Efficacy of Exenatide Once Weekly and Once-Daily Insulin Glargine in Patients With Type 2 Diabetes Treated With Metformin Alone or in Combination With Sulfonylurea (DURATION - 3)

NCT ID: NCT00641056

Last Updated: 2015-06-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 467 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-04-30
• Study Completion Date: 2009-11-30

Brief Summary

The purpose of this study is to compare the effects of 2.0 mg exenatide once weekly and insulin glargine, titrated to glucose targets using the algorithm described by Yki- Järvinen et al.(2007), with respect to glycemic improvements, body weight, fasting lipids, safety, and tolerability.

Conditions

Type 2 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Group Type: EXPERIMENTAL

Exenatide Once Weekly

Intervention Type: DRUG

subcutaneous injection, 2.0mcg, once weekly

2

Group Type: ACTIVE_COMPARATOR

Insulin Glargine

Intervention Type: DRUG

subcutaneous injection, variable dose, QD

Interventions

Exenatide Once Weekly

subcutaneous injection, 2.0mcg, once weekly

Intervention Type: DRUG

Insulin Glargine

subcutaneous injection, variable dose, QD

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Has type 2 diabetes and at least 18 years of age at screening.
• Hemoglobin A1c (HbA1c) of 7.1% to 11.0%, inclusive, at screening.
• Body mass index (BMI) of 25 kg/m2 to 45 kg/m2, inclusive, at screening.
• Have a history of stable body weight (not varying by >5% for at least 3 months prior to screening).
• Have been treated with metformin(Met) for at least 3 months and have been taking a stable dose for at least 8 weeks prior to screening OR
• Have been treated with metformin(Met) for at least 3 months and have been taking a stable dose for at least 8 weeks prior to screening and have been treated with SU for at least 3 months and have been taking a stable dose of at least an optimally effective dose of brand of SU for 8 weeks prior to screening.

Exclusion Criteria

• Have had a clinically significant history of cardiac disease or presence of active cardiac disease within the year prior to inclusion in the study, including myocardial infarction, clinically significant arrhythmia, unstable angina, moderate to severe congestive heart failure, coronary artery bypass surgery, or angioplasty; or is expected to require coronary artery bypass surgery or angioplasty during the course of the study.
• Have clinical signs or symptoms of liver disease, acute or chronic hepatitis.
• Have a history of renal transplantation or are currently receiving renal dialysis.
• Have active or untreated malignancy, or have been in remission from clinically significant malignancy (other than basal cell or squamous cell skin cancer, in situ carcinomas of the cervix, or in situ prostate cancer) for less than 5 years.
• Have had greater than three episodes of major hypoglycemia within 6 months prior to screening.
• Have any contraindication for the oral antidiabetic agent which they use.
• Have a known allergy or hypersensitivity to insulin glargine, exenatide once weekly, or excipients contained in these agents.
• Are known to have active proliferative retinopathy.
• Have been treated with drugs that promote weight loss (e.g., Xenical® [orlistat], Meridia® [sibutramine], Acomplia® [rimonabant], Acutrim® [phenylpropanolamine], or similar over-the-counter medications) within 3 months of screening.
• Have been treated for longer than 2 weeks with any of the following excluded medications within 3 months prior to screening:

• Insulin
• Thiazolidinediones (e.g., Actos® [pioglitazone] or Avandia® [rosiglitazone])
• Alpha-glucosidase inhibitors (e.g., Glyset® [miglitol] or Precose® [acarbose])
• Meglitinides (e.g., Prandin® [repaglinide] or Starlix® [nateglinide]).
• Byetta® (exenatide BID formulation)
• Dipeptidyl peptidase (DPP)-4 inhibitors (e.g., Januvia™ [sitagliptin], Galvus® [vildagliptin])
• Symlin® (pramlintide acetate).
• Have had an organ transplant.
• Have donated blood within 30 days of screening.
• Have previously completed or withdrawn from this study or any other study investigating exenatide once weekly.
• Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry.
• Are currently enrolled in any other clinical study.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: collaborator

