The present study was undertaken to investigate the effects of exenatide on body composition and circulating cardiovascular risk biomarkers. A total of 69 patients with type 2 diabetes and already treated with metformin were randomized to exenatide or insulin glargine and treated for 1 year. Patients treated with exenatide reduced significantly their body and trunkal fat mass by 11 and 13%, and improved their profile of circulating cardiovascular biomarkers. More specifically, exenatide increased total adiponectin by 12% and reduced high-sensitivity C-reactive protein by 61%. However, changes in biomarkers were not fully attributed to the observed changes in body fat mass. No significant changes in body composition or circulating biomarkers were found among patients treated with insulin glargine. These findings suggest that exenatide in addition to its glucose-lowering effect has beneficial effects on body fat mass and circulating cardiovasular risk markers.