The investigators are conducting a study that will investigate the possible mechanisms of weight loss associated with exenatide treatment and the metabolic characteristics of high responders (i.e. subjects who achieve greater than 5% weight loss) to exenatide treatment. The investigators will also examine the magnitude and duration of weight loss among a cohort of high responders over 52 weeks of treatment, and at 3 and 6 months following treatment.

Hypothesis:

The mechanisms of weight loss with exenatide are not fully understood, and weight loss responses to exenatide are highly variable, possibly reflecting distinct metabolic parameters. By identifying and following a group of obese women who lose greater than 5% body weight after short-term exenatide treatment, the investigators can gain insights into the possible mechanisms of weight loss and assess long-term weight loss with this pharmacotherapeutic intervention.

Primary Outcomes

The primary objectives of this study is:

- To investigate possible mechanisms and patterns of weight loss with exenatide treatment, especially among individuals who have robust early weight loss (greater than 5% weight loss in 12 weeks) with exenatide.

Secondary Outcomes

Our secondary objective is to identify metabolic characteristics that predict robust response to exenatide treatment.

Outcome measurements:

• Weight
• Body composition
• Resting energy expenditure (REE)
• Mixed meal test
• Thermic effect of food
• Serum metabolic parameters
• Hunger/Nausea/Satiety visual analog scales (VAS)
• Physical activity monitoring

Study Population

The study population will be generally healthy, non-diabetic women age 18-70 years with BMI 28-48 kg/m^2.

Inclusion Criteria:

• Females age 18-70
• BMI 28-48 kg/m^2
• Stable weight (greater than 3 kg weight gain or loss within 6 months of screening visit).
• Ability to give informed consent and follow verbal and written instructions in English.

Exclusion Criteria:

• Type 1 or type 2 diabetes mellitus diagnosed according to American Diabetes Association criteria
• Unstable heart disease as evidenced by ongoing angina
• Congestive heart failure
• Uncontrolled hypertension (BP greater than 170/100 mmHg on or off antihypertensive medication)
• Uncontrolled dyslipidemia (LDL greater than 200 or TG greater than 400 on or off lipid lowering medication)
• Tobacco, marijuana, cocaine, or intravenous drug use
• Shift workers (night shift or alternating day/night shifts)
• Gastroparesis
• Inflammatory bowel disease or irritable bowel syndrome
• Malignancy treated with chemotherapy within the past 3 years
• History of pancreatitis
• Depression requiring hospitalization or diagnosis of psychosis
• Renal insufficiency (eGFR less than 50)
• Transaminases greater than 2 times above the normal range
• Pregnancy within 6 months of the screening visit
• Lactation
• Failure to use medically approved contraceptive methods (monophasic oral contraception, intra uterine device, surgical sterilization or 2 combined barrier methods)
• History of an eating disorder (anorexia, bulimia or laxative abuse)
• Treatment with FDA-approved or over-the-counter weight loss medication within 6 months, with the exception of Xenical if there was no weight loss
• History of gastric bypass surgery or gastric stapling
• Biochemical evidence of hyper or hypothyroidism, or new diagnosis of hypo or hyperthyroidism within 3 months of screening visit
• Previous treatment with exenatide
• Discretion of the PI

Analysis population is the same as baseline population

Entire study duration, up to 1 year

Adverse events and serious adverse events are defined according to clinicaltrials.gov definition. Adverse event information was collected at each study visit, in person.