Although numerous clinical trials have evaluated the body weight change achieved using diabetes medications alone or in combinations, the composition of body weight change in these clinical trials has rarely been assessed. We aimed to evaluate the effects of gliclazide, metformin, and acarbose monotherapy on body composition, fat distribution, and other cardiometabolic risk factors in patients with newly diagnosed type 2 diabetes. A total of 86 patients with newly diagnosed type 2 diabetes mellitus were randomly assigned to receive gliclazide, metformin, or acarbose for 6 months. Dual-energy x-ray absorptiometry; abdominal computed tomography scans; and measurements of adiponectin, leptin, and lipid levels were performed before and after 6-month monodrug therapy. Blood glucose and glycosylated hemoglobin levels significantly improved after 6 months of monodrug therapy. During the 6 months of use of the 3 antidiabetes medications, the majority of participants experienced fat mass loss and lean mass gain. Metformin monotherapy in patients with newly diagnosed type 2 diabetes led to a significant decrease in percent body fat (P = 0.029) and body fat mass (P = 0.038). Levels of serum total cholesterol (P = 0.004), triglycerides (P = 0.014), and adiponectin (P = 0.001) took a favorable turn after metformin treatment. The 3 antidiabetes medications caused no significant change in abdominal fat distribution, waist circumstance, and blood pressure during the 6 months. Our results suggest metformin therapy in patients with newly diagnosed type 2 diabetes can improve cardiometabolic risk markers. Moreover, body composition change induced by gliclazide and acarbose was not likely to be simple fat deposition.