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Chief Medical Officer, MD

Role: STUDY_DIRECTOR

Eli Lilly and Company

Locations

Research Site

Escondido, California, United States

Research Site

Jacksonville, Florida, United States

Research Site

Orlando, Florida, United States

Research Site

West Palm Beach, Florida, United States

Research Site

Honolulu, Hawaii, United States

Research Site

Idaho Falls, Idaho, United States

Research Site

Minneapolis, Minnesota, United States

Research Site

St Louis, Missouri, United States

Research Site

Dayton, Ohio, United States

Research Site

Ada, Oklahoma, United States

Research Site

San Antonio, Texas, United States

Research Site

Spokane, Washington, United States

Research Site

Wollongong, New South Wales, Australia

Research Site

Herston, Queensland, Australia

Research Site

Adelaide, South Australia, Australia

Research Site

Keswick, South Australia, Australia

Research Site

Box Hill, Victoria, Australia

Research Site

Geelong, Victoria, Australia

Research Site

Brussels, , Belgium

Research Site

Edegem, , Belgium

Research Site

Mělník, , Czechia

Research Site

Prague, , Czechia

Research Site

Stodůlky, , Czechia

Research Site

Aalborg, , Denmark

Research Site

Arhus C, , Denmark

Research Site

Herlev, , Denmark

Research Site

Køge, , Denmark

Research Site

Angers, , France

Research Site

Corbeil Essoness, , France

Research Site

Nancy, , France

Research Site

Nanterre, , France

Research Site

Toulouse, , France

Research Site

Bad Mergentheim, , Germany

Research Site

Dresden, , Germany

Research Site

Essen, , Germany

Research Site

Falkensee, , Germany

Research Site

Fulda, , Germany

Research Site

Münster, , Germany

Research Site

Othmarschen, , Germany

Research Site

Rothenburg An Der Fulda, , Germany

Research Site

Speyer, , Germany

Research Site

Athens, , Greece

Research Site

Thessaloniki, , Greece

Research Site

Budapest, , Hungary

Research Site

Eger, , Hungary

Research Site

Gyula, , Hungary

Research Site

Pécs, , Hungary

Research Site

Mexico City, , Mexico

Research Site

Mérida, , Mexico

Research Site

Tampico, , Mexico

Research Site

Tijuana, , Mexico

Research Site

Amsterdam, , Netherlands

Research Site

Gouda, , Netherlands

Research Site

Hoogeveen, , Netherlands

Research Site

Rotterdam, , Netherlands

Research Site

Zwijndrecht, , Netherlands

Research Site

Zwolle, , Netherlands

Research Site

Caguas, , Puerto Rico

Research Site

Yabucoa, , Puerto Rico

Research Site

Moscow, , Russia

Research Site

Rostov-on-Don, , Russia

Research Site

Saint Petersburg, , Russia

Research Site

Gyeonggi-do, , South Korea

Research Site

Seoul, , South Korea

Research Site

Alicante, , Spain

Research Site

Alzira-Valencia, , Spain

Research Site

Barcelona, , Spain

Research Site

Bilbao, , Spain

Research Site

Madrid, , Spain

Research Site

Málaga, , Spain

Research Site

Teruel, , Spain

Research Site

Chiayi City, , Taiwan

Research Site

Tainan County, , Taiwan

Research Site

Taipei, , Taiwan

Research Site

Taoyuan District, , Taiwan

Countries

United States; Australia; Belgium; Czechia; Denmark; France; Germany; Greece; Hungary; Mexico; Netherlands; Puerto Rico; Russia; South Korea; Spain; Taiwan

References

Diamant M, Van Gaal L, Stranks S, Guerci B, MacConell L, Haber H, Scism-Bacon J, Trautmann M. Safety and efficacy of once-weekly exenatide compared with insulin glargine titrated to target in patients with type 2 diabetes over 84 weeks. Diabetes Care. 2012 Apr;35(4):683-9. doi: 10.2337/dc11-1233. Epub 2012 Feb 22.

Reference Type: RESULT

PMID: 22357185 (View on PubMed)

Guja C, Frias JP, Suchower L, Hardy E, Marr G, Sjostrom CD, Jabbour SA. Safety and Efficacy of Exenatide Once Weekly in Participants with Type 2 Diabetes and Stage 2/3 Chronic Kidney Disease. Diabetes Ther. 2020 Jul;11(7):1467-1480. doi: 10.1007/s13300-020-00815-z. Epub 2020 Apr 18.

Reference Type: DERIVED

PMID: 32306296 (View on PubMed)

Diamant M, Van Gaal L, Guerci B, Stranks S, Han J, Malloy J, Boardman MK, Trautmann ME. Exenatide once weekly versus insulin glargine for type 2 diabetes (DURATION-3): 3-year results of an open-label randomised trial. Lancet Diabetes Endocrinol. 2014 Jun;2(6):464-73. doi: 10.1016/S2213-8587(14)70029-4. Epub 2014 Apr 4.

Reference Type: DERIVED

PMID: 24731672 (View on PubMed)

Grimm M, Han J, Weaver C, Griffin P, Schulteis CT, Dong H, Malloy J. Efficacy, safety, and tolerability of exenatide once weekly in patients with type 2 diabetes mellitus: an integrated analysis of the DURATION trials. Postgrad Med. 2013 May;125(3):47-57. doi: 10.3810/pgm.2013.05.2660.

Reference Type: DERIVED

PMID: 23748506 (View on PubMed)

Meloni AR, DeYoung MB, Han J, Best JH, Grimm M. Treatment of patients with type 2 diabetes with exenatide once weekly versus oral glucose-lowering medications or insulin glargine: achievement of glycemic and cardiovascular goals. Cardiovasc Diabetol. 2013 Mar 23;12:48. doi: 10.1186/1475-2840-12-48.

Reference Type: DERIVED

PMID: 23522121 (View on PubMed)

Fineman MS, Mace KF, Diamant M, Darsow T, Cirincione BB, Booker Porter TK, Kinninger LA, Trautmann ME. Clinical relevance of anti-exenatide antibodies: safety, efficacy and cross-reactivity with long-term treatment. Diabetes Obes Metab. 2012 Jun;14(6):546-54. doi: 10.1111/j.1463-1326.2012.01561.x. Epub 2012 Feb 10.

Reference Type: DERIVED

PMID: 22236356 (View on PubMed)

Diamant M, Van Gaal L, Stranks S, Northrup J, Cao D, Taylor K, Trautmann M. Once weekly exenatide compared with insulin glargine titrated to target in patients with type 2 diabetes (DURATION-3): an open-label randomised trial. Lancet. 2010 Jun 26;375(9733):2234-43. doi: 10.1016/S0140-6736(10)60406-0.

Reference Type: DERIVED

PMID: 20609969 (View on PubMed)

Other Identifiers

H8O-MC-GWBR (DURATION - 3)

Identifier Type: -

Identifier Source: org_study_id