Randomized, controlled trial of metformin for obesity and insulin resistance in children and adolescents: improvement in body composition and fasting insulin.
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.
Srinivasan
Shubha
S
Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, Locked Bag 4001 Westmead, New South Wales 2145, Australia. shubhas@chw.edu.au
Ambler
Geoffrey R
GR
Baur
Louise A
LA
Garnett
Sarah P
SP
Tepsa
Mirijana
M
Yap
Fabian
F
Ward
Glenn M
GM
Cowell
Christopher T
CT
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
D007328:Insulin; D008687:Metformin