Clinical trial NCT00637273: A Study to Compare the Glycemic Effects, Safety, and Tolerability of Exenatide Once Weekly to Those of Sitagliptin and Pioglitazone,in Subjects With Type 2 Diabetes Treated With Metformin (DURATION - 2)
Official title: A Randomized, Double-Blind, Parallel-Group, Multicenter Study to Compare the Glycemic Effects, Safety, and Tolerability of Exenatide Long-Acting Release(Once Weekly) to Those of Sitagliptin and a Thiazolidinedione in Subjects With Type 2 Diabetes Mellitus Treated With Metformin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Keywords: diabetes
exenatide once weekly
Byetta
sitagliptin
Januvia
thiazolidinedione
Amylin
Lilly
Pioglitazone
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
Collaborators: name: Eli Lilly and Company
First posted: 2008-03-17
Enrollment: 514
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 study will compare the benefits of exenatide once weekly treatment to those achieved by the approved antidiabetic therapies sitagliptin and pioglitazone in subjects whose type 2 diabetes is managed with metformin therapy alone. The safety and tolerability of the three treatment regimens will also be compared.


Eligibility criteria: Inclusion Criteria:

* Has been diagnosed with type 2 diabetes mellitus
* Has a hemoglobin-specific A1c fraction (HbA1c) of 7.1% to 11.0%, inclusive, at study start
* Has a body mass index (BMI)of 25 kg/m2 to 45 kg/m2, inclusive, at study start
* Has been on a stable treatment regimen of metformin for a minimum of 2 months prior to study start
* Either is not treated with or has been on a stable treatment regimen with any of the following medications for a minimum of 2 months prior to study start:

  1. Hormone replacement therapy (female subjects)
  2. Oral contraceptives (female subjects)
  3. Antihypertensive agents
  4. Lipid-lowering agents
  5. Thyroid replacement therapy
  6. Antidepressant agents
  7. Drugs known to affect body weight, including prescription medications (e.g. orlistat \[XENICAL®\], sibutramine \[MERIDIA®\], topiramate \[TOPAMAX®\]) and over-the-counter antiobesity agents

Exclusion Criteria:

* Has been previously exposed to exenatide once weekly
* Has donated blood within 60 days of study start or is planning to donate blood during the study
* Currently being treated, or is expected to require or undergo treatment with any of the following treatment-excluded medications:

  1. Exenatide (BYETTA®) or any Dipeptidyl peptidase-4 DPP-4)inhibitor, sulfonylurea (SU), thiazolidinedione (TZD), or glucagon-like peptide (GLP)-1 analog within 3 months prior to study start
  2. Alpha-glucosidase inhibitor, meglitinide, nateglinide, or pramlintide (SYMLIN®) within 30 days of study start
  3. Insulin within 2 weeks of study start or for more than 1 week within 3 months of study start
  4. Systemic corticosteroids by oral, intravenous, or intramuscular route; or potent, inhaled, or intrapulmonary (including ADVAIR®) steroids known to have a high rate of systemic absorption
  5. Drugs interacting with the CYP2C8 enzyme system, including gemfibrozil (LOPID®) and rifampin
* Has received any investigational drug within 1 month (or five half-lives of investigational drug, whichever is greater) of study start
* Has previously experienced a clinically significant adverse event (e.g., significant edema) related to TZD or DPP-4 inhibitor use

