Advances in Cardiovascular Pharmacotherapy. X. Glucagon-Like Peptide-1 Receptor Agonists in Heart Failure and Mechanisms of Protection.

The first part of this two-part article discussed the physiology of glucagon-like peptide-1 (GLP-1), described the discovery and development of GLP-1 receptor agonists (RAs), examined the findings of major clinical trials and their substudies showing that GLP-1 RAs reduce major adverse cardiovascular events (MACE) in patients with type 2 diabetes and atherosclerotic cardiovascular disease, and finally, reviewed the evidence indicating that semaglutide protects against MACE in patients with obesity and established cardiovascular disease but not type 2 diabetes. This second part reviews recent clinical trials indicating that these drugs reduce symptom burden, increase exercise tolerance, and improve quality of life in patients with heart failure with preserved but not reduced ejection fraction. The article also discusses mechanisms by which GLP-1 RAs produce cardiovascular protection in patients with atherosclerotic cardiovascular disease or heart failure.