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 (-4.35 kg, P = 0.02), body mass index (-1.26 kg/m(2), P = 0.002), waist circumference (-2.8 cm, 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.