Primary outcomes:
measure: Change in HbA1c From Baseline to Week 26
timeFrame: Day 1, Week 26
Secondary outcomes:
measure: Percentage of Subjects Achieving HbA1c Target of <7% at Week 26
timeFrame: Week 26
measure: Percentage of Subjects Achieving HbA1c Target of <=6.5% at Week 26
timeFrame: Week 26
measure: Percentage of Subjects Achieving HbA1c Target of <=6.0% at Week 26
timeFrame: Week 26
measure: Change in Body Weight From Baseline to Week 26
timeFrame: Day 1, Week 26
measure: Change in Fasting Plasma Glucose From Baseline to Week 26
timeFrame: Day 1, Week 26
measure: Change in Systolic Blood Pressure From Baseline to Week 26
timeFrame: Day 1, Week 26
measure: Change in Diastolic Blood Pressure From Baseline to Week 26
timeFrame: Day 1, Week 26
measure: Change in Fasting Total Cholesterol From Baseline to Week 26
timeFrame: Day 1, Week 26
measure: Change in Fasting High-density Lipoprotein (HDL) From Baseline to Week 26
timeFrame: Day 1, Week 26
measure: Ratio of Fasting Triglycerides at Week 26 to Baseline
timeFrame: Day 1, Week 26
measure: Assessment on Event Rate of Treatment-emergent Hypoglycemic Events
timeFrame: Day 1 to Week 26
Other outcomes:
Locations:
city: Peoria
country: United States
facility: Research Site
state: Arizona
city: Artesia
country: United States
facility: Research Site
state: California
city: Concord
country: United States
facility: Research Site
state: California
city: Encino
country: United States
facility: Research Site
state: California
city: Greenbrae
country: United States
facility: Research Site
state: California
city: La Mesa
country: United States
facility: Research Site
state: California
city: Orange
country: United States
facility: Research Site
state: California
city: Walnut Creek
country: United States
facility: Research Site
state: California
city: Whittier
country: United States
facility: Research Site
state: California
city: Colorado Springs
country: United States
facility: Research Site
state: Colorado
city: Washington
country: United States
facility: Research Site
state: District of Columbia
city: Coral Gables
country: United States
facility: Research Site
state: Florida
city: Deland
country: United States
facility: Research Site
state: Florida
city: Melbourne
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: New Port Richey
country: United States
facility: Research Site
state: Florida
city: Decatur
country: United States
facility: Research Site
state: Georgia
city: Avon
country: United States
facility: Research Site
state: Indiana
city: Wichita
country: United States
facility: Research Site
state: Kansas
city: Paducah
country: United States
facility: Research Site
state: Kentucky
city: Baton Rouge
country: United States
facility: Research Site
state: Louisiana
city: New Orleans
country: United States
facility: Research Site
state: Louisiana
city: Oxon Hill
country: United States
facility: Research Site
state: Maryland
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Chelsea
country: United States
facility: Research Site
state: Michigan
city: Ypsilanti
country: United States
facility: Research Site
state: Michigan
city: St. Louis Park
country: United States
facility: Research Site
state: Minnesota
city: St. Louis
country: United States
facility: Research Site
state: Missouri
city: Butte
country: United States
facility: Research Site
state: Montana
city: Lincoln
country: United States
facility: Research Site
state: Nebraska
city: Las Vegas
country: United States
facility: Research Site
state: Nevada
city: New Hyde Park
country: United States
facility: Research Site
state: New York
city: New Windsor
country: United States
facility: Research Site
state: New York
city: New York
country: United States
facility: Research Site
state: New York
city: Rochester
country: United States
facility: Research Site
state: New York
city: Durham
country: United States
facility: Research Site
state: North Carolina
city: Statesville
country: United States
facility: Research Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Research Site
state: North Carolina
city: Athens
country: United States
facility: Research Site
state: Ohio
city: Cincinnati
country: United States
facility: Research Site
state: Ohio
city: Dayton
country: United States
facility: Research Site
state: Ohio
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Rapid City
country: United States
facility: Research Site
state: South Dakota
city: Memphis
country: United States
facility: Research Site
state: Tennessee
city: Austin
country: United States
facility: Research Site
state: Texas
city: Dallas
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Richmond
country: United States
facility: Research Site
state: Virginia
city: Olympia
country: United States
facility: Research Site
state: Washington
city: Spokane
country: United States
facility: Research Site
state: Washington
city: Tacoma
country: United States
facility: Research Site
state: Washington
city: Bangalore
country: India
facility: Research Site
city: Indore
country: India
facility: Research Site
city: Karnal
country: India
facility: Research Site
city: Mumbai
country: India
facility: Research Site
city: Pune
country: India
facility: Research Site
city: Mexico City
country: Mexico
facility: Research Site
state: Distrito Federal
city: Guadalajara
country: Mexico
facility: Research Site
state: Jalisco
city: Zapopan
country: Mexico
facility: Research Site
state: Jalisco
city: Cuernavaca
country: Mexico
facility: Research Site
state: Morelos
city: Monterrey
country: Mexico
facility: Research Site
state: NuevoLeon
city: Toluca
country: Mexico
facility: Research Site
Study officials:
affiliation: Amylin Pharmaceuticals, LLC.
name: Lisa Porter, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Malloy J, Meloni A, Han J. Efficacy and tolerability of exenatide once weekly versus sitagliptin in patients with type 2 diabetes mellitus: a retrospective analysis of pooled clinical trial data. Postgrad Med. 2013 May;125(3):58-67. doi: 10.3810/pgm.2013.05.2661.
citation: 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.
citation: 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.
citation: Peyrot M, Bushnell DM, Best JH, Martin ML, Cameron A, Patrick DL. Development and validation of the self-management profile for type 2 diabetes (SMP-T2D). Health Qual Life Outcomes. 2012 Oct 5;10:125. doi: 10.1186/1477-7525-10-125.
citation: 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.
citation: Wysham C, Bergenstal R, Malloy J, Yan P, Walsh B, Malone J, Taylor K. DURATION-2: efficacy and safety of switching from maximum daily sitagliptin or pioglitazone to once-weekly exenatide. Diabet Med. 2011 Jun;28(6):705-14. doi: 10.1111/j.1464-5491.2011.03301.x.
citation: Bergenstal RM, Wysham C, Macconell L, Malloy J, Walsh B, Yan P, Wilhelm K, Malone J, Porter LE; DURATION-2 Study Group. Efficacy and safety of exenatide once weekly versus sitagliptin or pioglitazone as an adjunct to metformin for treatment of type 2 diabetes (DURATION-2): a randomised trial. Lancet. 2010 Aug 7;376(9739):431-9. doi: 10.1016/S0140-6736(10)60590-9. Epub 2010 Jun 26.