A Pilot Study of Effects of Exenatide on Body Weight in Non-Diabetic, Obese Patients

• Change in Body Mass Index (BMI) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Change in BMI from baseline after 24 weeks of treatment (i.e., BMI at week 24 minus BMI at week 0)
• Change in Waist-to-hip Ratio [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Waist-to-hip ratio at week 24 compared to waist-to-hip ratio at week 0 (i.e., waist-to-hip ratio at week 24 minus waist-to-hip ratio at week 0). Waist-to-hip ratio equals waist circumference at given time point divided by hip circumference at given timepoint.
• Percentage of Patients Experiencing >=5% Weight Loss [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Percentage of exenatide and placebo treated patients experiencing >=5% weight loss after 24 weeks of treatment (i.e., [weight at week 0 minus weight at week 24] divided by weight at week 0 times 100% >=5%)
• 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 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)
• Ratio of Endpoint (LOCF) to Baseline for Fasting Triglycerides (Logarithmically Transformed) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Ratio of triglycerides at week 24 compared to triglycerides at week 0 (i.e., triglycerides at week 24 divided by triglycerides 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 following 24 weeks of treatment (i.e., LDL cholesterol at week 24 minus LDL cholesterol at week 0)
• Change in Fasting Serum Glucose [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Change in fasting serum glucose from baseline following 24 weeks of treatment (i.e., fasting serum glucose at week 24 minus fasting serum glucose at week 0)
• Change in Serum Glucose AUC Levels Following Oral Glucose Tolerance Test (OGTT) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Change in serum glucose AUC following OGTT (week 24 compared to week 0) (i.e., serum glucose AUC at week 24 minus serum glucose AUC at week 0)
• Ratio of Endpoint (LOCF) to Baseline for Homeostatic Model Assessment-Beta Cell (HOMA-B) (Logarithmically Transformed) [ 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.
• Ratio of Endpoint (LOCF) to Baseline for Homeostatic Model Assessment-Insulin Sensitivity (HOMA-S) (Logarithmically Transformed) [ 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.
• Incidence of Patients That Demonstrate Overt Signs of Diabetes Mellitus Diagnosis [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Number of patients in each treatment group that demonstrate overt signs of diabetes mellitus diagnosis by week 24
• Incidence of Patients That Demonstrate Normalization of Impaired Fasting Glucose (IFG) and/or Impaired Glucose Tolerance (IGT) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Number of patients in each treatment group that demonstrate normalization of IFG and/or IGT by week 24
• Change in High Sensitivity C-reactive Protein (hsCRP) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Change in hsCRP levels from baseline following 24 weeks of treatment (i.e., hsCRP at week 24 minus hsCRP at week 0)
• Change in Glycosylated Hemoglobin (HbA1c) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  Change in HbA1c from baseline following 24 weeks of treatment (i.e., HbA1c at week 24 minus HbA1c at week 0)

• To compare the placebo and exenatide treatment groups on the change in: *Body Mass Index (BMI) *Waist circumference and hip circumference *Proportion of patients experiencing >=5% weight loss *Various pharmacodynamic measurements [ Time Frame: 24 weeks ]
• *Beta cell function and insulin sensitivity *Proportion of patients that demonstrate overt signs of diabetes diagnosis or normalization of impaired fasting glucose and/or impaired glucose tolerance *Safety and tolerability *Health outcome measures [ Time Frame: 24 weeks ]

This is a multicenter study designed to compare the effect of exenatide plus a lifestyle modification plan versus placebo plus a lifestyle modification plan on weight loss in non-diabetic, obese subjects.

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

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

Inclusion Criteria:

• Have a Body Mass Index (BMI) >= 30kg/m^2

Exclusion Criteria:

• Have ever participated in this study previously, or any other study using exenatide (AC2993/LY2148568) or GLP-1 analogs
• Have participated in an interventional medical, surgical, or pharmaceutical study (a study in which an experimental, drug, medical, or surgical treatment was given) within 30 days of study start (this criterion includes drugs that have not received regulatory approval for any indication at the time of study entry)
• Diagnosis of diabetes mellitus (other than gestational diabetes), or previous use of anti-diabetic medications for > 3 months
• Have had a change in prescribed lipid-lowering or blood pressure agents within 4 weeks of screening
• Used drugs for weight loss (e.g., Xenical [orlistat], Meridia [sibutramine], Acutrim [phenylpropanolamine], Accomplia [rimonabant], Alli [low-dose orlistat], or other similar over-the-counter weight loss remedies or medications) within 3 months of screening
• Are actively participating in, or have participated in a formal weight loss program within the last 3 months
• Have a history of chronic use of drugs that directly affect gastrointestinal motility, including, but not limited to Reglan (metoclopramide) and chronic macrolide antibiotics
• Have been treated with any anti-diabetic medications within 3 months of screening
• Are receiving chronic (lasting longer than 2 weeks) systemic glucocorticoid therapy or have received such therapy within the 4 weeks immediately prior to study start
• Have had bariatric surgery
• Have had an organ transplant