Endocrine Abstracts (2012) 28 OC3.1

Metformin in obese children and adolescents (MOCA) trial

Deborah Kendall1, Rakesh Amin1, Timothy Barrett7, Paul Dimitri3, Fiona Ivison2, Mohammed Kibirige5, Verghese Mathew4, Krystyna Matyka6, Ann Mc Govern1, Lesley Tetlow2, Andy Vail1, Jerry Wales3, Neil Wright3, Peter Clayton1 & Catherine Hall1

1Department of Paediatric Endocrinology, Royal Manchester Children's Hospital, Manchester, United Kingdom; 2Department of Paediatric Biochemistry, Royal Manchester Children's Hospital, Manchester, United Kingdom; 3Department of Paediatric Endocrinology, Sheffield Children’s Hospital, Sheffield, United Kingdom; 4Department of Paediatrics, Hull Royal Infirmary, Hull, United Kingdom; 5Department of Paediatrics, James Cooke University Hospital, Middlesborough, United Kingdom; 6Department of Paediatrics, University Hospitals Coventry & Warwickshire NHS Trust, Coventry, United Kingdom; 7Paediatric Endocrinology, Birmingham Children’s Hospital, Birmingham, United Kingdom.

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 (8–18 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.