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

European journal of endocrinology / European Federation of Endocrine Societies 2010 Jul 16; In press

Wiegand S, L'allemand D, Huebel H, Krude H, Buermann M, Martus P, Grüters A, Holl R

S Wiegand, Pediatric Endocrinology and Diabetology, Charité; Universitätsmedizin Berlin, Berlin, Germany.

Objective: To study whether metformin reduces obesity, insulin resistance (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 metformin group (2x500mg/d, n=36) in addition to ongoing lifestyle intervention for another 6 months. Results: Age was 13.8 years, BMI 33.1 kg/m2, 65% female, 89% 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 in 73% versus 54% respectively; 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 medication. MtS remained unchanged. Conclusions: European adolescents' insulin sensitivity improved without weight change during placebo or metformin 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.

Keywords: Metformin insulin