Effect on Weight Loss of Exenatide Versus Placebo

• Change in Glycosylated Hemoglobin (HbA1c) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Change in HbA1c from baseline after 24 weeks of treatment (i.e., HbA1c at week 24 minus HbA1c at week 0)
• Change in 6-point Self Monitored Blood Glucose (SMBG) Profile. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Change in SMBG at each of 6 time points throughout a day (blood glucose measurements before and 2 hours after the start of the morning, mid-day, and evening meals); week 24 compared to week 0 (i.e., SMBG at week 24 minus SMBG at week 0)
• Change in Waist Circumference. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Change in waist circumference from baseline after 24 weeks of treatment (i.e., waist circumference at week 24 minus waist circumference at week 0)
• Change in Homeostatic Model Assessment-Beta Cell (HOMA-B) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Ratio of HOMA-B at week 24 to HOMA-B at week 0 (i.e., HOMA-B at week 24 divided by HOMA-B at week 0). HOMA-B is a measure of beta cell function.
• Change in Homeostatic Model Assessment-Insulin Sensitivity (HOMA-S) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Ratio of HOMA-S at week 24 to HOMA-S at week 0 (i.e., HOMA-S at week 24 divided by HOMA-S at week 0). HOMA-S is a measure of insulin sensitivity.
• Change in High Density Lipoprotein (HDL) Cholesterol [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Change in HDL cholesterol from baseline after 24 weeks of treatment (i.e., HDL cholesterol at week 24 minus HDL cholesterol at week 0)
• Change in Low Density Lipoprotein (LDL) Cholesterol [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Change in LDL cholesterol from baseline after 24 weeks of treatment (i.e., LDL cholesterol at week 24 minus LDL cholesterol at week 0)
• Change in Total Cholesterol [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Change in total cholesterol from baseline after 24 weeks of treatment (i.e., total cholesterol at week 24 minus total cholesterol at week 0)
• Change in Triglycerides [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Ratio of triglyceride levels at week 24 to triglyceride levels at week 0 (i.e., triglycerides at week 24 divided by triglycerides at week 0)
• Incidence of Hypoglycemic Events [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Number of patients experiencing one or more events of hypoglycemia at any point in the study
• Rate of Hypoglycemic Events [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Overall rate of hypoglycemia, adjusted for 1 year (i.e., events of hypoglycemia per patient per year)

This trial is designed to compare the effects of twice-daily exenatide and twice-daily placebo on weight loss. This trial will evaluate overweight and obese subjects with type 2 diabetes who have inadequate glycemic control with metformin, sulfonylurea, or metformin plus a sulfonylurea. Subjects will be treated with exenatide or placebo in addition to their current oral antidiabetes agent regimen and participate in a lifestyle modification program.

• Drug: exenatide
  subcutaneous injection, 5mcg or 10mcg, twice a day
  Other Name: Byetta
• Drug: placebo
  subcutaneous injection, volume equivalent to exenatide dose, twice a day

• Experimental: Group A
  Intervention: Drug: exenatide
• Placebo Comparator: Group B
  Intervention: Drug: placebo

Inclusion Criteria:

• Diagnosed with type 2 diabetes for at least 6 months
• Have been treated with a stable dose of the following for at least 6 weeks prior to screening: *immediate or extended release metformin, or *a sulfonylurea, or *a fixed-dose sulfonylurea/metformin combination therapy
• Have an HbA1c of 6.6% to 10.0%, inclusive
• Have a Body Mass Index (BMI) of 25 kg/m^2 to 39.9 kg/m^2, inclusive

Exclusion Criteria:

• Are treated with any of the following excluded medications: *exogenous insulin, thiazolidinedione, or alpha-glucosidase inhibitor for more than 1 week within 6 weeks of screening; *Symlin injection at any time; * Byetta injection within 3 months of screening or discontinuation of therapy at any time due to adverse reaction; *drugs that directly affect gastrointestinal motility; *use of a weight loss drug (including those available over the counter) within 3 months of screening; *chronic (lasting longer than 2 weeks) systemic corticosteroids (excluding topical, intranasal, and inhaled preparations) by oral, intravenous, or intramuscular route within 2 months of screening
• Have conditions contraindicating metformin and/or sulfonylurea use
• Have had a change in lipid-lowering agents within 6 weeks of screening
• Have received glucagon-like peptide-1 (GLP-1) analogs, or dipeptidyl peptidase-IV inhibitors (DPP-IV inhibitors) or have previously participated in this study
• 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