Harnessing the incretin system beyond glucose control: potential cardiovascular benefits of GLP-1 receptor agonists in type 2 diabetes.
The management of type 2 diabetes continues to evolve as new data emerge. Although glycaemic control is still important, other risk factors--such as hypertension, dyslipidaemia and obesity--must also be addressed in order to reduce the long-term risks of cardiovascular complications and mortality. In this context, targeting the incretin system, and glucagon-like peptide-1 (GLP-1) in particular, has generated much interest. GLP-1 is released from the gut in response to food ingestion and plays a crucial role in glucose homeostasis. GLP-1 receptors are expressed in the heart and vasculature, prompting evaluation of their physiological role and pharmacological stimulation, both in healthy and disease states. These studies indicate that GLP-1 and GLP-1-based therapies appear to have direct, beneficial effects on the cardiovascular system, in addition to their glucose-lowering properties, such as modulation of blood pressure, endothelial function, and myocardial contractility. Intriguingly, some of these effects appear to be independent of GLP-1 receptor signalling. Data from clinical studies of the GLP-1 receptor agonists, exenatide and liraglutide on cardiovascular risk factors, in patients with type 2 diabetes are also promising and the results from prospective studies to assess cardiovascular outcomes are eagerly awaited.
Université de Nantes, CHU de Nantes, Hôpital Guillaume et René-Laennec, boulevard Jacques-Monod, Saint-Herblain, 44093 Nantes cedex 1, France. bertrand.cariou@univ-nantes.fr
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D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects; D000077270:Exenatide; D052216:Glucagon-Like Peptide 1 / Q000819:agonists* / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D054795:Incretins / Q000494:pharmacology*; D000069450:Liraglutide; D051379:Mice; D010455:Peptides / Q000494:pharmacology; D011446:Prospective Studies; D012307:Risk Factors; D016896:Treatment Outcome; D014688:Venoms / Q000494:pharmacology
D001786:Blood Glucose; D054873:Dipeptidyl-Peptidase IV Inhibitors; D054795:Incretins; D010455:Peptides; D014688:Venoms; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide