Incretin-based therapies and cardiovascular risk

Background: Glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase 4 (DPP4) inhibitors are currently used as glucose-lowering agents in type 2 diabetes, due to their effects on insulin and glucagon secretion. These agents, which are effective in improving glucose control, could also have a beneficial effect on the incidence of cardiovascular events. The analysis of major cardiovascular events reported during trials with metabolic endpoints shows a significant reduction of risk with both classes of drugs. Longer-term trials specifically designed to assess the effects of GLP-1 receptor agonists and DPP4 inhibitors on major cardiovascular events are currently ongoing. Scope: In order to elucidate potential mechanisms of cardiovascular protection with incretin-based therapies, a Medline search (any date up to December 15th, 2011) was performed using the terms 'cardiovascular' and ('DPP-4' or 'GLP-1' or any single name of incretin-based drugs); papers which were considered relevant for the aim of this review were selected by the authors, on the basis of their judgment. Findings: Incretin-based drugs have beneficial effects on cardiovascular risk factors, such as blood pressure and, to a lesser extent, cholesterol and triglyceride. GLP-1 receptor agonists also reduce body weight. A number of experimental studies has suggested that GLP-1 has direct, beneficial effects on myocardial and endothelial cells, but some of these actions could be mediated via GLP-1 receptor-independent pathways. Available experimental evidence, together with a few pilot studies in humans, shows that GLP-1 receptor agonists and DPP4 inhibitors are capable of ameliorating myocardial function and protect myocardiocytes from ischemic damage, independent of their glucose-lowering effects. Furthermore, both classes of drugs enhance endothelial function. In addition, DPP4 inhibitors increase the availability of endothelial progenitor cells, via a GLP-1 receptor-independent pathway. Conclusion: Taken together, available data suggest that incretin-based therapies could prevent cardiovascular disease via multiple mechanisms.