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 (AUC(ins)) were calculated. Results. Seven subjects completed: 4M/3F, mean ± SD age [Image: see text] years, weight [Image: see text] kg, BMI [Image: see text] kg/m(2), and BMI SDS [Image: see text]. Two were withdrawn due to vomiting and peripheral edema.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 ([Image: see text] versus [Image: see text] kg, [Image: see text]; [Image: see text] versus [Image: see text] kg/m(2), [Image: see text]; [Image: see text] versus [Image: see text], [Image: see text], resp.). AUC(ins) correlated with weight loss ([Image: see text], [Image: see text]) and BMI decrease ([Image: see text], [Image: see text]). Conclusion. Combined diazoxide-metformin therapy was associated with reduced weight gain in patients with hypothalamic obesity. AUC(ins) at study commencement predicted effectiveness of the treatment.