Q&A: Understanding the Role of Tirzepatide, Semaglutide in Cardiovascular Disease

Ambarish Pandey, MD, associate professor of cardiology in internal medicine at the University of Texas Southwestern Medical Center in Dallas, Texas, sat down with Drug Topics ahead of the American Society for Preventive Cardiology Congress on CVD Prevention to discuss recent advancements in the understanding of glucagon-like peptide-1 (GLP-1) therapies’ mechanism of action, clinical guidelines for GLP-1 use, and more.

Drug Topics: What advancements in the understanding of GLP-1 receptor agonists’ mechanisms of action have influenced their use in the management of diabetes and obesity?

As evidence emerges, so too will stronger indications for the use of GLP-1 medications in cardiovascular disease. | Image credit: Siarhei - stock.adobe.com

Ambarish Pandey, MD: The way these drugs work is by…suppressing appetite and inducing early satiety, which reduces overall caloric intake. I think that is largely considered a safe way to lose weight, because it is aligned with other, more tested caloric restriction strategies that have been used in the past.

I think we still don't completely understand how these drugs modify cardiovascular risk, particularly the risk of major adverse cardiovascular events; much more needs to be done to better understand [if] there are direct benefits of these therapies with reducing or mitigating cardiovascular risk. I think the weight loss effects are likely through its effect on the incretion action and inducing satiety.

Drug Topics: How have clinical guidelines for the use of GLP-1 receptor agonists changed over time, and what implications do these changes have for their use in clinical practice?

Pandey: The guidelines are evolving, and as more and more evidence is coming out for the use of these therapies for mitigation of cardiovascular risk, I think we will see stronger indications for using these medications in individuals with prevalent cardiovascular disease. There's evidence for efficacy of semaglutide in HFpEF, or heart failure with preserved ejection fraction, and I think there's increasing evidence that they [GLP-1s] may actually have a lot of value in reducing the risk of adverse cardiovascular events in individuals with prevalent cardiovascular diseases.

READ MORE: SGLT2i, GLP-1RA Combination Therapy Offers Robust Protection Against Cardiovascular, Kidney Disease

As more evidence from tirzepatide and other trials comes out, I think we will see greater uptake and guidelines for these therapies. And we'll also potentially see indications for prevention of kidney disease; the data for kidney disease is coming out to be very favorable, particularly for semaglutide.

The American Society for Preventive Cardiology Congress on CVD Prevention was held August 2 to August 4 in Salt Lake City, Utah. Click here for more of our coverage.