A review. Role of pioglitazone in reducing the cardiovascular risk in T2DM patients is discussed. In addition to lowering plasma glucose concentration, pioglitazone decreases insulin resistance (by 35-40%) in skeletal muscle, liver and adipocytes, decreases plasma triglyceride concentration, increases HDL cholesterol converts small dense atherogenic LDL particles to larger more buoyant ones, and reduces blood pressure, and also reduces plasma FFA, adipocytokines/other inflammatory markers/procoagulant factors, and increases plasma adiponectin, all of which would be expected to provide cardiovascular benefit. Thus, pioglitazone would be expected to provide addnl. cardiovascular benefits, independent of the reduction in plasma glucose concentration Lastly, in large clin. outcome studies, pioglitazone significantly lowered the incidence of 3-point MACE (non-fatal myocardial infarction, non-fatal stroke, CV death) in T2DM patients with established CVD.