The insulin resistance syndrome is composed of risk factors for cardiovascular disease, including insulin resistance with hyperinsulinemia, atherogenic dyslipidemia, hypertension, abdominal obesity, and impaired hemostasis. Patients with type 2 diabetes frequently manifest multiple risk factors for cardiovascular morbidity and mortality. Management of the insulin resistance syndrome often includes antihypertensive, lipid-lowering, and antihyperglycemic agents. Because thiazolidinediones (TZDs) directly improve insulin resistance, early use may provide substantial benefits to patients with type 2 diabetes. TZDs reduce plasma glucose and insulin concentrations, promote relocation of body fat, and have anti-inflammatory effects on the vascular endothelium. Combination oral hypoglycemic therapy may be ideal for maintaining adequate glycemic control in patients with type 2 diabetes. The combination of a TZD and a biguanide, which improves insulin sensitivity and lowers blood glucose through different pathways, offers significant benefits and may help prevent or delay prevent complications associated with type 2 diabetes.