Efficacy and Safety of Exenatide in the Treatment of Hypothalamic Obesity After Craniopharyngioma Therapy

The development of glucagon-like peptide-1 (GLP-1) analogues might be a solution since native GLP-1 suppresses appetite and energy intake in both normal weight and obese individuals as well as in people with type 2 diabetes and delays gastric emptying. The underlying mechanisms that mediate the effects of weight involve not only central regions like the hypothalamus and the solitary tractus nucleus and area postrema but also peripheral regions as the gastrointestinal tract. These extra hypothalamic effects are of particular interest in the cases of obesity due to hypothalamic lesions.

Exenatide is a glucagon-like peptide-1 (GLP-1) analogue with a high structural homology to human GLP-1, a gut derived incretin hormone. Since exenatide causes a dose-dependent weight loss, decreasing concentration of glycosylated haemoglobin as well as improving ß-cell function and systolic blood pressure, it could be an attractive treatment for both type 2 diabetes and obesity. In a double-blind placebo-controlled 24-week trial, it has been recently shown that non diabetic obese patients maintained on exenatide 10µg x 2/j lost significantly more weight than did those on placebo (5.1 kg versus 1.6).

Inclusion criteria

• They are between 18 and 75 yrs.
• They had been diagnosed with a craniopharyngioma treated by surgery and/or irradiation without sign of recurrence.
• They have a BMI upper than 30kg/m² with intractable weight gain following therapy for craniopharyngioma.
• They demonstrate at least one other endocrinopathy, as a marker of hypothalamic damage.
• All pituitary deficiencies are correctly treated.
• They gave their written, informed consent before the beginning of the study.

Exclusion criteria

• They have type 1 diabetes.
• They have type 2 diabetes treated with insulin.
• Acidocetosis.
• Bariatric surgery
• Previous personal history of thyroid or pancreatic cancer.
• Hypercalcitoninemia.
• They have been previously treated by GLP1 analogs.
• Hypertriglyceridemia upper than 5g/l
• They had previously demonstrated voluntary weight loss during the three previous months.
• They are under the age of 18 years or over the age of 65 yrs.
• They are maintained on medical treatment against obesity.
• They are receiving supraphysiologic hydrocortisone therapy (upper than 30 mg/jour).
• Their GH status change during the course of the study.
• Exenatide is contraindicated.
• Psychological and/or medical problems that would create difficulties for the patient to comply with the study protocol are present.