Efficacy of tirzepatide versus SGLT2 inhibitors in metabolic dysfunction-associated steatotic liver disease (MASLD): a multicenter propensity-matched real-world study

In this large matched real-world cohort, tirzepatide was associated with lower risks of death, hospitalization, cardiovascular events, and major adverse liver outcomes than SGLT2 inhibitors at both 1 and 3 years. The study compared 43,743 matched pairs with MASLD from US electronic health records. As an observational analysis, it suggests but does not prove that tirzepatide is superior.

Journal article — multicenter retrospective propensity-matched cohort study. Population: MASLD patients with ≥1 metabolic comorbidity in the TriNetX US Collaborative Network. Sample size: 43,743 per group (1-year); 39,838 per group (3-year). Follow-up: 1-year and 3-year follow-up. Interventions: Tirzepatide.

At 1 year, all-cause mortality events were 144 with tirzepatide versus 533 with SGLT2i (HR 0.328); all-cause hospitalization was 3033 versus 7143 (HR 0.460); MACE was 1064 versus 2376 (HR 0.506); and MALO was 149 versus 465 (HR 0.379). Hepatic failure and ascites favored tirzepatide, while MAKE, varices, and hepatic encephalopathy showed no significant differences. At 3 years, mortality was 208 versus 963 (HR 0.374), hospitalization 3723 versus 9548 (HR 0.528), MACE 1260 versus 3282 (HR 0.545), and MALO 220 versus 726 (HR 0.478).

For researchers studying tirzepatide, this paper provides large real-world comparative evidence that tirzepatide may outperform SGLT2 inhibitors across mortality, hospitalization, cardiovascular, and liver outcomes in MASLD. It does not establish a causal effect or provide evidence for a specific dose or duration of treatment, and randomized trial confirmation is still needed.

Key findings

• At 1 year, tirzepatide was associated with lower all-cause mortality than SGLT2 inhibitors (144 vs 533 events; HR 0.328, 95% CI 0.272–0.394).
• All-cause hospitalization at 1 year was lower with tirzepatide (3033 vs 7143; HR 0.460, 95% CI 0.441–0.480).
• MACE at 1 year favored tirzepatide (1064 vs 2376; HR 0.506, 95% CI 0.471–0.544).
• Major adverse liver outcomes at 1 year favored tirzepatide (149 vs 465; HR 0.379, 95% CI 0.315–0.456).
• Benefits persisted at 3 years, with mortality HR 0.374 (208 vs 963) and MALO HR 0.478 (220 vs 726).
• MAKE, varices, and hepatic encephalopathy showed no significant differences between groups.

Limitations

• The abstract reports no author-stated limitations; as a retrospective observational study it is subject to residual confounding despite propensity matching.
• Propensity matching balances measured covariates but cannot fully adjust for unmeasured confounders such as medication adherence or lifestyle factors.
• TriNetX electronic health record data may include coding errors or misclassification of outcomes.
• No randomization was used, so causal conclusions cannot be drawn and prospective validation is required.

The record

• Journal: Hepatology international
• Published: 2026-07-03
• PMID: 42397506 — DOI: 10.1007/s12072-026-11122-3
• Author countries: Bangladesh, Iraq, Pakistan, USA

Peptide profiles: Tirzepatide.

All indexed evidence: Tirzepatide trials & papers.

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