Clinical trial NCT01885208: Efficacy and Safety of Semaglutide Once-weekly Versus Exenatide ER 2.0 mg Once-weekly as add-on to 1-2 Oral Antidiabetic Drugs (OADs) in Subjects With Type 2 Diabetes
Official title: Efficacy and Safety of Semaglutide Once-weekly Versus Exenatide ER 2.0 mg Once-weekly as add-on to 1-2 Oral Antidiabetic Drugs (OADs) in Subjects With Type 2 Diabetes (SUSTAIN™ 3 - vs. QW GLP-1)
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: 2013-06-24
Enrollment: 813
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 Europe and North and South America. The aim of the trial is to investigate the efficacy and safety of semaglutide once-weekly versus exenatide ER (extended release) 2.0 mg once-weekly as add-on to 1-2 oral antidiabetic drugs (OADs) in subjects with type 2 diabetes.


Eligibility criteria: Inclusion Criteria: - Subjects diagnosed with type 2 diabetes and on stable diabetes treatment with 1-2 OADs (Metformin equal to or above 1500 mg or maximum tolerated dose and/or thiazolidinedione (TZD) and sulfonylureas (SUs) equal to or above half of maximum dose allowed according to national label) for at least 90 days prior to screening. Stable is defined as unchanged medication and unchanged dose - HbA1c 7.0 - 10.5 % (53 - 91 mmol/mol) (both inclusive) Exclusion Criteria: - Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using an adequate contraceptive method throughout the trial including the 5 week follow-up period (adequate contraceptive measures as required by local law or practice) - 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 glucose lowering agent(s) 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 insulin in connection with inter-current illness - History of chronic or idiopathic acute pancreatitis - Screening calcitonin value equal to or above 50 ng/L (pg/mL) - Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN 2) - Impaired renal function defined as estimated glomerular filtration rate (eGFR) below 60 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 From Baseline in HbA1c (Glycosylated Haemoglobin)
timeFrame: Week 0, week 56
Secondary outcomes:
measure: Change From Baseline in Body Weight
timeFrame: Week 0, week 56
measure: Change From Baseline in Fasting Plasma Glucose (FPG)
timeFrame: Week 0, week 56
measure: Change From Baseline in Systolic and Diastolic Blood Pressure
timeFrame: Week 0, week 56
measure: Change From Baseline in Patient Reported Outcome (PRO) Questionnaire Diabetes Treatment Satisfaction Questionnaire Status (DTSQs)
timeFrame: Week 0, week 56
measure: Subjects Who Achieve HbA1c Equal to or Below 6.5% (48 mmol/Mol) American Association of Clinical Endocrinologists (AACE) Target: (Yes/no)
timeFrame: After 56 weeks' treatment
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Novo Nordisk Investigational Site
state: Alabama
city: Birmingham
country: United States
facility: Novo Nordisk Investigational Site
state: Alabama
city: Pell City
country: United States
facility: Novo Nordisk Investigational Site
state: Alabama
city: Glendale
country: United States
facility: Novo Nordisk Investigational Site
state: Arizona
city: Mesa
country: United States
facility: Novo Nordisk Investigational Site
state: Arizona
city: Phoenix
country: United States
facility: Novo Nordisk Investigational Site
state: Arizona
city: Burbank
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Hawaiian Gardens
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: Los Angeles
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: Northridge
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: San Diego
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Tustin
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Colorado Springs
country: United States
facility: Novo Nordisk Investigational Site
state: Colorado
city: Colorado Springs
country: United States
facility: Novo Nordisk Investigational Site
state: Colorado
city: Bradenton
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Brandon
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Coral Gables
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Hialeah
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Jacksonville
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Miami Lakes
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Miami
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Miami
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Miami
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Plantation
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Savannah
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Chicago
country: United States
facility: Novo Nordisk Investigational Site
state: Illinois
city: Franklin
country: United States
facility: Novo Nordisk Investigational Site
state: Indiana
city: Greenfield
country: United States
facility: Novo Nordisk Investigational Site
state: Indiana
city: Muncie
country: United States
facility: Novo Nordisk Investigational Site
state: Indiana
city: Louisville
country: United States
facility: Novo Nordisk Investigational Site
state: Kentucky
city: Madisonville
