Metformin and placebo therapy both improve weight management and fasting insulin in obese insulin-resistant adolescents: a prospective, placebo-controlled, randomized study.

OBJECTIVE: To study whether metformin reduces obesity, homeostasis model assessment for insulin resistance index (HOMA-IR), and the metabolic syndrome (MtS) in obese European adolescents in addition to previous unsuccessful lifestyle intervention. DESIGN AND METHODS: After 6 months of multiprofessional lifestyle intervention, 70 out of 86 adolescents without improvement in body mass index (BMI) and HOMA-IR were randomized into either the placebo (n=34) or the metformin group (2×500 mg/day, n=36) in addition to ongoing lifestyle intervention for another 6 months.
RESULTS: Age was 13.8 years, BMI was 33.1 kg/m(2), 65% were female, and 89% were Caucasians. During lifestyle intervention alone, BMI and HOMA-IR deteriorated significantly. In the subsequent medication period, HOMA-IR and fasting insulin improved similarly in the placebo and metformin groups (HOMA-IR decreased 73 vs 54% respectively in metformin versus placebo; P=0.048), but BMI remained unchanged. The insulin sensitivity index, however, only improved in the metformin group. High fasting insulin is correlated with a subsequent BMI increase irrespective of the medication. MtS remained unchanged.
CONCLUSIONS: Obese European adolescents' insulin sensitivity improved without weight change during placebo or metformin intervention in addition to lifestyle intervention. Most differences did not reach statistical significance, probably due to improved compliance with lifestyle intervention as a placebo effect. In addition, the metformin dose may be too low.

RCT Entities:   Population Interventions Outcomes