Cardiovascular outcome trials revealed cardiovascular benefits for type 2 diabetes mellitus patients when treated with long-acting glucagon-like peptide-1 (GLP-1) receptor agonists. In the last decade, major advances were made characterising the physiological effects of GLP-1 and its action on numerous targets including brain, liver, kidney, heart and blood vessels. However, the effects of GLP-1 and receptor agonists, and the GLP-1 receptor on the cardiovascular system have not been fully elucidated. We compare results from cardiovascular outcome trials of GLP-1 receptor agonists and review pleiotropic clinical and preclinical data concerning cardiovascular protection beyond glycaemic control. We address current knowledge on GLP-1 and receptor agonist actions on the heart, vasculature, inflammatory cells and platelets, and discuss evidence for GLP-1 receptor-dependent versus independent effects secondary of GLP-1 metabolites. We conclude that the favourable cardiovascular profile of GLP-1 receptor agonists might expand their therapeutic use for treating cardiovascular disease even in non-diabetic populations. LINKED ARTICLES: This article is part of a themed issue on GLP1 receptor ligands (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.4/issuetoc.
Keywords: GLP-1 metabolites; cardiovascular outcome trial; cardiovascular protection; diabetes mellitus; glucagon-like peptide-1 receptor.
© 2021 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.