country: United States
facility: Novo Nordisk Investigational Site
state: Kentucky
city: Hyattsville
country: United States
facility: Novo Nordisk Investigational Site
state: Maryland
city: Kalamazoo
country: United States
facility: Novo Nordisk Investigational Site
state: Michigan
city: Saint Louis
country: United States
facility: Novo Nordisk Investigational Site
state: Missouri
city: Las Vegas
country: United States
facility: Novo Nordisk Investigational Site
state: Nevada
city: Mine Hill
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: North Massapequa
country: United States
facility: Novo Nordisk Investigational Site
state: New York
city: Syracuse
country: United States
facility: Novo Nordisk Investigational Site
state: New York
city: West Seneca
country: United States
facility: Novo Nordisk Investigational Site
state: New York
city: Greensboro
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Hickory
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Whiteville
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Akron
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Cincinnati
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Cleveland
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Delaware
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Corvallis
country: United States
facility: Novo Nordisk Investigational Site
state: Oregon
city: Portland
country: United States
facility: Novo Nordisk Investigational Site
state: Oregon
city: Portland
country: United States
facility: Novo Nordisk Investigational Site
state: Oregon
city: Lansdale
country: United States
facility: Novo Nordisk Investigational Site
state: Pennsylvania
city: Norristown
country: United States
facility: Novo Nordisk Investigational Site
state: Pennsylvania
city: Charleston
country: United States
facility: Novo Nordisk Investigational Site
state: South Carolina
city: Mount Pleasant
country: United States
facility: Novo Nordisk Investigational Site
state: South Carolina
city: Murrells Inlet
country: United States
facility: Novo Nordisk Investigational Site
state: South Carolina
city: Spartanburg
country: United States
facility: Novo Nordisk Investigational Site
state: South Carolina
city: Chattanooga
country: United States
facility: Novo Nordisk Investigational Site
state: Tennessee
city: Austin
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Carrollton
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: Houston
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Houston
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Houston
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Irving
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Katy
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: Alexandria
country: United States
facility: Novo Nordisk Investigational Site
state: Virginia
city: Buenos Aires
country: Argentina
facility: Novo Nordisk Investigational Site
city: Buenos Aires
country: Argentina
facility: Novo Nordisk Investigational Site
city: Caba
country: Argentina
facility: Novo Nordisk Investigational Site
city: Lanus Este
country: Argentina
facility: Novo Nordisk Investigational Site
city: Mar del Plata
country: Argentina
facility: Novo Nordisk Investigational Site
city: Karlovac
country: Croatia
facility: Novo Nordisk Investigational Site
city: Osijek
country: Croatia
facility: Novo Nordisk Investigational Site
city: Slavonski Brod
country: Croatia
facility: Novo Nordisk Investigational Site
city: Virovitica
country: Croatia
facility: Novo Nordisk Investigational Site
city: Zagreb
country: Croatia
facility: Novo Nordisk Investigational Site
city: Helsinki
country: Finland
facility: Novo Nordisk Investigational Site
city: Helsinki
country: Finland
facility: Novo Nordisk Investigational Site
city: Kerava
country: Finland
facility: Novo Nordisk Investigational Site
city: Oulu
country: Finland
facility: Novo Nordisk Investigational Site
city: Turku
country: Finland
facility: Novo Nordisk Investigational Site
city: Chalons-en-Champagne Cedex
country: France
facility: Novo Nordisk Investigational Site
city: Corbeil Essonnes
country: France
facility: Novo Nordisk Investigational Site
city: LA ROCHELLE cedex
country: France
facility: Novo Nordisk Investigational Site
city: Le Creusot
country: France
facility: Novo Nordisk Investigational Site
city: Nanterre
country: France
facility: Novo Nordisk Investigational Site
city: Roubaix
country: France
facility: Novo Nordisk Investigational Site
city: Strasbourg
country: France
facility: Novo Nordisk Investigational Site
city: Venissieux
country: France
facility: Novo Nordisk Investigational Site
city: Dresden
country: Germany
facility: Novo Nordisk Investigational Site
city: Dresden
country: Germany
facility: Novo Nordisk Investigational Site
city: Duisburg
country: Germany
facility: Novo Nordisk Investigational Site
city: Hohenmölsen
country: Germany
facility: Novo Nordisk Investigational Site
city: Mannheim
country: Germany
facility: Novo Nordisk Investigational Site
city: Oldenburg
country: Germany
facility: Novo Nordisk Investigational Site
city: Rehlingen-Siersburg
