title: Incretin-based therapies and cardiovascular risk.
abstract: 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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  Taken together, available data suggest that incretin-based therapies could prevent cardiovascular disease via multiple mechanisms.
authors.affiliation: Diabetes Agency and Obesity Agency, Careggi Teaching Hospital, Florence, Italy. edoardo.mannucci@unifi.it
authors.forename: Edoardo
authors.initials: E
authors.lastname: Mannucci
authors.forename: Ilaria
authors.initials: I
authors.lastname: Dicembrini
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000517:prevention & control*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D042783:Endothelial Cells / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000627:therapeutic use*; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D054795:Incretins / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000187:drug effects; D010865:Pilot Projects; D018027:Receptors, Glucagon / Q000819:agonists*
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D054795:Incretins; D018027:Receptors, Glucagon; D052216:Glucagon-Like Peptide 1