Hypothalamic Obesity following Craniopharyngioma Surgery: Results of a Pilot Trial of Combined Diazoxide and Metformin Therapy

Objective. To assess the effect of combined diazoxide-metformin therapy in obese adolescents treated for craniopharyngioma. Design. A prospective open-label 6-month pilot treatment trial in 9 obese subjects with craniopharyngioma. Diazoxide (2 mg/kg divided b.i.d., maximum 200 mg/day) and metformin (1000 mg b.i.d.). Whole body insulin sensitivity index (WBISI) and area-under-the-curve insulin (AUCins) were calculated. Results. Seven subjects completed: 4M/3F, mean ± SD age years, weight kg, BMI kg/m2, and BMI SDS . Two were withdrawn due to vomiting and peripheral edema. Of participants completing the study, the mean ± SD weight gain, BMI, and BMI SDS during the 6 months were reduced compared to the 6 months prestudy ( versus kg, ; versus kg/m2, ; versus , , resp.). AUCins correlated with weight loss (, ) and BMI decrease (, ). Conclusion. Combined diazoxide-metformin therapy was associated with reduced weight gain in patients with hypothalamic obesity. AUCins at study commencement predicted effectiveness of the treatment.