Effects of Metformin and Rosiglitazone on Peripheral Insulin Resistance and β-Cell Function in Obesity: a Double-blind, Randomized, Controlled Study

Metformin and rosiglitazone combination therapy is known to improve insulin resistance and postpone diabetes mellitus development in subjects with impaired glucose tolerance. This double-blind, randomized, controlled study assessed this combination therapy for preventing type 2 diabetes in obese subjects with hyperinsulinaemia. Subjects received metformin (500 mg three times daily, orally) plus either rosiglitazone (4 mg once daily, orally; n = 94) or placebo (n 95) and were followed for 6 months. Blood pressure, body fat, body mass index (BMI), lipid and insulin levels were recorded pre- and post-treatment. Metformin plus rosiglitazone significantly decreased blood pressure, lipids, BMI, and fasting and postmeal insulin levels. Metformin plus placebo led to a significant decrease in blood pressure, BMI and lipid levels, but fasting and postmeal insulin levels were unchanged. Adverse events were similar between the two groups. The metformin and rosiglitazone combination increased insulin sensitivity and beta-cell function recovered. This approach may represent a therapeutic option for preventing development of type 2 diabetes in obese subjects with hyperinsulinaemia.