GLP-1 receptor agonists and their cardiovascular benefits - the role of the GLP-1 receptor.

Cardiovascular outcome trials (CVOT) revealed cardiovascular benefits for type 2 diabetes mellitus patients when treated with long-acting glucagon-like peptide-1 receptor (GLP-1R) agonists. In the last decade, major advances were made characterising the physiological effects of GLP-1 and its action on numerous target organs and tissues including brain, liver, kidney, heart, and blood vessels. However, the effects of GLP-1/GLP-1R agonists and the GLP-1 receptor on the cardiovascular system have not been fully elucidated. Herein we compare results from CVOT of distinct GLP-1R agonists and review pleiotropic clinical and preclinical data concerning cardiovascular protection by GLP-1 beyond glycaemic control. We address current knowledge on primary GLP-1/GLP-1R agonist actions on the heart, vasculature, inflammatory cells, and platelets and discuss evidence for GLP-1R-dependent vs -independent effects secondary to GLP-1 metabolites. We conclude that the favourable cardiovascular profile of GLP-1R agonists might favour expanded therapeutic use for treating cardiovascular disease even in non-diabetic populations.