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)
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: exenatide once weekly; sitagliptin; pioglitazone; placebo tablet; placebo once weekly
Intervention description: subcutaneous injection, 2.0mg, once a week; oral tablet, 100mg, once a day; oral tablet, 45mg, once a day; oral tablet, once a day; subcutaneous injection, once a week
Intervention MeSH terms: Pioglitazone; Sitagliptin Phosphate; Exenatide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 514.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: diabetes; exenatide once weekly; Byetta; sitagliptin; Januvia; thiazolidinedione; Amylin; Lilly; Pioglitazone

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