Thiazolidinediones: antidiabetic drugs with cardiovascular effects.

cardiovascular morbidity and mortality at least four times higher compared to patients without diabetes. Moreover, it is well established nowadays that the cardiovascular risk of diabetic patients without a history of a prior myocardial infarction is similar to the risk of nondiabetic patients who have already had one. Hence, the reduction of cardiovascular risk in type 2 diabetic patients using antidiabetic medication is of great importance. In the last few years thiazolidinediones (glitazones), a new class of antidiabetic drugs, have been developed. These drugs are potent and highly selective agonists for peroxisome proliferator-activated receptors (PPAR Á), directly improving insulin sensitivity at the sites of insulin action in type 2 diabetes patients. Furthermore, thiazolidinediones seem to have pleiotropic vascular protective effects, as they appear to improve diabetic dyslipidaemia, hypertension and abnormalities of the coagulation-fibrinolysis system, thus reducing the overall cardiovascular risk in patients with the metabolic syndrome. There is substantial evidence to suggest that glitazones not only ameliorate insulin resistance at the level of adipocytes, skeletal muscles and liver, but also may play a beneficial role in other underlying pathophysiological mechanisms of vascular impairment, such as atherosclerosis and inflammation. Troglitazone, which became available in practice in 1997, was the first agent of this class, but it was subsequently withdrawn from the market in 2000 because of hepatotoxicity. The two currently available members of the thiazolidinedione family, rosiglitazone and pioglitazone, have entered clinical practice since 1999. In this review we will try to present the current evidence concerning the cardioprotective role of these new antidiabetic regimens.