Combination Therapy with Metformin and Fenofibrate for Insulin Resistance in Obesity

This randomized controlled study investigated metformin and fenofibrate, compared with metformin alone, for the treatment of peripheral insulin resistance in patients with simple obesity with hyperinsulinaemia but not diabetes. Participants were randomized to receive metformin (500 mg orally three times daily) plus either fenofibrate (200 mg orally once daily; n = 44) or placebo (n = 43) for 6 months. Blood pressure, free fatty acids (FFA), body mass index (BMI), lipid and insulin levels were recorded pre- and post-treatment. beta-Cell function and insulin resistance were measured by the homeostasis model assessment for insulin resistance (HOMA-IR) index. Both groups showed significant decreases in blood pressure, FFA, BMI and HOMA-IR relative to baseline. In addition, combined metformin and fenofibrate therapy showed significantly decreased fasting and postmeal insulin levels relative to baseline and relative to the placebo group. Both treatments were well tolerated. Metformin and fenofibrate can increase insulin sensitivity and recover beta-cell function in patients with simple obesity accompanied by insulin resistance.