A recent real-world analysis presented at the American College of Gastroenterology 2026 Annual Scientific Meeting revealed that patients with metabolic dysfunction-associated steatohepatitis (MASH) treated with resmetirom faced a lower risk of major adverse cardiovascular events compared to those prescribed semaglutide.
In Plain English: The Clinical Takeaway
- MASH (Metabolic dysfunction-associated steatohepatitis): A progressive form of fatty liver disease characterized by liver inflammation and fibrosis (scarring), which can lead to cirrhosis or liver failure.
- MACE (Major adverse cardiovascular events): A composite clinical endpoint including myocardial infarction (MI), ischemic stroke, or all-cause mortality.
- Propensity-score matching: A statistical method used in retrospective studies to balance groups by accounting for confounding variables, allowing for a fairer comparison between different treatments.
TriNetX Database Powers 1:1 Propensity-Matched Cohort Analysis
Investigators utilized the TriNetX Global Collaborative Network to track adult patients diagnosed with MASLD or MASH alongside hepatic fibrosis. Researchers isolated cohorts of patients receiving either resmetirom or semaglutide. To minimize bias between the two patient groups, they performed a 1:1 propensity score matching protocol. This matching controlled for baseline demographics, cardiovascular risk factors, metabolic comorbidities, liver disease characteristics, medications, and laboratory values.
Following this rigorous alignment, the final analysis evaluated 4,253 patients in each treatment arm. The primary endpoint was MACE, while secondary outcomes tracked all-cause mortality, MI, atrial fibrillation (AF), and heart failure (HF).
| Outcomes Monitored | 1-Year Hazard Ratio (HR) | 2-Year Hazard Ratio (HR) |
|---|---|---|
| Major Adverse Cardiovascular Events (MACE) | HR, 0.50 (95% CI, 0.32-0.80; P = .003) | HR, 0.61 (95% CI, 0.41-0.89; P = .01) |
| All-Cause Mortality | HR, 0.29 (95% CI, 0.16-0.54; P < .001) | HR, 0.33 (95% CI, 0.20-0.55; P < .001) |
| Heart Failure (HF) | HR, 0.64 (95% CI, 0.42-0.99; P = .04) | Not statistically significant at 2 years |
At the one-year mark, data indicated that resmetirom correlated with lower risks of MACE, all-cause mortality, and heart failure relative to semaglutide. These protective associations persisted at the two-year evaluation for both MACE and all-cause mortality. Meanwhile, rates of MI and AF did not differ significantly between the two cohorts across the observation window, though AF demonstrated a nonsignificant trend favoring resmetirom by year two.
Despite these findings, study authors noted important methodological limitations. Because the analysis was retrospective and drew on electronic health records, it establishes associations rather than definitive causation. Propensity matching can only control for variables recorded in the database, leaving room for unmeasured residual confounding. Furthermore, while semaglutide has shown cardiovascular benefit in a randomized trial, no randomized cardiovascular outcome data for resmetirom have been published.
Contraindications & When to Consult a Doctor
Patients managing MASH or liver fibrosis should not alter prescribed therapeutic regimens based on observational data alone. Consult your hepatologist or primary care physician prior to considering medication adjustments. Seek immediate medical attention if you experience acute symptoms.
The retrospective evaluation was presented by J. Samhoun and colleagues at the American College of Gastroenterology 2026 Annual Scientific Meeting held in Nashville, Tennessee.
References
- Samhoun J, et al. Cardiovascular outcomes of resmetirom versus semaglutide in patients with MASLD/MASH: a propensity-matched real-world analysis. Presented at: American College of Gastroenterology 2026 Annual Scientific Meeting; October 9-14, 2026; Nashville, TN.
- Harrison SA, Bedossa P, Guy CD, et al. A phase 3, randomized, controlled trial of resmetirom in NASH with liver fibrosis. N Engl J Med. 2024;390(6):497-509.
- Sanyal AJ, Newsome PN, Kliers I, et al. Phase 3 trial of semaglutide in metabolic dysfunction-associated steatohepatitis. N Engl J Med. 2025;392(21):2089-2099.
- Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med. 2023;389(24):2221-2232.
