Tirzepatide, semaglutide both improve liver outcomes in adults with T2D, obesity

6 hours ago
Tirzepatide, semaglutide both improve liver outcomes in adults with T2D, obesity

Tirzepatide and injectable semaglutide deliver similar effectiveness against liver disease progression and major adverse liver outcomes (MALO) among adults with overweight or obesity and type 2 diabetes (T2D), a study has shown.

A team of investigators conducted a retrospective target trial emulation using the TriNetX global network to analyse new users of tirzepatide and semaglutide. The primary endpoint was time-to-first MALO (a composite of cirrhosis, decompensated events, and hepatocellular carcinoma). Baseline covariates were balanced via propensity score matching.

The risk of MALO over a median follow-up of about 17 months was not significantly different between tirzepatide and semaglutide initiators (estimated incidence rate [IR], 4.05 vs 4.04 per 1,000 person-year [PY]; hazard ratio [HR], 1.04, 95 percent confidence interval [CI], 0.88‒1.23).

The comparable risk profile persisted across sensitivity analyses, including individuals with metabolic dysfunction-associated liver disease (IR, 9.97 vs 10.03 per 1,000 PY; HR, 1.03, 95 percent CI, 0.75‒1.42) and “as treated” analysis (HR, 0.98, 95 percent CI, 0.80‒1.21). Notably, tirzepatide users achieved greater reduction in BMI (mean difference ~1.1 kg/m2; p<0.001).

“Internal validation confirmed both agents significantly outperformed sitagliptin,” the investigators said.

Obesity 2026;34:1958-1966