Semaglutide May Improve Liver Outcomes, Regardless of Weight Loss Effects in MASH: Daily Dose

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On November 12, 2025, we reported on a study presented at The Liver Meeting® 2025 of the American Association for the Study of Liver Diseases (AASLD) that examined the efficacy of semaglutide 2.4 mg (Wegovy^®) in persons with metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis stage 2 or 3.

The study

Researchers conducted a post hoc analysis of the phase 3 ESSENCE clinical trial. A total of 800 participants were randomly assigned to receive weekly subcutaneous semaglutide 2.4 mg or placebo.

At baseline and week 72, participants underwent liver biopsy and noninvasive tests (NITs). For the purpose of the study, treatment response was defined as at least a 17-unit reduction in alanine transaminase (ALT) and at least a 0.22 reduction in FibroScan-AST (FAST) score for MASH, 30% reduction in vibration controlled transient elastography (VCTE) and at least a 0.5-unit reduction in Enhanced Liver Fibrosis (ELF) score, and MASH resolution and fibrosis improvement for histology.

The findings

Steatohepatitis-related NITs improved in all semaglutide groups, with the greatest treatment effect observed in ALT levels among patients who lost ≤7% of body weight. In this subgroup, the mean absolute change in ALT from baseline to week 72 favored semaglutide versus placebo (estimated treatment ratio [ETR] 0.75; 95% CI, 0.68–0.82).

For histological outcomes, semaglutide 2.4 mg was associated with resolution of liver injury at all weight loss thresholds. Among participants with ≤2% weight loss, 48.4% of those receiving semaglutide achieved resolution of liver injury compared with 25.8% of those on placebo (estimated difference in responder proportions [EDP] 21.7; 95% CI, 4.9–38.4). Improvements in liver scarring also trended in favor of semaglutide across all groups; in the ≤2% weight loss subgroup, improvement occurred in 27.2% of the semaglutide group versus 18.3% of the placebo group (EDP 8.3; 95% CI, –6.1 to 22.9).

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