How Glargine Insulin, Oral Diabetes Medications and Exenatide May Improve Blood Sugar Control and Weight Gain in Type 2 Diabetics

Inclusion Criteria: * Male or female patients with type 2 diabetes * Taking metformin at least 1000 mg daily plus a secretagogue, an alpha glucosidase inhibitor, a thiazolidinedione, or a single injection of any kind of insulin up to 0.4 units/kg daily for \> 3 months * Age range 30 to 70 years * Body mass index 25-45 kg/m2 * HbA1c 7.0 to 10.0% (or 7.0 to 8.5% if the second antihyperglycemic agent is insulin) * Less than 50% of randomized participants will have used insulin previously Exclusion Criteria: * Use of more than two antihyperglycemic agents within the last 3 months * Use of more than one daily injection of any kind of insulin in the last 3 months * Positive anti-GAD antibody (test required in screening) * Fasting C-peptide \<0.5 ng/mL (test required in screening) * Pregnancy (test required in screening if able to conceive) or lactation * Excessive use of alcohol or evidence of other form of drug dependency * Unwillingness or inability to grant informed consent * Unwillingness or inability to perform self-monitoring of blood glucose * Unwillingness or inability to inject insulin and/or inject exenatide * Serum creatinine \>1.3 mg/dL in women or 1.4 in men * Retinopathy which has required photocoagulation for treatment * Major active systemic illness (e.g. neoplastic disorder, symptomatic ischemic heart disease, congestive heart failure) that might interfere with performing the study protocol * Clinically significant gastrointestinal disorder including prior gastric or intestinal surgery for weight-control * Ongoing use of any drug (e.g. narcotic analgesic, tricyclic antidepressant) that might alter gastric emptying * Use prednisone or other systemic glucocorticoid drug in the last 3 months * Use of any drug for weight-control (e.g. sibutramine, phentermine, orlistat) in the last 3 months * Use of any unproven investigational drug within the last 3 months