Impact of GLP-1 and GLP-1 Receptor Agonists on Cardiovascular Risk Factors in Type 2 Diabetes

Abstract

Type 2 diabetes (T2D) is associated with increased cardiovascular disease and mortality. Most diabetes treatments have not proven to reduce this risk and may be associated with worsening of specific cardiovascular risk factors. GLP-1 receptor agonists (GLP-1R agonists) are new incretin-based therapies for the treatment of T2D. They improve glucose control by stimulating insulin secretion and suppressing glucagon release, both in a glucose-dependent manner. There are two GLP-1R agonists approved for the treatment of T2D: once daily liraglutide and twice daily exenatide, both administered by sc injection. Based on recent clinical trials, GLP-1R agonists suggest having a protective role in cardiovascular risk factors besides improving glycemic control, compared to placebo and to standard diabetes therapies. Both liraglutide and exenatide have demonstrated to induce clinically significant weight loss and to reduce systolic blood pressure. Liraglutide also has a positive effect on the lipid profile and cardiovascular risk biomakers. Furthermore, recent data shows a direct effect of GLP-1 and its metabolites in the vascular endothelium and the myocardium, leading to vasodilator effects and improved cardiac function in humans with acute myocardial infarction or congestive heart failure. GLP-1R agonists have a positive impact on cardiovascular risk factors otherwise not addressed by most standard diabetes therapies. Whether these new compounds actually decrease cardiovascular disease and mortality remains to be demonstrated in outcome studies.