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)

Phase 3

Completed

Conditions: Type 2 Diabetes Mellitus

Interventions: Drug: exenatide once weekly
Drug: sitagliptin
Drug: pioglitazone
Drug: placebo tablet
Drug: placebo once weekly

Registration Number: NCT00637273

Lead Sponsor: AstraZeneca

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 514

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	exenatide once weekly	-
2	sitagliptin	-
1	placebo tablet	-
3	placebo once weekly	-
2	placebo once weekly	-
3	pioglitazone	-

Primary Outcome Measures

Name	Time	Method
Change in HbA1c From Baseline to Week 26	Day 1, Week 26	Absolute change in HbA1c from baseline (Day 1) to Week 26 \[Week 26 - Baseline\].

Secondary Outcome Measures

Name	Time	Method
Percentage of Subjects Achieving HbA1c Target of <7% at Week 26	Week 26	Percentages of subjects achieving HbA1c target values of \<7% at Week 26.
Percentage of Subjects Achieving HbA1c Target of <=6.0% at Week 26	Week 26	Percentages of subjects achieving HbA1c target values of \<=6.0% at Week 26.
Change in Body Weight From Baseline to Week 26	Day 1, Week 26	Change in body weight from baseline (Day 1) to Week 26.
Change in Fasting High-density Lipoprotein (HDL) From Baseline to Week 26	Day 1, Week 26	Change in fasting HDL from baseline (Day 1) to Week 26.
Percentage of Subjects Achieving HbA1c Target of <=6.5% at Week 26	Week 26	Percentages of subjects achieving HbA1c target values of \<=6.5% at Week 26.
Change in Fasting Plasma Glucose From Baseline to Week 26	Day 1, Week 26	Change in fasting plasma glucose from baseline (Day 1) to Week 26.
Change in Systolic Blood Pressure From Baseline to Week 26	Day 1, Week 26	Change in systolic blood pressure from baseline (Day 1) to Week 26.
Change in Diastolic Blood Pressure From Baseline to Week 26	Day 1, Week 26	Change in diastolic blood pressure from baseline (Day 1) to Week 26.
Change in Fasting Total Cholesterol From Baseline to Week 26	Day 1, Week 26	Change in fasting total cholesterol from baseline (Day 1) to Week 26.
Assessment on Event Rate of Treatment-emergent Hypoglycemic Events	Day 1 to Week 26	Major hypoglycemia: events that, in the judgment of the investigator or physician, resulted in loss of consciousness, seizure, coma, or other change in mental status consistent with neuroglycopenia, in which symptoms resolved after administration of intramuscular glucagon or intravenous glucose, required third-party assistance, and was accompanied by a blood glucose concentration \< 54 mg/dL prior to treatment. Minor hypoglycemia: symptoms consistent with hypoglycemia and blood glucose concentration \< 54 mg/dL prior to treatment and not classified as major hypoglycemia.
Ratio of Fasting Triglycerides at Week 26 to Baseline	Day 1, Week 26	Ratio of triglycerides (measured in mg/dL) at Week 26 to baseline (Day 1). Log (Postbaseline Triglycerides) - log (Baseline Triglycerides); change from baseline to endpoint is presented as ratio of endpoint to baseline.