While metformin is commonly used as a primary or adjunctive treatment in obese, nondiabetic adolescents, there are limited short-term data to support this therapy. This 48-week randomized, double-blind, placebo-controlled trial of extended-release (XR) metformin therapy in nondiabetic obese adolescents was conducted in 5 clinical sites in the United States. Metformin XR had a small, but statistically significant, impact on body mass index during the initial 52 weeks of the study; this difference disappeared by 24 weeks after cessation of the drug. There were no significant effects on central adiposity, insulin indices, or lipids during metformin therapy. Longer-term studies will be needed to define the effects of metformin treatment on obesity-related disease risk in this population.