Weight Loss With Exenatide Treatment
Condition: Obesity
MeSH terms: Weight Loss
Intervention: Exenatide; Placebo; Dietary counseling
Intervention description: Subjects will inject 5mcg of exenatide subcutaneously 15 minutes before the morning and evening meal for the first 2 weeks of the study. At study week 2, subjects will increase to 10mcg twice daily for the remainder of the study.; Subjects will inject 5mcg of identically dispensed placebo subcutaneously 15 minutes before the morning and evening meal for the first 2 weeks of the study. At study week 2, subjects will increase to 10mcg twice daily for the remainder of the study.; All subjects will also receive individualized dietary counseling. Subjects in the placebo group will be counseled to follow a hypocaloric diet.
Intervention MeSH terms: Exenatide
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Enrollment: 249.0
Sex: Female
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Obesity; Overweight; Exenatide; Diet; Women

Summary:

      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.
    

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