Clinical trial NCT02305381: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes
Diabetes Mellitus, Type 2
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2014-12-02
Enrollment: 397
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in HbA1c (Glycosylated Haemoglobin)
timeFrame: Week 0, week 30
Secondary outcomes:
measure: Change in Body Weight
timeFrame: Week 0, week 30
measure: Change in Fasting Plasma Glucose (FPG)
timeFrame: week 0, week 30
measure: Change in Insulin Dose
timeFrame: week 0, week 30
measure: Change in Systolic and Diastolic Blood Pressure
timeFrame: week 0, week 30
measure: Patient Reported Outcomes, Diabetes Treatment Satisfaction Questionnaire (DTSQ)
timeFrame: week 0, week 30
measure: HbA1c Below 7.0% (53 mmol/Mol) American Diabetes Association (ADA) Target
timeFrame: After 30 weeks treatment
measure: HbA1c Below or Equal to 6.5% (48 mmol/Mol) American Association of Clinical Endocrinologists (AACE) Target
timeFrame: After 30 weeks treatment
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Novo Nordisk Investigational Site
state: Arizona
city: Anaheim
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Fresno
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Lomita
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Los Angeles
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Northridge
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Poway
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Riverside
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Roseville
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: San Ramon
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Van Nuys
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Walnut Creek
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Waterbury
country: United States
facility: Novo Nordisk Investigational Site
state: Connecticut
city: Bradenton
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Fleming Island
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Jacksonville
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Port Charlotte
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Spring Hill
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Tampa
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Roswell
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Chicago
country: United States
facility: Novo Nordisk Investigational Site
state: Illinois
city: Chicago
country: United States
facility: Novo Nordisk Investigational Site
state: Illinois
city: Gillespie
country: United States
facility: Novo Nordisk Investigational Site
state: Illinois
city: Skokie
country: United States
facility: Novo Nordisk Investigational Site
state: Illinois
city: Avon
country: United States
facility: Novo Nordisk Investigational Site
state: Indiana
city: Greenfield
country: United States
facility: Novo Nordisk Investigational Site
state: Indiana
city: Indianapolis
country: United States
facility: Novo Nordisk Investigational Site
state: Indiana
city: Muncie
country: United States
facility: Novo Nordisk Investigational Site
state: Indiana
city: Council Bluffs
country: United States
facility: Novo Nordisk Investigational Site
state: Iowa
city: Overland Park
country: United States
facility: Novo Nordisk Investigational Site
state: Kansas
city: Topeka
country: United States
facility: Novo Nordisk Investigational Site
state: Kansas
city: Lexington
country: United States
facility: Novo Nordisk Investigational Site
state: Kentucky
city: Paducah
country: United States
facility: Novo Nordisk Investigational Site
state: Kentucky
city: Metairie
country: United States
facility: Novo Nordisk Investigational Site
state: Louisiana
city: Rockville
country: United States
facility: Novo Nordisk Investigational Site
state: Maryland
city: Waltham
country: United States
facility: Novo Nordisk Investigational Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: Novo Nordisk Investigational Site
state: Michigan
city: Flint
country: United States
facility: Novo Nordisk Investigational Site
state: Michigan
city: Kalamazoo
country: United States
facility: Novo Nordisk Investigational Site
state: Michigan
city: Jackson
country: United States
facility: Novo Nordisk Investigational Site
state: Mississippi
city: Las Vegas
country: United States
facility: Novo Nordisk Investigational Site
state: Nevada
city: Las Vegas
country: United States
facility: Novo Nordisk Investigational Site
state: Nevada
city: Teaneck
country: United States
facility: Novo Nordisk Investigational Site
state: New Jersey
city: Albuquerque
country: United States
facility: Novo Nordisk Investigational Site
state: New Mexico
city: West Seneca
country: United States
facility: Novo Nordisk Investigational Site
state: New York
city: Cincinnati
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Cincinnati
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Cincinnati
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Dayton
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Kettering
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Oklahoma City
country: United States
facility: Novo Nordisk Investigational Site
state: Oklahoma
city: Yukon
country: United States
facility: Novo Nordisk Investigational Site
state: Oklahoma
city: Levittown
country: United States
facility: Novo Nordisk Investigational Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Novo Nordisk Investigational Site
state: Pennsylvania
city: Athens
country: United States
facility: Novo Nordisk Investigational Site
state: Tennessee
city: Bristol
country: United States
facility: Novo Nordisk Investigational Site
