ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2011) 26 S9.2

GLP-1 and the cardiovascular system

Michaela Diamant

Department of Internal Medicine, VU University Medical Centre, Amsterdam, The Netherlands.

The gut hormone glucagon-like peptide (GLP)-1 lowers blood glucose by stimulating meal-related insulin secretion and lowering hyperglucagonaemia in a glucose-dependent manner. Currently, injectable GLP-1 receptor agonists (GLP-1RA) and oral inhibitors of the dipeptidyl peptidase (DPP)-4 enzyme, that degrades native GLP-1, are successfully employed in the treatment of type 2 diabetes (T2DM). Clinically relevant extrapancreatic effects of GLP-1 (RA) involve slowing down gastric emptying, inducing satiety, reducing food intake and decreasing bodyweight. Additional benefits are improvement of islet-cell function. More recently, direct effects on the cardiovascular (CV) system have been described. Indeed, GLP-1 receptors are present on vascular cells and cardiomyocytes. In rodents, GLP-1, but also GLP-1RA and DPP-4 inhibition, were shown to reduce myocardial infract size in ischaemia-reperfusion models and pretreatment with GLP-1 improved cardiac function after ischaemia/reperfusion injury. In small-sized human studies, GLP-1 improved cardiac function in post-myocardial infarction patients with left ventricular dysfunction and in those with heart failure. Also, DPP-4 inhibition resulted in an improved myocardial response to dobutamine stress in patients with coronary artery disease. In addition, beneficial effects of GLP-1 (RA) were observed on endothelial function. However, to date it is unclear whether these effects are directly mediated by activation of the GLP-1 receptor or by another mechanisms involving the metabolite GLP-1 (9–36). Similarly, it is unknown whether the GLP-1 effects are direct or whether the improvement of systemic metabolism is the key contributor to the observed beneficial effects. GLP-1 (RA) improved obesity-related CV risk factors, thus theoretically reducing CV risk. However, the recently initiated large-sized long-term outcome studies with the various incretin-based compounds should ultimately determine whether these promising agents indeed reduce the excessive risk of CV disease in people with T2DM.

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