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.