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 (2mg/kg divided b.i.d., maximum 200 mg/day) and metformin (1000 mg b.i.d.). Whole body insulin sensitivity index (WBISI) and areaunder-the-curve insulin (AUC(ins)) were calculated. Results. Seven subjects completed: 4M/3F, mean +/- SD age 15.4 +/- 2.9 years, weight 99.7 +/- 26.3 kg, BMI 35.5 +/- 5.6 kg/m(2), and BMI SDS 2.3 +/- 0.3. Two were withdrawn due to vomiting and peripheral edema.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 (+1.2 +/- 5.9 versus +9.5 +/- 2.7 kg, P =.004; - 0.3 +/- 2.3 versus +2.2 +/- 1.5 kg/m(2), P =.04; - 0.04 +/- 0.15 versus +0.11 +/- 0.08, P = .021, resp.). AUC(ins) correlated with weight loss (r = 0.82, P = .02) and BMI decrease (r = 0.96, P = .009). 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.