Resmetirom Shows Reduced MACE Compared to Semaglutide in MASLD Study

A recent study presented at the American College of Gastroenterology (ACG) 2026 Annual Scientific Meeting highlighted that resmetirom is linked to a significant reduction in major adverse cardiovascular events (MACE) compared to semaglutide in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) or metabolic dysfunction-associated steatohepatitis (MASH). The analysis, conducted by Dr. Jalal Samhoun from Florida Atlantic University, utilized data from the TriNetX Global Collaborative Network, focusing on a two-year follow-up period.

Historically, cardiovascular disease has been a leading cause of morbidity and mortality among patients with MASLD and MASH. Despite the increasing prevalence of these conditions, comparative data on cardiovascular outcomes between resmetirom and semaglutide had been lacking. Resmetirom, an oral thyroid hormone receptor-β agonist, received accelerated FDA approval in March 2024 for treating noncirrhotic MASH with moderate to advanced fibrosis, marking it as the first approved treatment for this condition. Conversely, semaglutide was approved in August 2025 based on its efficacy in achieving steatohepatitis resolution.

The study involved a carefully matched cohort of 4,253 patients receiving either resmetirom or semaglutide, with the primary outcome being MACE, which includes myocardial infarction, ischemic stroke, and all-cause mortality. At the one-year mark, resmetirom was associated with a 50% lower risk of MACE (HR 0.50) and a 71% reduction in all-cause mortality (HR 0.29). These benefits persisted at the two-year follow-up, with a 39% reduction in MACE risk (HR 0.61) and a 67% reduction in mortality (HR 0.33).

The implications of these findings are significant for both patients and healthcare providers, as they suggest that resmetirom may offer cardiovascular advantages in addition to its liver-related benefits. This could influence treatment decisions for patients with MASLD and MASH, who are at heightened risk for cardiovascular complications. However, it is essential to note that the study's retrospective nature limits the ability to establish causation, and further randomized trials are necessary to confirm these outcomes.

Looking ahead, ongoing research will be crucial to explore the long-term cardiovascular effects of resmetirom and to compare its efficacy directly against semaglutide in randomized controlled trials. As the understanding of MASLD and its implications for cardiovascular health evolves, these findings may pave the way for new therapeutic strategies in managing these complex conditions.