state: Tennessee
city: Chattanooga
country: United States
facility: Novo Nordisk Investigational Site
state: Tennessee
city: Kingsport
country: United States
facility: Novo Nordisk Investigational Site
state: Tennessee
city: Amarillo
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Dallas
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Dallas
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Fort Worth
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Houston
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Hurst
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Katy
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Mesquite
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: San Antonio
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Sugar Land
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Sugar Land
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Bountiful
country: United States
facility: Novo Nordisk Investigational Site
state: Utah
city: Richmond
country: United States
facility: Novo Nordisk Investigational Site
state: Virginia
city: Kenosha
country: United States
facility: Novo Nordisk Investigational Site
state: Wisconsin
city: Essen
country: Germany
facility: Novo Nordisk Investigational Site
city: Falkensee
country: Germany
facility: Novo Nordisk Investigational Site
city: Friedrichsthal
country: Germany
facility: Novo Nordisk Investigational Site
city: Hamburg
country: Germany
facility: Novo Nordisk Investigational Site
city: Hamburg
country: Germany
facility: Novo Nordisk Investigational Site
city: Hamburg
country: Germany
facility: Novo Nordisk Investigational Site
city: Hohenmölsen
country: Germany
facility: Novo Nordisk Investigational Site
city: Münster
country: Germany
facility: Novo Nordisk Investigational Site
city: Rehlingen-Siersburg
country: Germany
facility: Novo Nordisk Investigational Site
city: Saint Ingbert-Oberwürzbach
country: Germany
facility: Novo Nordisk Investigational Site
city: Stuttgart
country: Germany
facility: Novo Nordisk Investigational Site
city: Sulzbach-Rosenberg
country: Germany
facility: Novo Nordisk Investigational Site
city: Ibaraki
country: Japan
facility: Novo Nordisk Investigational Site
city: Kashiwara-shi, Osaka
country: Japan
facility: Novo Nordisk Investigational Site
city: Kumamoto-shi, Kumamoto
country: Japan
facility: Novo Nordisk Investigational Site
city: Miyazaki
country: Japan
facility: Novo Nordisk Investigational Site
city: Osaka
country: Japan
facility: Novo Nordisk Investigational Site
city: Tokyo
country: Japan
facility: Novo Nordisk Investigational Site
city: Manati
country: Puerto Rico
facility: Novo Nordisk Investigational Site
city: Belgrade
country: Serbia
facility: Novo Nordisk Investigational Site
city: Kragujevac
country: Serbia
facility: Novo Nordisk Investigational Site
city: Novi Sad
country: Serbia
facility: Novo Nordisk Investigational Site
city: Bratislava
country: Slovakia
facility: Novo Nordisk Investigational Site
city: Kosice
country: Slovakia
facility: Novo Nordisk Investigational Site
city: Levice
country: Slovakia
facility: Novo Nordisk Investigational Site
city: Lucenec
country: Slovakia
facility: Novo Nordisk Investigational Site
city: Presov
country: Slovakia
facility: Novo Nordisk Investigational Site
Study officials:
affiliation: Novo Nordisk A/S
name: Global Clinical Registry (GCR, 1452)
role: STUDY_DIRECTOR
References:
citation: Rodbard HW, Bellary S, Hramiak I, Seino Y, Silver R, Damgaard LH, Nayak G, Zacho J, Aroda VR. GREATER COMBINED REDUCTIONS IN HbA1C >/=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.
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 2 diabetes (SUSTAIN 5). Diabetologia. 2016; 59: S364-5.
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):2291-2301. doi: 10.1210/jc.2018-00070.
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/dom.13331. Epub 2018 Jun 7.
citation: Ahren 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 Obes Metab. 2018 Sep;20(9):2210-2219. doi: 10.1111/dom.13353. Epub 2018 Jun 12.
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 Oct;20(10):2426-2434. doi: 10.1111/dom.13396. Epub 2018 Jul 9.
citation: Aroda VR, Ahmann A, Cariou B, Chow F, Davies MJ, Jodar 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 trials. Diabetes Metab. 2019 Oct;45(5):409-418. doi: 10.1016/j.diabet.2018.12.001. Epub 2019 Jan 4.
citation: Husain M, Bain SC, Holst AG, Mark T, Rasmussen S, Lingvay I. Effects of semaglutide on risk of cardiovascular events across a continuum of cardiovascular risk: combined post hoc analysis of the SUSTAIN and PIONEER trials. Cardiovasc Diabetol. 2020 Sep 30;19(1):156. doi: 10.1186/s12933-020-01106-4.
citation: Husain M, Bain SC, Jeppesen OK, Lingvay I, Sorrig R, Treppendahl MB, Vilsboll T. Semaglutide (SUSTAIN and PIONEER) reduces cardiovascular events in type 2 diabetes across varying cardiovascular risk. Diabetes Obes Metab. 2020 Mar;22(3):442-451. doi: 10.1111/dom.13955. Epub 2020 Feb 5.
citation: DeSouza C, Cariou B, Garg S, Lausvig N, Navarria A, Fonseca V. Efficacy and Safety of Semaglutide for Type 2 Diabetes by Race and Ethnicity: A Post Hoc Analysis of the SUSTAIN Trials. J Clin Endocrinol Metab. 2020 Feb 1;105(2):dgz072. doi: 10.1210/clinem/dgz072.
citation: Jendle J, Birkenfeld AL, Polonsky WH, Silver R, Uusinarkaus K, Hansen T, Hakan-Bloch J, Tadayon S, Davies MJ. Improved treatment satisfaction in patients with type 2 diabetes treated with once-weekly semaglutide in the SUSTAIN trials. Diabetes Obes Metab. 2019 Oct;21(10):2315-2326. doi: 10.1111/dom.13816. Epub 2019 Jul 12.