Metformin treatment for adolescent obesity has limited long-term benefits

Article Outline

• Question
• Design
• Setting
• Participants
• Intervention
• Outcomes
• Main Results
• Conclusions
• Commentary
• Copyright

Glaser Pediatric Research Network Obesity Study Group. Metformin extended release treatment of adolescent obesity: A 48-week randomized, double-blind, placebo-controlled trial with 48-week follow-up. Arch Pediatr Adolesc Med 2010;164:116-23.

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Question 

Among obese adolescents, does metformin extended release (XR) plus lifestyle intervention reduce body mass index (BMI) more than lifestyle intervention alone?

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Design 

Multicenter, randomized, double-blind, placebo-controlled clinical trial.

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Setting 

Six centers of the Glaser Pediatric Research Network, from October 2003 to August 2007.

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Participants 

Obese (BMI ≥ 95th percentile) adolescents (aged 13-18 years) were randomly assigned to the intervention (n=39) or placebo groups.

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Intervention 

Following a 1-month run-in period, subjects following a lifestyle intervention program were randomized 1:1 to 48 weeks' treatment with metformin XR, 2000mg once daily, or an identical placebo. Subjects were monitored for an additional 48 weeks.

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Outcomes 

Change in BMI, adjusted for site, sex, race, ethnicity, and age and metformin vs placebo.

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Main 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.

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Conclusions 

Metformin XR caused a small but statistically significant decrease in BMI when added to a lifestyle intervention program.

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Commentary 

This study makes an important contribution to the evidence on adolescent obesity management because it reports on long-term outcomes of metformin treatment, which has previously been studied only in trials of <6 months duration. Given the value of long-term weight maintenance over short-term reduction, the authors surprisingly underplay the results at week 100 (a primary outcome specified in the trial protocol), by which time the early beneficial effect of metformin on BMI disappears completely. Metformin may have a role in obesity management when used as an adjunct to effective lifestyle interventions, but this is difficult to establish from this study due to a relative lack of effect in the placebo arm treated with lifestyle intervention alone. More selective use of metformin may be appropriate in practice, for which studies that can identify groups of young people most likely to benefit from metformin therapy are needed. Large sample sizes will be necessary, as even in this highly motivated sample of adolescents, only a small proportion were available at final follow-up, raising the possibility of bias in results.