint	Michigan
United States	Novo Nordisk Investigational Site	Fort Worth	Texas
United States	Novo Nordisk Investigational Site	Fresno	California
United States	Novo Nordisk Investigational Site	Gillespie	Illinois
United States	Novo Nordisk Investigational Site	Greenfield	Indiana
United States	Novo Nordisk Investigational Site	Houston	Texas
United States	Novo Nordisk Investigational Site	Hurst	Texas
United States	Novo Nordisk Investigational Site	Indianapolis	Indiana
United States	Novo Nordisk Investigational Site	Jackson	Mississippi
United States	Novo Nordisk Investigational Site	Jacksonville	Florida
United States	Novo Nordisk Investigational Site	Kalamazoo	Michigan
United States	Novo Nordisk Investigational Site	Katy	Texas
United States	Novo Nordisk Investigational Site	Kenosha	Wisconsin
United States	Novo Nordisk Investigational Site	Kettering	Ohio
United States	Novo Nordisk Investigational Site	Kingsport	Tennessee
United States	Novo Nordisk Investigational Site	Las Vegas	Nevada
United States	Novo Nordisk Investigational Site	Las Vegas	Nevada
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	Mesquite	Texas
United States	Novo Nordisk Investigational Site	Metairie	Louisiana
United States	Novo Nordisk Investigational Site	Muncie	Indiana
United States	Novo Nordisk Investigational Site	Northridge	California
United States	Novo Nordisk Investigational Site	Oklahoma City	Oklahoma
United States	Novo Nordisk Investigational Site	Overland Park	Kansas
United States	Novo Nordisk Investigational Site	Paducah	Kentucky
United States	Novo Nordisk Investigational Site	Philadelphia	Pennsylvania
United States	Novo Nordisk Investigational Site	Phoenix	Arizona
United States	Novo Nordisk Investigational Site	Port Charlotte	Florida
United States	Novo Nordisk Investigational Site	Poway	California
United States	Novo Nordisk Investigational Site	Richmond	Virginia
United States	Novo Nordisk Investigational Site	Riverside	California
United States	Novo Nordisk Investigational Site	Rockville	Maryland
United States	Novo Nordisk Investigational Site	Roseville	California
United States	Novo Nordisk Investigational Site	Roswell	Georgia
United States	Novo Nordisk Investigational Site	San Antonio	Texas
United States	Novo Nordisk Investigational Site	San Ramon	California
United States	Novo Nordisk Investigational Site	Skokie	Illinois
United States	Novo Nordisk Investigational Site	Spring Hill	Florida
United States	Novo Nordisk Investigational Site	Sugar Land	Texas
United States	Novo Nordisk Investigational Site	Sugar Land	Texas
United States	Novo Nordisk Investigational Site	Tampa	Florida
United States	Novo Nordisk Investigational Site	Teaneck	New Jersey
United States	Novo Nordisk Investigational Site	Topeka	Kansas
United States	Novo Nordisk Investigational Site	Van Nuys	California
United States	Novo Nordisk Investigational Site	Walnut Creek	California
United States	Novo Nordisk Investigational Site	Waltham	Massachusetts
United States	Novo Nordisk Investigational Site	Waterbury	Connecticut
United States	Novo Nordisk Investigational Site	West Seneca	New York
United States	Novo Nordisk Investigational Site	Yukon	Oklahoma

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Germany,  Japan,  Puerto Rico,  Serbia,  Slovakia, 

References & Publications (7)

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

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

Rodbard H, Lingvay I, Reed J, de la Rosa R, Rose L, Sugimoto D, Araki E, Chu P-L, Wijayasinghe N, Norwood P. Efficacy and safety of semaglutide once-weekly vs placebo as add-on to basal insulin alone or in combination with metformin in subjects with type

