Cardiovascular events occurring in
type 2 diabetes (T2DM) are a major problem in clinical practice. In particular, the risk of
myocardial infarction (MI) presented by patients affected by T2DM without previous
cardiac events is similar to that of non-diabetic patients with previous MI. To reduce the elevated cardiovascular risk associated with T2DM, tight
glycemic control and aggressive
therapy against all known cardiovascular risk factors are strictly required. Despite the role played by
hyperglycemia in the pathogenesis of cardiovascular events, studies showing an improvement of cardiovascular outcomes by anti-hyperglycemic or
hypoglycemic agents are not conclusive. The United Kingdom Prospective Diabetes Study (UKPDS) demonstrated that in obese type 2 diabetic patients
metformin reduces the risk of MI more than sulphonylureas or
insulin. This observation identified
metformin as the first-line treatment for T2DM. The vasoprotective role of
metformin is largely independent of its
hypoglycemic action and has been ascribed to pleiotropic effects. The present review considers the putative beneficial action exerted by
metformin on arterial vessels by evaluating its effects on
lipids,
inflammation, hemostasis, endothelial and platelet function and vessel wall abnormalities. Furthermore, the molecular mechanisms of the beneficial metabolic and vascular effects of
metformin will be considered, with a particular attention for its ability to activate
AMP-activated protein kinase.