Advances in Cardiovascular Pharmacotherapy. IX. Protection Against Major Adverse Cardiovascular Events by Glucagon-like Peptide-1 Receptor Agonists in Type 2 Diabetes Mellitus and Obesity.

内容摘要

The glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a class of insulinotropic peptides that replicate the effects of endogenous GLP-1 but have a prolonged duration of action. GLP-1 RAs have had a remarkably profound impact on the treatment of type 2 diabetes and obesity because they substantially improve glycemic control and produce considerable weight loss. The U.S. FDA's requirement that pharmaceutical companies establish the cardiovascular safety of new type 2 diabetes medications coincided with the development of GLP-1 RAs and mandated that trials be conducted to assure that their adverse cardiovascular effect profiles were noninferior to placebo. This FDA requirement proved to be fortuitous because many of the newly developed GLP-1 RAs were shown to cause unanticipated cardiovascular and renal protective effects, which led to their expanded use beyond patients with type 2 diabetes or obesity to those with atherosclerotic cardiovascular disease, chronic kidney disease, and heart failure with preserved ejection fraction. This first of two articles on the cardiovascular pharmacology of GLP-1 RAs briefly discusses the physiology of GLP-1, describes the discovery and development of GLP-1 RAs, examines the findings of major clinical trials and their substudies showing that GLP-1 RAs reduce major adverse cardiovascular events in patients with or at high risk for atherosclerotic cardiovascular disease and type 2 diabetes, and finally, reviews the evidence indicating that the GLP-1 RA semaglutide protects against major adverse cardiovascular events in patients with obesity and established cardiovascular disease but not type 2 diabetes.