title: Randomized, controlled trial of metformin for obesity and insulin resistance in children and adolescents: improvement in body composition and fasting insulin.
abstract: BACKGROUND
  Metformin therapy for adults and children with type 2 diabetes is well established. However, its role in the treatment of insulin resistance and obesity in children and adolescents is less clearly defined.
  
  
  OBJECTIVE
  We assessed the effect of metformin on body composition and insulin sensitivity in pediatric subjects with exogenous obesity.
  
  
  METHODS
  Patients referred to a pediatric endocrine clinic were enrolled in a randomized, double-blind, crossover trial.
  
  
  METHODS
  Twenty-eight patients (13 males) aged 9-18 yr participated in the study.
  
  
  METHODS
  Patients received metformin (1 g twice daily) and placebo for 6 months, each with a 2-wk washout period.
  
  
  METHODS
  Body composition (anthropometry, dual-energy x-ray absorptiometry, and abdominal magnetic resonance imaging), and insulin sensitivity (Si; minimal model, fasting insulin and glucose) were measured at baseline and 6 and 12 months.
  
  
  RESULTS
  Mean age of subjects at baseline was 12.5 +/- 2.2 yr, median body mass index z-score 2.54 (range, 1.93-2.85). Metformin had a greater treatment effect over placebo for weight (-4.35 kg, P = 0.02), body mass index (-1.26 kg/m(2), P = 0.002), waist circumference (-2.8 cm, P = 0.003), sc abdominal adipose tissue (-52.5 cm(2), P = 0.002), and fasting insulin (-2.2 mU/liter, P = 0.011). Si improved in 45% of subjects while on metformin and 27% of subjects while on placebo (P = 0.21).
  
  
  CONCLUSIONS
  Metformin therapy for obese insulin-resistant pediatric patients results in significant improvement in body composition and fasting insulin. Although improvement in Si was noted in many individuals, Si was a less useful parameter for analysis of group data, possibly because of effects of variable compliance and changing Si during puberty.
authors.affiliation: Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, Locked Bag 4001 Westmead, New South Wales 2145, Australia. shubhas@chw.edu.au
authors.forename: Shubha
authors.initials: S
authors.lastname: Srinivasan
authors.forename: Geoffrey R
authors.initials: GR
authors.lastname: Ambler
authors.forename: Louise A
authors.initials: LA
authors.lastname: Baur
authors.forename: Sarah P
authors.initials: SP
authors.lastname: Garnett
authors.forename: Mirijana
authors.initials: M
authors.lastname: Tepsa
authors.forename: Fabian
authors.initials: F
authors.lastname: Yap
authors.forename: Glenn M
authors.initials: GM
authors.lastname: Ward
authors.forename: Christopher T
authors.initials: CT
authors.lastname: Cowell
mesh_terms: D000293:Adolescent; D001823:Body Composition / Q000187:drug effects*; D015992:Body Mass Index; D002648:Child; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005215:Fasting / Q000097:blood*; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D008297:Male; D008687:Metformin / Q000009:adverse effects / Q000627:therapeutic use*; D009765:Obesity / Q000188:drug therapy*; D010349:Patient Compliance
chemical_list: D007328:Insulin; D008687:Metformin