ACG 2025: Tirzepatide bests semaglutide for CV, liver outcomes in real-world cohort study

For patients with metabolic-associated steatotic liver disease (MASLD)/metabolic-associated steatohepatitis (MASH), obesity, and T2DM, tirzepatide may offer greater cardiovascular benefit than semaglutide. Over two years, tirzepatide was associated with lower risks of all-cause mortality, hospitalization, acute MI, and heart failure (HF), while liver outcomes were similar between drugs. These findings, presented at ACG 2025, highlight the potential advantage of dual GLP-1/GIP agonism for high-risk metabolic populations.

Study details: This observational, real-world study used the TriNetX network to compare tirzepatide and semaglutide in adults with MASLD/MASH, obesity, and T2DM. Approximately 14,000 patients per group were included in a new-user, active-comparator, 1:1 propensity-matched design. Follow-up extended to 24 months, assessing CV and liver-related outcomes.

Results: Compared with semaglutide, tirzepatide was associated with:

• 17% lower risk of MACE: risk ratio (RR), 0.83; 95% confidence interval (CI), 0.77–0.90
• 29% lower all-cause mortality: RR, 0.71; 95% CI, 0.57–0.90
• 23% lower hospitalization risk: RR, 0.77; 95% CI, 0.73–0.82
• 25% lower MI risk: RR, 0.75; 95% CI, 0.64–0.89
• 11% lower HF risk: RR, 0.89; 95% CI, 0.83–0.95
• 29% lower HF exacerbations:RR, 0.71; 95% CI, 0.59–0.84

No significant differences were observed for cirrhosis progression (RR, 0.94; 95% CI, 0.86–1.02) or hepatocellular carcinoma incidence (RR, 1.16; 95% CI, 0.81–1.65).

Source:

Jalamneh B, et al. “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” [Abstract]. Presented at ACG 2025 Annual Scientific Meeting. https://acg2025.eventscribe.net/fsPopup.asp?PresentationID=1687974&mode=presInfo. Accessed October 30, 2025.