Weight Loss With Exenatide Treatment

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.

Eligibility Criteria:
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