The Effect of Exenatide on Weight and Hunger in Obese, Healthy Women
The Effect of Exenatide on Weight and Hunger in Obese, Healthy Women
This study will look at the effect of exenatide, a drug which has been approved for the
 treatment of type 2 diabetes, on body weight, appetite and energy expenditure among
 moderately obese women without diabetes.

 The study is 35 weeks long and includes 19 outpatient visits. Participants will receive
 exenatide for 16 weeks and placebo for 16 weeks with a 3 week rest period in between. Neither
 participants nor investigators will know whether exenatide or placebo is being administered.
 Participants will be started randomly on either exenatide or placebo.

 Our hypothesis is that treatment with exenatide will curb appetite and lead to weight loss
 and may lead to changes in energy expenditure.
This study will examine the effect of exenatide on body weight, energy expenditure, satiety,
 sleep, and metabolic parameters in healthy, moderately obese women (BMI 28-35 kg/m2). We will
 look at 2 populations of women, one with normal glucose metabolism and one with impaired
 glucose homeostasis (IGH)--either impaired fasting glucose (IFG, fasting glucose 101-125
 mg/dL) or impaired glucose tolerance (IGT, glucose 140-199 mg/dL 2h after a 75g oral glucose
 load). This is a randomized, double blind, crossover study with two 16-week treatment periods
 separated by a 3-week washout period. There are 19 study visits over 35 weeks.

 The goals of this study are 1) to examine the effect of exenatide on body weight and
 dysglycemia in populations in which this medication has not been studied, namely obese women
 with and without IGH and 2) to investigate possible mechanisms of weight loss through
 measurements of energy expenditure, hunger, satiety, nausea, and sleep.

 The primary outcome of this study is weight loss. We will calculate absolute and relative
 change in body weight from baseline to week 16 (the first treatment period) and from week 19
 to week 35 (the second treatment period). Body weight will be measured at every study visit
 which will also allow us to assess the absolute and relative change from baseline throughout
 the entire study.
Inclusion Criteria:

 1. Females aged 25-60

 2. BMI 28-35 kg/m2

 3. No known diagnosis of diabetes

 4. No known diagnosis of coronary heart disease

 5. Self-described sedentary lifestyle with minimal regular cardiovascular exercise (no
 more than 1 hour per week)

 6. Stable weight (variation < 3 kg within 6 months of screening visit)

 7. Ability to give informed consent

 8. Ability to follow verbal and written instructions

 9. Use of medically approved form of contraception (monophasic oral contraception, intra
 uterine device, surgical sterilization or 2 combined barrier methods)

 10. Nonsmoker (tobacco, marijuana)

 11. Outpatient visits every 2 weeks throughout the study period are required. While most
 of these visits are short (15 minutes)ability to commute to the performance site in
 Boston, on a regular basis, is necessary.

 Exclusion Criteria:

 1. Type 1 or type 2 diabetes mellitus diagnosed according to American Diabetes
 Association criteria

 2. Coronary heart disease (history of myocardial infarction or unstable angina pectoris)

 3. Uncontrolled hypertension hypertension (BP > 150/90 mmHg on or off antihypertensive
 medication)

 4. Uncontrolled dyslipidemia (LDL > 200 or TG > 400 on or off lipid lowering medication)

 5. Tobacco, marijuana or intravenous drug use

 6. Shift workers (night shift or alternating day/night shifts)

 7. Recent weight loss (> 3 kg within 4 months of the screening visit)

 8. Gastroparesis

 9. Inflammatory bowel disease

 10. Malignancy treated with chemotherapy within the past 3 years

 11. History of pancreatitis

 12. Depression requiring hospitalization or diagnosis of psychosis

 13. Renal insufficiency (creatinine clearance < 50 ml/min)

 14. Transaminases > 2x above the normal range

 15. Pregnancy within 6 months of the screening visit

 16. Breastfeeding

 17. Failure to use medically approved contraceptive methods

 18. History of an eating disorder (anorexia, bulimia or laxative abuse)

 19. History of surgery for the treatment of obesity (gastric banding, gastric bypass,
 gastric stapling)

 20. New diagnosis of hypo or hyperthyroidism within 1 year of screening visit

 21. Previous participation in a clinical study with exenatide

 22. Presence or history of allergic reaction to multiple drugs