Metformin in Obese Children and Adolescents: The MOCA Trial.

Kendall D, Vail A, Amin R, Barrett T, Dimitri P, Ivison F, Kibirige M, Mathew V, Matyka K, McGovern A, Stirling H, Tetlow L, Wales J, Wright N, Clayton P, Hall C.

Source

Royal Manchester Children's Hospital (D.K., R.A., F.I., A.M., L.T., P.C., C.H.), Manchester M13 9WL, United Kingdom; Birmingham Children's Hospital (T.B.), Birmingham, B4 6NH, United Kingdom; Sheffield Children's Hospital (P.D., J.W., N.W.), Western Bank, Sheffield S10 2TH, United Kingdom; The University of Sheffield (P.D., J.W., N.W.), Western Bank, Sheffield S10 2TN, United Kingdom; The James Cook University Hospital (M.K.), Middlesbrough, Cleveland TS4 3BW, United Kingdom; Hull Royal Infirmary (V.M.), Hull, East Yorkshire HU3 2JZ, United Kingdom; University Hospital Coventry and Warwickshire National Health Service Trust (K.M., H.S.), Coventry CV2 2DX, United Kingdom; Centre for Biostatistics (A.V.), University of Manchester, Manchester Academic Health Science Centre, Salford Royal National Health Service Foundation Trust, Salford M6 8HD, United Kingdom; and Manchester Academic Health Sciences Centre (P.C.), University of Manchester, Manchester M13 9PL, United Kingdom.

Abstract

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.

TimAllenMDJD

Sunday, November 25, 2012