Differential effects of metformin and troglitazone on cardiovascular risk factors in patients with type 2 diabetes

OBJECTIVE — Traditional cardiovascular risk factors (CVRF) only partly explain the exces-sive risk of cardiovascular disease in patients with type 2 diabetes. There is now an increasing appreciation for many novel CVRF that occur largely as a result of insulin resistance and hyper-insulinemia. Therefore, we investigated whether diabetes medications that vary in their mech-anism of action and ability to reduce insulin resistance may differ in their effects on both traditional and novel CVRF. RESEARCH DESIGN AND METHODS — We compared the addition of metformin or troglitazone therapy on CVRF in 22 subjects with type 2 diabetes who remained in poor glycemic control (with HbA1c 8.5%) while taking glyburide 10 mg twice daily. Subjects were initially randomized to either metformin 850 mg once daily or troglitazone 200 mg once daily. Both medications were then titrated upward as needed to achieve fasting plasma glucose120 mg/dl. Measures of glucose control, insulin resistance, and CVRF (blood pressure, lipids, plasminogen activator inhibitor-1, C-reactive protein, fibrinogen, and small dense LDL) were assessed both before and after therapy. RESULTS — After 4 months of treatment, both metformin and troglitazone led to simila