Glucagon-like peptide-1 receptor agonists and cardiovascular protection in type 2 diabetes: a pathophysiology-based review of clinical implications

Current Opinion in Cardiology
Harpreet S BajajSubodh Verma

Abstract

Cardiovascular outcome trials (CVOT) with glucagon-like peptide-1 receptor agonists (GLP-1 RA) have had variable results to date: with two CVOTs being positive and two concluding neutrality/safety results for primary cardiovascular outcome. Mechanistic insights delving into the pathophysiologic mechanisms that may link certain GLP-1 RA to cardioprotection may help define the application of this medication class in clinical practice based on the evidence of the CVOT data. We discuss the various mechanisms that have been postulated from animal and preclinical human studies to help explain the benefits observed in CVOTs with GLP-1 RA. Cardiovascular benefits of GLP-1 may be dependent on the complex interactions of this incretin hormone with the atherosclerotic pathways, either through its direct actions on the cardiovascular system or indirectly through intermediary actions on metabolism, energy transfer, inflammation or thrombosis. An indirect metabolic action of GLP-1 RA, via an initial step of achieving glucose homeostasis or balancing inter-organ energy metabolism, leading to favorable downstream effects on the inflammation-thrombosis pathways, finally impacting atherosclerosis, appears compelling. In addition to their metabol...Continue Reading

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Citations

Oct 27, 2018·Frontiers in Endocrinology·Silvano Paternoster, Marco Falasca
May 20, 2020·Trends in Molecular Medicine·Nathan O StitzielKarin E Bornfeldt

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