country: Germany
facility: Novo Nordisk Investigational Site
city: Völklingen
country: Germany
facility: Novo Nordisk Investigational Site
city: Athens
country: Greece
facility: Novo Nordisk Investigational Site
city: Athens
country: Greece
facility: Novo Nordisk Investigational Site
city: Athens
country: Greece
facility: Novo Nordisk Investigational Site
city: Piraeus
country: Greece
facility: Novo Nordisk Investigational Site
city: Thessaloniki
country: Greece
facility: Novo Nordisk Investigational Site
city: Thessaloniki
country: Greece
facility: Novo Nordisk Investigational Site
city: Bologna
country: Italy
facility: Novo Nordisk Investigational Site
city: Città di Castello
country: Italy
facility: Novo Nordisk Investigational Site
city: Milano
country: Italy
facility: Novo Nordisk Investigational Site
city: Palermo
country: Italy
facility: Novo Nordisk Investigational Site
city: Pavia
country: Italy
facility: Novo Nordisk Investigational Site
city: Roma
country: Italy
facility: Novo Nordisk Investigational Site
city: Siena
country: Italy
facility: Novo Nordisk Investigational Site
city: Amsterdam
country: Netherlands
facility: Novo Nordisk Investigational Site
city: Apeldoorn
country: Netherlands
facility: Novo Nordisk Investigational Site
city: Delft
country: Netherlands
facility: Novo Nordisk Investigational Site
city: Hoofddorp
country: Netherlands
facility: Novo Nordisk Investigational Site
city: Leeuwarden
country: Netherlands
facility: Novo Nordisk Investigational Site
city: Rotterdam
country: Netherlands
facility: Novo Nordisk Investigational Site
city: Rotterdam
country: Netherlands
facility: Novo Nordisk Investigational Site
city: Venlo
country: Netherlands
facility: Novo Nordisk Investigational Site
city: Zoetermeer
country: Netherlands
facility: Novo Nordisk Investigational Site
city: Caguas
country: Puerto Rico
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: 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: Basel
country: Switzerland
facility: Novo Nordisk Investigational Site
city: Genève 14
country: Switzerland
facility: Novo Nordisk Investigational Site
city: Luzern 16
country: Switzerland
facility: Novo Nordisk Investigational Site
city: St. Gallen
country: Switzerland
facility: Novo Nordisk Investigational Site
city: Zollikerberg
country: Switzerland
facility: Novo Nordisk Investigational Site
city: Ayr
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Bath
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Bradford-on-Avon
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Haxey
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Headington
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Rotherham
country: United Kingdom
facility: Novo Nordisk Investigational Site
Study officials:
affiliation: Novo Nordisk A/S
name: Global Clinical Registry (GCR, 1452)
role: STUDY_DIRECTOR
References:
citation: Fonseca VA, Capehorn MS, Garg SK, Jodar 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 Sep 1;104(9):4078-4086. doi: 10.1210/jc.2018-02685.
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: Ahmann AJ, Capehorn M, Charpentier G, Dotta F, Henkel E, Lingvay I, Holst AG, Annett MP, Aroda VR. Efficacy and Safety of Once-Weekly Semaglutide Versus Exenatide ER in Subjects With Type 2 Diabetes (SUSTAIN 3): A 56-Week, Open-Label, Randomized Clinical Trial. Diabetes Care. 2018 Feb;41(2):258-266. doi: 10.2337/dc17-0417. Epub 2017 Dec 15.
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: 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.
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: 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.
citation: Malkin SJP, Russel-Szymczyk M, Liidemann G, Volke V, Hunt B. Once-Weekly Semaglutide Versus Once-Daily Liraglutide for the Treatment of Type 2 Diabetes: A Long-Term Cost-Effectiveness Analysis in Estonia. Diabetes Ther. 2019 Feb;10(1):159-176. doi: 10.1007/s13300-018-0542-x. Epub 2018 Dec 7.
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: Overgaard RV, Lindberg SO, 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.
citation: Mosenzon O, Capehorn MS, De Remigis A, Rasmussen S, Weimers P, Rosenstock J. Impact of semaglutide on high-sensitivity C-reactive protein: exploratory patient-level analyses of SUSTAIN and PIONEER randomized clinical trials. Cardiovasc Diabetol. 2022 Sep 2;21(1):172. doi: 10.1186/s12933-022-01585-7.
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: Lingvay I, Capehorn MS, Catarig AM, Johansen P, Lawson J, Sandberg A, Shaw R, Paine A. Efficacy of Once-Weekly Semaglutide vs Empagliflozin Added to Metformin in Type 2 Diabetes: Patient-Level Meta-analysis. J Clin Endocrinol Metab. 2020 Dec 1;105(12):e4593-604. doi: 10.1210/clinem/dgaa577.
citation: Capehorn M, Ghani Y, Hindsberger C, Johansen P, Jodar E. Once-Weekly Semaglutide Reduces HbA1c and Body Weight in Patients with Type 2 Diabetes Regardless of Background Common OAD: a Subgroup Analysis from SUSTAIN 2-4 and 10. Diabetes Ther. 2020 May;11(5):1061-1075. doi: 10.1007/s13300-020-00796-z. Epub 2020 Mar 19.
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.