Randomized, controlled trial of metformin for obesity and insulin resistance in children and adolescents: Improvement in body composition and fasting insulin

Context: Metformin therapy for adults and children with type 2 diabetes is well established. However, its role in the treatment of insulin resistance and obesity in children and adolescents is less clearly defined. Objective: We assessed the effect of metformin on body composition and insulin sensitivity in pediatric subjects with exogenous obesity. Design and Setting: Patients referred to a pediatric endocrine clinic were enrolled in a randomized, double-blind, crossover trial. Patients: Twenty-eight patients (13 males) aged 9-18 yr participated in the study. Intervention: Patients received metformin (1 g twice daily) and placebo for 6 months, each with a 2-wk washout period. Main Outcome Measures: Body composition (anthropometry, dual-energy x-ray absorptiometry, and abdominal magnetic resonance imaging), and insulin sensitivity (Si; minimal model, fasting insulin and glucose) were measured at baseline and 6 and 12 months. Results: Mean age of subjects at baseline was 12.5 +/- 2.2 yr, median body mass index z-score 2.54 ( range, 1.93-2.85). Metformin had a greater treatment effect over placebo for weight (-4.35kg, P = 0.02), body mass index (-1.26 kg/m(2), P = 0.002), waist circumference (-2.8cm, P = 0.003), sc abdominal adipose tissue (-52.5 cm(2), P = 0.002), and fasting insulin (-2.2 mU/liter, P = 0.011). Si improved in 45% of subjects while on metformin and 27% of subjects while on placebo (P = 0.21). Conclusions: Metformin therapy for obese insulin-resistant pediatric patients results in significant improvement in body composition and fasting insulin. Although improvement in Si was noted in many individuals, Si was a less useful parameter for analysis of group data, possibly because of effects of variable compliance and changing Si during puberty.