Beyond Weight Loss: How GLP-1 RAs Established a Role in Cardiology in 2025

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are one of the fastest-growing drug families in medicine today. From humble beginnings as a method of insulin and glucagon management in patients with type 2 diabetes (T2D), GLP-1s have expanded into hepatology, cardiology, and even ophthalmology. Their role as an anti-inflammatory agent, coupled with their weight loss capabilities, has rocketed GLP-1 RAs to one of the top drugs in the industry.

Today, GLP-1 RAs are the backbone of endocrinology. But in recent years, they’ve also become a core component in a variety of cardiovascular diseases. Given their management of obesity, which can lead to sharp increases in heart failure risk, coronary artery disease, and stroke, GLP-1s have taken on almost as prominent a role in cardiology as in their home turf of endocrinology.

In June of 2025, the American College of Cardiology issued a statement on weight management drugs, with a spotlight on GLP-1s. In it, they noted semaglutide and tirzepatide, which have been proven substantially more effective in reducing cardiovascular disease risk than lifestyle changes and with fewer risks than procedure-based interventions. Although prior guidance has suggested GLP-1s as a secondary or even tertiary treatment method, this year’s release encourages clinicians to consider them as first-line options for eligible patients.1

Additionally, GLP-1s have received several key approvals from the US Food and Drug Administration (FDA), with oral semaglutide being granted an indication for the reduction of major adverse cardiovascular event risk in patients with T2D. Based on the SOUL trial, oral semaglutide’s approval marks the first oral GLP-1 medicine approved for a cardiovascular indication.2

Tirzepatide, a dual GIP/GLP-1 agonist, also made significant progress towards an FDA approval of its own, with Eli Lilly’s SURPASS-CVOT trial indicating its efficacy in reducing MACEs in patients with T2D and established atherosclerotic cardiovascular disease. The head-to-head trial compared tirzepatide to dulaglutide and displayed the former’s superior efficacy; risk of heart attack, stroke, or cardiovascular death was substantially lower with tirzepatide.3

However, in the face of such rapid advancement, some cardiologists encourage a more skeptical approach. Although great strides have been made in advancing cardiovascular outcomes with GLP-1 treatment, there are still factors limiting their reach. The most prominent of these issues is the number of clinical trials proving their efficacy. Many cardiologists have noted their hope – and expectation – for further case studies of GLP-1 RAs in the hopes of generating irrefutable evidence of their efficacy.

Editor’s Note: Le reports disclosures with Janssen, Pfizer, Novartis, Idorsia, Amarin, and Lexicon. Greene reports disclosures with Amgen, AstraZeneca, Bayer Healthcare Pharmaceuticals, Boehringer Ingelheim Pharmaceuticals, Cytokinetics, and others. Ezekowitz reports disclosures with Bayer, Merck, Amgen, Sanofi, Novartis, Cytokinetics, and others. Hansen and Mamic report no relevant disclosures.

References

1. Napoli N. American College of Cardiology Issues Guidance on Weight Management Drugs. American College of Cardiology. June 20, 2025. Accessed December 2, 2025. https://www.acc.org/About-ACC/Press-Releases/2025/06/20/14/11/American-College-of-Cardiology-Issues-Guidance-on-Weight-Management-Drugs

2. Novo Nordisk. FDA approves Novo Nordisk’s oral semaglutide for cardiovascular (CV) risk reduction in adults with type 2 diabetes who are at high risk, including those who have not had a prior CV event. PR Newswire. October 17, 2025. Accessed December 5, 2025. https://www.prnewswire.com/news-releases/fda-approves-novo-nordisks-oral-semaglutide-for-cardiovascular-cv-risk-reduction-in-adults-with-type-2-diabetes-who-are-at-high-risk-including-those-who-have-not-had-a-prior-cv-event-302588022.html

3. Eli Lilly. Lilly’s Mounjaro (tirzepatide), a GIP/GLP-1 dual agonist, demonstrated cardiovascular protection in landmark head-to-head trial, reinforcing its benefits in patients with type 2 diabetes and heart disease. July 31, 2025. Accessed December 5, 2025. https://investor.lilly.com/news-releases/news-release-details/lillys-mounjaro-tirzepatide-gipglp-1-dual-agonist-demonstrated