Background and objective: Childhood obesity is associated with reduced insulin sensitivity and increased risk for type 2 diabetes (T2D). The objective of the MOCA trial was to investigate the effect of metformin in severely obese children and adolescents.
Design and Methods: In a six month multi-centre randomized, double-blind placebo-controlled trial metformin (1.5 g daily) or placebo was given to children and adolescents (818 years) with insulin resistance and/or impaired glucose tolerance. Auxology, fasting insulin and glucose were performed at baseline, three and six months. The adiponectin: leptin (A/L) ratio was assessed.
Results: From 151 participants (placebo n=77, metformin n=74) with a mean age 13.7 (2.3) years and mean BMI-SDS +3.4 (0.5), 102 were (67.5%) female, 99 (65.6%) post-pubertal, 115 (76.2%) White British and 36 (23.8%) British Asian or Afro-Caribbean. In regression analysis (controlling for baseline values, sex, ethnicity and pubertal status) metformin had a greater treatment effect over placebo for BMI (−1.07 kg/m2: P=0.01, 95% CI 0.29 to 1.86) and BMI-SDS at 6 months (−0.1: P=0.01, 95% CI 0.02 to 0.19). The total number of participants with raised fasting insulin at 3 months decreased by 16% in the metformin group and increased by 14% in the placebo group. There was a mean reduction in fasting glucose in the metformin group (−0.03 mmol/l) at 3 months compared with a mean increase in the placebo group (+0.09 mmol/l), P=0.03 (95% CI 0.05 to 0.38). A/L ratio was improved at 3 months in the metformin group (+0.04) compared with a deterioration in the placebo group (−0.03), P=0.03 (95% CI −0.52 to −0.02), but this was not sustained at 6 months.
Conclusions: Metformin therapy has a beneficial treatment effect over placebo for BMI, BMI-SDS, fasting insulin, fasting glucose and A/L ratio at three months, with the changes in body composition sustained at six months.
Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.
Funding: No specific grant from any funding agency in the public, commercial or not-for-profit sector.