Clinical benefits of tirzepatide in patients with steatotic liver disease and cardiometabolic dysfunction

Tirzepatide use was associated with substantially lower risks of liver-related complications in adults with steatotic liver disease and cardiometabolic dysfunction. In a large propensity-matched retrospective analysis, patients prescribed tirzepatide had a markedly lower incidence of major adverse liver outcomes than matched controls. The authors say these findings support prospective validation of tirzepatide's potential hepatic benefits.

Journal article — Retrospective propensity-matched cohort study. Population: Adults with steatotic liver disease and cardiometabolic dysfunction identified in the TriNetX Global Collaborative Network between June 1, 2022, and April 25, 2025.. Sample size: 54,882 matched individuals. Interventions: tirzepatide.

Among 54,882 matched individuals, tirzepatide was associated with a lower incidence of major adverse liver outcomes compared with the control group (HR, 0.32; 95% CI, 0.28-0.37). Tirzepatide use was associated with reductions in composite decompensated liver events (HR, 0.31; 95% CI, 0.26-0.36), esophageal variceal bleeding (HR, 0.39; 95% CI, 0.26-0.58), hepatic encephalopathy (HR, 0.27; 95% CI, 0.21-0.34), ascites-related complications (HR, 0.28; 95% CI, 0.23-0.33), hepatocellular carcinoma (HR, 0.36; 95% CI, 0.25-0.53), and liver transplantation (HR, 0.16; 95% CI, 0.08-0.33). Tirzepatide was also associated with lower all-cause mortality (HR, 0.22; 95% CI, 0.18-0.28), major adverse cardiac events (HR, 0.46; 95% CI, 0.40-0.52), and major adverse kidney events (HR, 0.26; 95% CI, 0.22-0.32).

This paper provides real-world evidence linking tirzepatide to lower risks of liver and cardiometabolic complications in people with steatotic liver disease and cardiometabolic dysfunction. For researchers studying tirzepatide, it identifies possible hepatic benefits worth testing in prospective trials. It does not establish causality, dosing effects, or a formal indication for tirzepatide in steatotic liver disease.

Key findings

• Tirzepatide was associated with a lower incidence of major adverse liver outcomes versus controls (HR, 0.32; 95% CI, 0.28-0.37).
• Tirzepatide was associated with lower composite decompensated liver events (HR, 0.31; 95% CI, 0.26-0.36), esophageal variceal bleeding (HR, 0.39; 95% CI, 0.26-0.58), hepatic encephalopathy (HR, 0.27; 95% CI, 0.21-0.34), and ascites-related complications (HR, 0.28; 95% CI, 0.23-0.33).
• Tirzepatide was associated with lower hepatocellular carcinoma (HR, 0.36; 95% CI, 0.25-0.53) and liver transplantation (HR, 0.16; 95% CI, 0.08-0.33).
• Tirzepatide was associated with lower all-cause mortality (HR, 0.22; 95% CI, 0.18-0.28), major adverse cardiac events (HR, 0.46; 95% CI, 0.40-0.52), and major adverse kidney events (HR, 0.26; 95% CI, 0.22-0.32).

Limitations

• Retrospective observational design cannot exclude residual confounding despite propensity-score matching.
• Analysis relied on TriNetX electronic health record data, so outcome ascertainment depends on coding accuracy.
• Follow-up duration is not reported, and the authors call for prospective validation of hepatic benefits.

The record

• Journal: Communications medicine
• Published: 2026-06-29
• PMID: 42373761 — DOI: 10.1038/s43856-026-01759-4
• Author countries: Taiwan

Peptide profiles: Tirzepatide.

All indexed evidence: Tirzepatide trials & papers.

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