Oral antidiabetic agents: anti-atherosclerotic properties beyond glucose lowering?

Type 2 diabetes is associated with substantially increased cardiovascular mortality. The need to reduce the progression of atherosclerosis alongside lowering blood glucose levels is now well established. Ideally, pharmaceutical treatment should address both of these needs. This review summarises current evidence of the anti-atherosclerotic effects exerted by oral antidiabetic agents. Metformin has so far consistently succeeded in reducing cardiovascular morbidity and mortality and exerting beneficial effects on lipids. Of the new agents, thiazolidinediones (rosiglitazone and pioglitazone) have been most widely studied. They have a favourable effect on fat distribution and improve lipid profile, fibrinolysis and endothelial function. Moreover, they reduce blood pressure and inflammatory markers, attenuate the progression of carotid intima-media thickness (CIMT) and may reduce the rates of coronary restenosis following percutaneous coronary intervention. Glinides (repaglinide and nateglinide) have also been documented to improve endothelial function and lipid profile, to reduce oxidative stress, platelet activity and inflammatory markers, and to diminish the progression of CIMT. Finally, acarbose may significantly reduce new cases of hypertension and cardiovascular events, as well as diminishing the progression of CIMT in patients with impaired glucose tolerance. Interestingly, some of these beneficial effects appear to be independent of the antidiabetic action. Thus, oral antidiabetic agents are now emerging as useful tools for the attenuation of the atherosclerotic activity and for the protection of the vasculature in patients with type 2 diabetes.