title: [Cardiovascular outcome clinical trials in type 2 diabetes mellitus: what are the epidemiological and methodological evidence and the first evaluations to date?].
abstract: Clinical trials of glucose-lowering strategies in patients with type 2 diabetes mellitus (T2DM) have shown a favorable effect of intensive glycemic control on microvascular complications but failed to show a clear benefit on cardiovascular events. In 2008, the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) have required stringent criteria to approve new glucose-lowering drugs, demanding proof of cardiovascular safety. As a result of these regulatory requirements, a number of cardiovascular outcome trials in T2DM have been conducted examining the cardiovascular safety of novel glucose-lowering drugs. Dipeptidyl peptidase 4 (DPP4) inhibitors, analogs of glucagon-like peptide 1 (GLP-1), and inhibitors of the renal sodium-glucose linked transporter-2 (SGLT2) are new classes of glucose-lowering drugs for subjects with T2DM. The results of the cardiovascular outcome trials comparing the DPP4 inhibitors saxagliptin, alogliptin, and sitagliptin or the GLP-1 analog lixisenatide to placebo have demonstrated that these drugs are safe. The results of a cardiovascular outcome trial comparing the SGLT2 inhibitor empagliflozin to placebo have been published. Notably, empagliflozin treatment has been associated with a significant reduction in the primary composite cardiovascular outcome. Although the question regarding the positive effect of glycemic control on cardiovascular risk is still unanswered, current evidence suggests that a multifactorial approach aimed at treating not only hyperglycemia but also classical cardiovascular risk factors is necessary in order to reduce the risk of cardiovascular events in patients with T2DM.
authors.affiliation: Dipartimento di Scienze Mediche e Chirurgiche, Università degli Studi "Magna Graecia", Catanzaro.
authors.forename: Teresa Vanessa
authors.initials: TV
authors.lastname: Fiorentino
authors.affiliation: Dipartimento di Scienze Mediche e Chirurgiche, Università degli Studi "Magna Graecia", Catanzaro.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Sesti
mesh_terms: D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control*; D002986:Clinical Trials as Topic; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D016896:Treatment Outcome