In order to compare the ability of rosiglitazone and metformin to improve markers of glucose-insulin homeostasis, Brunami et al. administered metformin (850 mg twice daily) or rosiglitazone (4 mg twice daily) for a 6 month period to, respectively, 9 and 13 obese, non-diabetic subjects undergoing a diet-induced weight loss program. Both drugs induced similar weight loss and reduction in fat mass. Rosiglitazone improved fasting glucose and insulin levels as well as β-cell function as estimated by the homeostatic model of insulin resistance. However, no significant improvements were reported for patients treated with metformin. Study results suggest that a diet-induced weight loss program might prevent rosiglitazone-induced weight gain and possibly decrease body weight. The authors acknowledged that a larger, randomized study is needed to validate the results.