Metformin extended release treatment of adolescent obesity: A 48-week randomized, double-blind, placebo-controlled trial with 48-week follow-up

Background: Metformin has been proffered as a therapy for adolescent obesity, although long-term controlled studies have not been reported. Objective: To test the hypothesis that 48 weeks of daily metformin hydrochloride extended release (XR) therapy will reduce body mass index (BMI) in obese adolescents, as compared with placebo. Design: Multicenter, randomized, double-blind, placebocontrolled clinical trial. Setting: The 6 centers of the Glaser Pediatric Research Network from October 2003 to August 2007. Participants: Obese (BMI≥95th percentile) adolescents (aged 13-18 years) were randomly assigned to the intervention (n=39) or placebo groups. Intervention: Following a 1-month run-in period, subjects following a lifestyle intervention program were randomized 1:1 to 48 weeks' treatment with metformin hydrochloride XR, 2000mgonce daily, or an identical placebo. Subjects were monitored for an additional 48 weeks. Main Outcome Measure: Change in BMI, adjusted for site, sex, race, ethnicity, and age and metformin vs placebo. Results: After 48 weeks, mean (SE) adjusted BMI increased 0.2 (0.5) in the placebo group and decreased 0.9 (0.5) in the metformin XR group (P=.03). This difference persisted for 12 to 24 weeks after cessation of treatment. No significant effects of metformin on body composition, abdominal fat, or insulin indices were observed. Conclusion: Metformin XR caused a small but statistically significant decrease in BMI when added to a lifestyle intervention program. Trial Registration: clinicaltrials.gov Identifiers: NCT00209482 and NCT00120146.