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Background <p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent condition with significant cardiometabolic and hepatic risks. Tirzepatide, a dual GLP-1/GIP receptor agonist, shows promise in MASLD, but real-world comparative data against sodium-glucose cotransporter-2 inhibitors (SGLT2is) are lacking.</p> Methods <p>In this multicenter, retrospective, propensity score-matched cohort study using the TriNetX US Collaborative Network, we compared outcomes in 43,743 new tirzepatide initiators versus 43,743 matched SGLT2i users with MASLD and ≥ 1 metabolic comorbidity. Propensity Score Matching (1:1, caliper 0.1) balanced &gt; 50 covariates. Primary outcomes included all-cause mortality, hospitalization, major adverse cardiovascular events (MACE), major adverse liver outcomes (MALO), and major adverse kidney events (MAKE) at 1- and 3-year follow-up, analyzed via Kaplan–Meier estimation and Cox proportional hazards models.</p> Results <p>Tirzepatide was associated with significantly lower risks versus SGLT2is. At 1-year follow-up (<i>n</i> = 43,743 per group), all-cause mortality events were 144 (cumulative incidence 0.48%, KM event-free survival 99.52%) with tirzepatide versus 533 (1.38%, 98.62%) with SGLT2i (HR 0.328, 95% CI 0.272–0.394; log-rank p &lt; 0.0001). All-cause hospitalization occurred in 3033 versus 7143 (HR 0.460, 95% CI 0.441–0.480). MACE events were 1064 versus 2376 (HR 0.506, 95%CI 0.471–0.544). MALO events were 149 versus 465 (HR 0.379, 95% CI 0.315–0.456). Hepatic failure and ascites also favored tirzepatide, while MAKE, varices, and hepatic encephalopathy showed no significant differences. Benefits persisted at 3&#xa0;years (<i>n</i> = 39,838 per group): mortality 208 versus 963 (HR 0.374, 95% CI 0.321–0.436); hospitalization 3723 versus 9548 (HR 0.528, 95%CI 0.508–0.549); MACE 1260 versus 3282 (HR 0.545, 95%CI 0.510–0.582); and MALO 220 versus 726 (HR 0.478, 95%CI 0.410–0.558).</p> Conclusions <p>In this large real-world MASLD cohort, tirzepatide was associated with substantial reductions in mortality, hospitalizations, cardiovascular, and liver-related events compared to SGLT2is. These observational findings suggest potential advantages of tirzepatide and warrant prospective validation in randomized trials.</p> Graphical abstract <p></p>

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

  • 期刊论文

  • 发表日期：

    2026年7月3日

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  • Ibrahim Khalil,
  • Pallab Sarker,
  • Nabila Nur,
  • Md. Imran Hossain,
  • Aizaz Anwar Khalid,
  • Sajjad Ghanim Al-Badri,
  • Mst. Mahmuda Akter,
  • Manisha Das,
  • Mohd Turzo Rahman

摘要

Background

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent condition with significant cardiometabolic and hepatic risks. Tirzepatide, a dual GLP-1/GIP receptor agonist, shows promise in MASLD, but real-world comparative data against sodium-glucose cotransporter-2 inhibitors (SGLT2is) are lacking.

Methods

In this multicenter, retrospective, propensity score-matched cohort study using the TriNetX US Collaborative Network, we compared outcomes in 43,743 new tirzepatide initiators versus 43,743 matched SGLT2i users with MASLD and ≥ 1 metabolic comorbidity. Propensity Score Matching (1:1, caliper 0.1) balanced > 50 covariates. Primary outcomes included all-cause mortality, hospitalization, major adverse cardiovascular events (MACE), major adverse liver outcomes (MALO), and major adverse kidney events (MAKE) at 1- and 3-year follow-up, analyzed via Kaplan–Meier estimation and Cox proportional hazards models.

Results

Tirzepatide was associated with significantly lower risks versus SGLT2is. At 1-year follow-up (n = 43,743 per group), all-cause mortality events were 144 (cumulative incidence 0.48%, KM event-free survival 99.52%) with tirzepatide versus 533 (1.38%, 98.62%) with SGLT2i (HR 0.328, 95% CI 0.272–0.394; log-rank p < 0.0001). All-cause hospitalization occurred in 3033 versus 7143 (HR 0.460, 95% CI 0.441–0.480). MACE events were 1064 versus 2376 (HR 0.506, 95%CI 0.471–0.544). MALO events were 149 versus 465 (HR 0.379, 95% CI 0.315–0.456). Hepatic failure and ascites also favored tirzepatide, while MAKE, varices, and hepatic encephalopathy showed no significant differences. Benefits persisted at 3 years (n = 39,838 per group): mortality 208 versus 963 (HR 0.374, 95% CI 0.321–0.436); hospitalization 3723 versus 9548 (HR 0.528, 95%CI 0.508–0.549); MACE 1260 versus 3282 (HR 0.545, 95%CI 0.510–0.582); and MALO 220 versus 726 (HR 0.478, 95%CI 0.410–0.558).

Conclusions

In this large real-world MASLD cohort, tirzepatide was associated with substantial reductions in mortality, hospitalizations, cardiovascular, and liver-related events compared to SGLT2is. These observational findings suggest potential advantages of tirzepatide and warrant prospective validation in randomized trials.

Graphical abstract