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

Rodbard HW, Lingvay I, Reed J, de la Rosa R, Rose L, Sugimoto D, Araki E, Chu PL, Wijayasinghe N, Norwood P. Semaglutide Added to Basal Insulin in Type 2 Diabetes (SUSTAIN 5): A Randomized, Controlled Trial. J Clin Endocrinol Metab. 2018 Jun 1;103(6):2291 — 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)	Estimated mean change from baseline in HbA1c at week 30. The post-baseline responses are analysed using a mixed model for repeated measurements with treatment, country and stratification variable (HbA1c level at screening [<= 8.0% or > 8.0%] crossed with use of metformin [yes or no]; 2 by 2 levels) as fixed factors and baseline value as covariate, all nested within visit. Mean estimates are adjusted according to observed baseline distribution. Missing data was imputed using mixed model for repeated measurements.	Week 0, week 30
Secondary	Change in Body Weight	Estimated mean change from baseline in body weight at week 30. The post-baseline responses are analysed using a mixed model for repeated measurements with treatment, country and stratification variable (HbA1c level at screening [<= 8.0% or > 8.0%] crossed with use of metformin [yes or no]; 2 by 2 levels) as fixed factors and baseline value as covariate, all nested within visit. Mean estimates are adjusted according to observed baseline distribution. Missing data was imputed using mixed model for repeated measurements.	Week 0, week 30
Secondary	Change in Fasting Plasma Glucose (FPG)	Estimated mean change from baseline in FPG at week 30. The post-baseline responses are analysed using a mixed model for repeated measurements with treatment, country and stratification variable (HbA1c level at screening [<= 8.0% or > 8.0%] crossed with use of metformin [yes or no]; 2 by 2 levels) as fixed factors and baseline value as covariate, all nested within visit. Mean estimates are adjusted according to observed baseline distribution. Missing data was imputed using mixed model for repeated measurements.	week 0, week 30
Secondary	Change in Insulin Dose	Estimated mean change from baseline in insulin dose at week 30 was measured in terms of ratio to baseline. Responses at week 30 are analysed using an Analysis of covariance model with treatment, country and stratification variable (HbA1c level at screening [<= 8.0% or > 8.0%] crossed with use of metformin [yes or no]; 2 by 2 levels) as fixed factors and baseline value as covariate. Mean estimates are adjusted according to observed baseline distribution. Missing data was imputed using last observation carried forward.	week 0, week 30
Secondary	Change in Systolic and Diastolic Blood Pressure	Estimated mean change from baseline in systolic and diastolic blood pressure at week 30. The post-baseline responses are analysed using a mixed model for repeated measurements with treatment, country and stratification variable (HbA1c level at screening [<= 8.0% or > 8.0%] crossed with use of metformin [yes or no]; 2 by 2 levels) as fixed factors and baseline value as covariate, all nested within visit. Mean estimates are adjusted according to observed baseline distribution. Missing data was imputed using mixed model for repeated measurements.	week 0, week 30
Secondary	Patient Reported Outcomes, Diabetes Treatment Satisfaction Questionnaire (DTSQ)	The DTSQs questionnaire was used to assess subjects' treatment satisfaction and contained 8 components and evaluates the diabetes treatment (including insulin, tablets and/or diet) in terms of convenience, flexibility and general feelings towards the treatment. The result presented is the 'Treatment Satisfaction' summary score, which is the sum of 6 of the 8 items of the DTSQs questionnaire. Response options range from 6 (best case) to 0 (worst case). Total scores for treatment satisfaction range from 0-36. Higher scores indicate higher satisfaction. The post-baseline responses are analysed using an ANCOVA model with treatment, country and stratification variables (HbA1c level at screening [<= 8.0% or > 8.0%] and use of metformin [yes or no]) as fixed factors and baseline value as covariate. Mean estimates are adjusted according to observed baseline distribution. Missing data was imputed using last observation carried forward.	week 0, week 30
Secondary	HbA1c Below 7.0% (53 mmol/Mol) American Diabetes Association (ADA) Target	Percentage of subjects with HbA1C below 7.0% after 30 weeks treatment. Missing data imputed from a mixed model for repeated measurements with treatment, country and stratification variable (HbA1c level at screening [<= 8.0% or > 8.0%] crossed with use of metformin [yes or no]; 2 by 2 levels) as fixed factors and baseline value as covariate, all nested within visit.	After 30 weeks treatment
Secondary	HbA1c Below or Equal to 6.5% (48 mmol/Mol) American Association of Clinical Endocrinologists (AACE) Target	Percentage of participants with HbA1c below or equal to 6.5% after 30 weeks treatment. Missing data imputed from a mixed model for repeated measurements with treatment, country and stratification variable (HbA1c level at screening [<= 8.0% or > 8.0%] crossed with use of metformin [yes or no]; 2 by 2 levels) as fixed factors and baseline value as covariate, all nested within visit.	After 30 weeks treatment

External Links

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