Viet Le, DMSc, PA-C, is a preventive cardiology PA at Intermountain Health and the former president of the Academy of Physician Associates in Cardiology.

Viet Le, DMSc, PA-C

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.

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.

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.

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.

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

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

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

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GLP-1 receptor agonists revolutionize treatment in cardiology, offering new hope for heart failure and related conditions beyond weight loss.

RX Review: Barriers, Real-World Implementation, and Future Directions in FCS

Despite boasting a pair of US Food and Drug Administration-approved therapies for 

, the disease still represents a significant area of unmet need in cardiology. 

, host Viet Le, DMSc, PA-C, a preventive cardiology PA at Intermountain Health and the former president of the Academy of Physician Associates in Cardiology, and panelist Christie Ballantyne, MD, chief of cardiovascular research at Baylor College of Medicine and principal investigator of the PALISADE trial, examine real-world barriers that continue to challenge optimal FCS management. 

Ballantyne notes that, despite advances in diagnosis and therapy, many patients still face obstacles related to genetic testing access, payer authorization, and fragmented care. These challenges can delay treatment initiation, even when patients meet clinical criteria. Accurate documentation and the use of validated diagnostic scoring systems are essential for navigating payer requirements, particularly after the approvals of olezarsen (Tryngolza) in late 2024, and plozasiran (Redemplo) on November 18, 2025, which both require clear diagnostic justification before coverage is granted.

The discussion turns toward practical strategies to improve real-world implementation. Ballantyne underscores the need for structured workflows that integrate primary care clinicians, lipid specialists, dietitians, and cardiologists. He highlights how early referrals, consistent follow-up, and comprehensive patient support can significantly reduce delays and improve adherence to therapy. Education remains a cornerstone of this effort, both for clinicians who may be unfamiliar with FCS and for patients who must manage a complex, lifelong condition.

The segment concludes with a hopeful outlook. Le and Ballantyne emphasize the future of FCS management will likely be defined by earlier diagnosis, improved care coordination, and ongoing innovation in therapy and testing. With the availability of targeted treatments for the first time, clinicians now have tools can meaningfully shift the trajectory of this severe condition. Continued investment in awareness, education, and interdisciplinary communication will be essential to ensure patients fully benefit from advancements introduced in 2025 and beyond.


Relevant disclosures for Ballantyne include Arrowhead Pharmaceuticals, Inois, Merck, Novartis, Novo Nordisk, New Amsterdam, Esperion, AstraZeneca, Eli Lilly, and others. Relevant disclosures for Le include Amarin, Bayer, Esperion, Idorsia, Janssen, Novo Nordisk, Novartis, Lexicon Pharmaceuticals, and Pfizer.

Arrowhead Pharmaceuticals. Arrowhead Pharmaceuticals Announces FDA Approval of REDEMPLO® (plozasiran) to Reduce Triglycerides in Adults with Familial Chylomicronemia Syndrome (FCS) - Arrowhead Pharmaceuticals, Inc. Arrowhead Pharmaceuticals, Inc. Published November 19, 2025. Accessed November 25, 2025. 

https://arrowheadpharma.com/news-press/arrowhead-pharmaceuticals-announces-fda-approval-of-redemplo-plozasiran-to-reduce-triglycerides-in-adults-with-familial-chylomicronemia-syndrome-fcs/

Virani SS, Morris PB, Agarwala A, et al. 2021 ACC Expert Consensus Decision Pathway on the Management of ASCVD Risk Reduction in Patients With Persistent Hypertriglyceridemia: A Report of the American College of Cardiology Solution Set Oversight Committee. 

US Food and Drug Administration. FDA approves Tryngolza (olezarsen). U.S. Food and Drug Administration. Published December 19, 2024. Accessed November 25, 2025. 

https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-drug-reduce-triglycerides-adult-patients-familial-chylomicronemia-syndrome

RX Review: Monitoring and Safety Considerations in FCS

As the cardiology community embraces the new, targeted-therapy era of management for 

, an integral aspect of conversations becomes safety and monitoring considerations.

, Le and Ballantyne shift attention to the safety considerations that accompany modern FCS therapies. Ballantyne reviews common adverse events encountered with injectable triglyceride-lowering agents, including olezarsen and plozasiran. These include injection site reactions, mild flu-like symptoms, transient hyperglycemia, and rare systemic complications. He notes safety profiles observed during clinical trials have been generally favorable, especially when compared with older triglyceride-lowering therapies. Regular monitoring, including lipid panels and periodic blood glucose assessments, provides an essential foundation for tracking response and detecting emerging issues early.

The conversation addresses the importance of patient counseling in promoting safe and sustained therapy use. Ballantyne emphasizes that clinicians should prepare patients for expected injection site reactions and reassure them that most reactions are mild and manageable. Structured follow-up visits allow clinicians to assess tolerability, address concerns, and adjust therapy as needed. Le and Ballantyne stress open communication improves adherence and helps ensure safety events do not lead to unnecessary discontinuation of therapy.

This segment concludes by outlining the central role of interdisciplinary collaboration in safety monitoring. Ballantyne reiterates safety monitoring is not merely a formality but a core component of modern FCS management ensuring patients benefit fully from these advanced therapies.


Explore the critical role of nutrition and pharmacologic therapies in managing hypertriglyceridemia and preventing pancreatitis effectively.

RX Review: Integrating New Therapies in FCS Treatment Algorithms

With new approvals, the most obvious question for clinicians often becomes: How do I fit this into treatment algorithms? 

This same question is being posed by cardiologists across the US as the field welcomed the second approval for 

 with the US Food and Drug Administration approval of plozasiran (Redemplo) in November 2025. 
In part 5 of our 

, host Viet Le, DMSc, PA-C, a preventive cardiology PA at Intermountain Health and the former president of the Academy of Physician Associates in Cardiology,  and panelist Christie Ballantyne, MD, chief of cardiovascular research at Baylor College of Medicine and principal investigator of the PALISADE trial, explore how the approvals of olezarsen (Tryngolza) and plozasiran reshape treatment algorithms for FCS. 

Ballantyne explains while these agents represent major scientific milestones, they must be incorporated with careful attention to patient needs and existing management principles. Historically, strict dietary restriction has been the cornerstone of therapy, often requiring patients to maintain extremely low-fat intake. Despite the availability of potent medications, Ballantyne reiterates nutritional management remains foundational because it supports medication effectiveness and helps mitigate triggers for pancreatitis.

The segment then focuses on practical integration of therapy. Ballantyne highlights the importance of consistent lipid monitoring and clear communication between lipid specialists, cardiologists, and nutritionists. Medication selection may vary according to patient preference, access considerations, safety profiles, and prior treatment response. The conversation underscores clinicians should provide structured education to ensure patients understand the ongoing role of diet, even when receiving advanced therapies.

Explore how the latest FDA approvals impact the management of FCS.

Viet Le, DMSc, PA-C

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