The purpose of this study is to determine whether exenatide can cause weight loss in patients with a history of craniopharyngioma or other brain lesion.

Hypothalamic obesity occurs in up to 60% of patients with tumors in the hypothalamic region, most commonly craniopharyngiomas. Hypothalamic dysfunction can be due to tumor infiltration and as a consequence of surgery or radiation therapy. Survivors who develop obesity have greater morbidity and mortality than normal weight survivors. Prevention and treatment of obesity in this population is vital in order to decrease the morbidity and mortality from diabetes, stroke and myocardial infarction.

Exenatide (Byetta®) is a GLP-1 homologue that was FDA approved for treatment of type 2 diabetes in 2005. It also decreases the rate of gastric emptying and increases satiety and has been shown to cause weight loss in some people. Exenatide may improve insulin sensitivity and satiety in patients with hypothalamic obesity but without the risks of bariatric surgery. The investigators hypothesize that treatment with exenatide will lead to weight loss in patients with hypothalamic obesity.

Inclusion Criteria:

• Age 18 to 40 years old
• History of craniopharyngioma or other lesion in the hypothalamic region
• Greater than 6 months post-treatment, including chemotherapy, surgery or radiation
• BMI >30 mg/m2
• Females must be post-menopausal, surgically sterile or using effective birth control for at least 12 weeks

Exclusion Criteria:

• HgbA1C >7%
• Use of diabetes medications other than metformin in the past 12 weeks, including exenatide
• Use of weight loss drugs or initiation of a weight loss program in past 3 months
• Impaired renal function or history of kidney transplant
• History of gall stones (unless s/p cholecystectomy), pancreatitis or alcoholism
• Personal or family history of medullary carcinoma of the thyroid or MEN type 2
• History of gastroparesis or other gastric motility problems as exenatide decreases gastric motility
• History of allergic reaction to exenatide or other medication components
• Other significant comorbidities other than pituitary deficiencies
• Currently prescribed warfarin (exenatide may alter warfarin metabolism)
• Pregnant or lactating females
• History of severe hypoglycemia (BG <60 and requiring assistance from another person)

1 year