Phase 3
N=514
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)
Type 2 Diabetes Mellitus
Bottom Line
View on ClinicalTrials.gov: NCT00637273 ↗Enrolled (actual)
514
Serious AEs
3.9%
Results posted
Jun 2012
Primary outcome: Primary: Change in HbA1c From Baseline to Week 26 — -1.55; -0.92; -1.23 percentage of total hemoglobin — p=<.0001
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- exenatide once weekly (Drug); sitagliptin (Drug); pioglitazone (Drug); placebo tablet (Drug); placebo once weekly (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- AstraZeneca
- Primary completion
- Feb 2009
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in HbA1c From Baseline to Week 26 |
-1.55; -0.92; -1.23 | <.0001 sig |
| SECONDARY Percentage of Subjects Achieving HbA1c Target of <7% at Week 26 |
58.8; 30.7; 43.6 | <.0001 sig |
| SECONDARY Percentage of Subjects Achieving HbA1c Target of <=6.5% at Week 26 |
38.8; 15.7; 26.7 | <.0001 sig |
| SECONDARY Percentage of Subjects Achieving HbA1c Target of <=6.0% at Week 26 |
13.8; 9.0; 4.8 | 0.1700 |
| SECONDARY Change in Body Weight From Baseline to Week 26 |
-2.31; -0.77; 2.79 | 0.0002 sig |
| SECONDARY Change in Fasting Plasma Glucose From Baseline to Week 26 |
-31.8; -16.3; -27.3 | 0.0038 sig |
| SECONDARY Change in Systolic Blood Pressure From Baseline to Week 26 |
-3.6; 0.2; -1.6 | 0.0055 sig |
| SECONDARY Change in Diastolic Blood Pressure From Baseline to Week 26 |
-1.4; -0.4; -2.5 | 0.1685 |
| SECONDARY Change in Fasting Total Cholesterol From Baseline to Week 26 |
-0.6; 3.1; 6.2 | 0.2686 |
| SECONDARY Change in Fasting High-density Lipoprotein (HDL) From Baseline to Week 26 |
2.0; 2.0; 6.2 | 0.9546 |
| SECONDARY Ratio of Fasting Triglycerides at Week 26 to Baseline |
0.95; 0.95; 0.84 | 0.9718 |
| SECONDARY Assessment on Event Rate of Treatment-emergent Hypoglycemic Events |
0.00; 0.00; 0.00; 0.03; 0.12; 0.01 | — |
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:
- Hormone replacement therapy (female subjects)
- Oral contraceptives (female subjects)
- Antihypertensive agents
- Lipid-lowering agents
- Thyroid replacement therapy
- Antidepressant agents
- 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:
- 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
- Alpha-glucosidase inhibitor, meglitinide, nateglinide, or pramlintide (SYMLIN®) within 30 days of study start
- Insulin within 2 weeks of study start or for more than 1 week within 3 months of study start
- 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
- 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
Data sourced from ClinicalTrials.gov (NCT00637273). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.