Tirzepatide Bests Semaglutide in Reducing Cardiovascular Events and Mortality in Patients With MASLD/MASH
A large real-world, propensity score–matched study of over 30,000 adults with metabolic-associated steatotic liver disease (MASLD) or metabolic-associated steatohepatitis (MASH), obesity, and type 2 diabetes mellitus (T2DM) found that treatment with tirzepatide was associated with significantly better cardiovascular and mortality outcomes compared to semaglutide.
The retrospective analysis, presented by Basil Jalamneh, MD, from the Cleveland Clinic, included 15,453 patients per treatment arm from the TriNetX global health research network. Both treatment groups were matched by demographics, comorbidities, medications, and laboratory values. Outcomes were assessed over 3 years and included cardiovascular events, all-cause mortality, hospitalizations, and liver disease progression.
Compared to semaglutide, tirzepatide was associated with:
- A 17% reduction in major adverse cardiovascular events (MACE) (RR, 0.83; 95% CI, 0.77–0.90)
- A 29% reduction in all-cause mortality (RR, 0.71; 95% CI, 0.57–0.90)
- A 23% reduction in all-cause hospitalizations (RR, 0.77; 95% CI, 0.73–0.82)
- A 25% reduction in myocardial infarction (RR, 0.75; 95% CI, 0.64–0.89)
- An 11% reduction in heart failure (RR, 0.89; 95% CI, 0.83–0.95)
- A 29% reduction in heart failure exacerbations (RR, 0.71; 95% CI, 0.59–0.84)
There were no statistically significant differences between the two treatments in risk of progression to cirrhosis (RR, 0.94; 95% CI, 0.86–1.02) or incidence of hepatocellular carcinoma (RR, 1.16; 95% CI, 0.81–1.65).
“In this large, propensity score–matched real-world cohort, tirzepatide treatment was associated with lower risks of cardiovascular-related outcomes, all-cause mortality, and all-cause hospitalizations compared to semaglutide,” the authors reported. These findings underscore the potential clinical benefit of dual GIP/GLP-1 receptor agonism for patients with complex metabolic comorbidities.
Reference
Jalamneh B, Abu-Hammour MN, Mohamed I, Hazem W, Sims O, Jung Chiang DJ. Comparative efficacy of tirzepatide vs. semaglutide on liver and cardiovascular related outcomes in patients with MASLD/MASH, obesity, and type 2 diabetes mellitus: a real-world cohort study. Presented at: American College of Gastroenterology Scientific Meeting; October 24-29, 2025; Phoenix, AZ.
