Cardiovascular Health Benefits of GLP-1

Glucagon-like peptide 1 (GLP-1) receptor agonists are anti-hyperglycemic drugs that are now widely used for weight loss. They are also getting a lot of attention for their cardiovascular health benefits. Indirect effects on cardiovascular health are achieved through reduced body weight, blood pressure, blood sugar, and unhealthy cholesterol levels. A number of direct benefits have also bee demonstrated in clinical trials. The bottom line: GLP-1 drugs are associated with a reduced risk of heart attack and stroke.

A 2023 study concluded that weekly use of semaglutide, a GLP-1 agonist, reduced the risk of stroke, heart attack, and death from heart disease by 20% compared to placebo in people without diabetes. The study included 17,604 subjects with preexisting cardiovascular disease and a body mass index (BMI) of 27. 

Similar studies have shown the cardiovascular health benefits of other GLP-1 agonists. The LEADER trial significantly reduced the incidence of major cardiovascular events in over 9,000 patients with high cardiovascular risk. In the SUSTAIN-6 trial, semaglutide reduced the risk of stroke by almost 40%. Several other studies have shown similar results.

Several mechanisms help explain their direct cardiovascular health benefits. First, GLP-1 receptor agonists act primarily by enhancing postprandial insulin secretion and suppressing glucagon release, improving glycemic control. Second, GLP-1 drug binding to heart muscle cells increases glucose uptake and utilization, reduces oxidative stress, and inhibits heart muscle cell programmed death (apoptosis). Third, dilation of arteries in the heart increases coronary blood flow; in the body, this lowers blood pressure, decreasing cardiac work and oxygen requirement. Fourth, a meta-analysis of 35 clinical trials demonstrated a modest reduction in LDL cholesterol, total cholesterol, and triglycerides in patients treated with GLP-1 RAs compared to controls (https://pubmed.ncbi.nlm.nih.gov/25554560/).

GLP-1 agonist drugs have major cardiovascular health benefits but are not for everyone. They are expensive and have a variety of side effects and risks. We are all encouraged to do our homework and discuss the risks and benefits with our physicians!

Note: Although I am a physician, the content in this article is not meant to diagnose, treat, cure or prevent illness or disease in the reader – it is for educational purposes only.

References

1. Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev (2007) 87(4):1409–39. doi: 10.1152/physrev.00034.2006. https://pubmed.ncbi.nlm.nih.gov/17928588/
2. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide improved cardiovascular health in people without diabetes. NEJM 2023;389:2221-32. https://www.nejm.org/doi/full/10.1056/NEJMoa2307563#:~:text=Agonists%20of%20the%20glucagon%2Dlike,are%20at%20high%20cardiovascular%20risk.&text=Although%20these%20agents%20affect%20a,who%20did%20not%20have%20diabetes.&text=In%20the%20Semaglutide%20Effects%20on,who%20did%20not%20have%20diabetes.
3. Marso SP, Bain SC, Consoli A, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. NEJM 2016;375:1834-44. https://www.nejm.org/doi/full/10.1056/NEJMoa1607141.
4. Sun F,Wu S,Wang J, et al. Effect of glucagon-like peptide-1 receptor agonists on lipid profiles among type 2 diabetes: a systematic review and network meta-analysis. Clin Ther (2015) 37(1):225–41.e8. doi: 10.1016/j.clinthera.2014.11.008. https://pubmed.ncbi.nlm.nih.gov/25554560/