Metformin may aid weight loss in overweight teenage girls

Article Outline

• Love-Osborne K, Sheeder J, Zeitler P. Addition of metformin to a lifestyle modification program in adolescents with insulin resistance. J Pediatr 2008;152:817-22
• References
• Copyright

Back to Article Outline

Love-Osborne K, Sheeder J, Zeitler P. Addition of metformin to a lifestyle modification program in adolescents with insulin resistance. J Pediatr 2008;152:817-22 

Question Among obese adolescents, does metformin, when added to a program of personal goal setting, improve weight loss and clinical status compared with placebo?

Design Randomized, double-blind, placebo controlled trial.

Setting Children's Hospital, Denver, CO.

Participants Eighty-five adolescents (mean age 15.7 years, mean body mass index (BMI) of 39.7 kg/m²) with insulin resistance. A total of 58% of the children were Hispanic, and 34% were African-American.

Intervention Participants were randomized to receive metformin (70%) or placebo (30%), along with monthly goal setting for diet and exercise modification.

Outcomes Anthropometric measures, fasting blood analysis, and glucose tolerance tests at 6 months.

Main Results A total of 76% of participants completed the study. There were no group differences between metformin and placebo in weight loss or measures of glucose metabolism. However, among females taking metformin, there was a significant decrease in BMI not seen in the placebo group (loss of 0.40 kg/m² ± 1.60 with metformin compared with a gain of 1.04 kg/m² ± 1.19). Furthermore, metformin adherence, when accompanied by lifestyle change, was a predictor of BMI decrease of 5% or more: 6 of 10 subjects who adhered to metformin and decreased portion size decreased BMI by >5%. Goal setting alone did not result in significant weight loss.

Conclusions In this group of predominately minority adolescents, monthly goal setting alone did not lead to weight loss. Although the addition of metformin had no effect on weight loss overall, the agent did significantly increase weight loss among females, and weight loss was predicted by degree of metformin adherence. However, weight loss was only found in those participants also reporting lifestyle change, particularly a decrease in portion sizes. These results suggest that metformin may be a useful agent to promote short-term weight loss among girls making modest lifestyle changes.

Commentary “Metformin is not a weight-loss drug,” is the caveat I have heard myself say many times as I prescribe it to my obese adolescent females with polycystic ovarian syndrome. For that population, sometimes weight loss is a welcome side effect. This new study directly evaluates the role of metformin, in combination with lifestyle modification, as a tool for weight loss in obese teens. This well-designed RCT included those at highest risk for comorbidities: Hispanics and African-Americans. The rate of completion (76%) was similar to another RCT examining effect of sibutramine for overweight adults (78.6%),¹ and slightly lower than a study evaluating effect of sibutramine in overweight adolescents (90.2%).² This occurred despite a 2:1 randomization protocol, done presumably to see positive changes in a higher proportion, and encourage study completion. In absolute terms, metformin did not statistically affect change in BMI or in metabolic parameters over the 6 month time frame. However, metformin-treated subjects had significantly higher chances of decreasing BMI by at least 5%. Also, there was a linear correlation between metformin adherence and weight loss, suggesting the biologic plausibility of a weight loss effect of this medication. Use of the extended-release preparation, rapidly titrated to a higher dose, may have led to more significant results for 2 reasons: (1) better adherence and (2) increased early success, encouraging better adherence to the goal-setting part of the study. Making these changes, as well as prolonging the study, have the potential to show significant impact of a medication that has a good benefit-to-risk ratio. Guidelines for treatment of obesity in children at this time remain focused on lifestyle changes,³ but this study represents an important step toward adding tools for those at highest risk.

Back to Article Outline

References 

1. Wadden TA, Berkowitz RI, Womble LG, Sarwer DB, Phelan S, Cato RK, et al. Randomized trial of lifestyle modification and pharmacotherapy for obesity. N Engl J Med. 2005;353:2111–2120
   • View In Article
   • CrossRef
2. Berkowitz RI, Wadden TA, Tershakovec AM, Cronquist JL. Behavior therapy and sibutramine for the treatment of adolescent obesity: A randomized controlled trial. JAMA. 2003;289:1805–1812
   • View In Article
   • MEDLINE
   • CrossRef
3. Dietz WH, Robinson TN. Overweight children and adolescents. N Engl J Med. 2005;352:2100–2109
   • View In Article
   • CrossRef