Metformin in obese children and adolescents: the MOCA trial.

CONTEXT Childhood obesity is increasingly associated with type 2 diabetes (T2D). Metformin reduces the risk for T2D in adult obese nondiabetic patients, but the evidence in obese children and young people is inconclusive. OBJECTIVE The objective of the study was to assess the effect of metformin on body mass index sd score (BMI-SDS), metabolic risk factors, and adipokines. DESIGN This was a prospective, randomized, double-blind, placebo-controlled trial. SETTING The study was conducted at six pediatric endocrine centers in the United Kingdom. PARTICIPANTS One hundred fifty-one obese children and young people with hyperinsulinemia and/or impaired fasting glucose or impaired glucose tolerance (metformin: 74, placebo: 77). The study was comprised of 67.5% females, 65.6% postpubertal individuals, and 23.8% British Asian or Afro-Caribbean participants. The age range was 8-18 yr, the mean age was 13.7 (SD 2.3) yr, and the mean BMI-SDS was +3.4 (SD 0.5). INTERVENTIONS The intervention included metformin 1 g in the morning and 500 mg in the evening vs. placebo for 6 months. MAIN OUTCOME MEASURE The main outcome measure was a reduction in BMI-SDS at 6 months. Secondary outcomes included insulin and glucose levels from oral glucose tolerance tests, alanine aminotransferase (ALT), and adiponectin to leptin ratio (ALR) at 3 and 6 months. RESULTS Metformin was associated with a significant reduction in BMI-SDS compared with placebo at 6 months [mean difference -0.1 SD (95% confidence interval -0.18 to -0.02), P = 0.02]. Significant improvements at 3 months were found in the metformin group: fasting glucose, -0.16 mmol/liter (-0.31 to -0.00), P = 0.047; ALT, 19% (5-36%), P = 0.008; and ALR, 32% (4-67%), P = 0.02. CONCLUSIONS Metformin therapy has a beneficial treatment effect over placebo for BMI-SDS, fasting glucose, ALT, and ALR ratio at 3 months, with changes in BMI-SDS sustained at 6 months.