New analyses from the ESSENCE phase 3 trial suggest that Novo Nordisk’s Wegovy® (semaglutide 2.4 mg) may benefit liver health in adults with metabolic dysfunction-associated steatohepatitis (MASH) beyond its effects on weight loss.
Presented at the American Association for the Study of Liver Diseases (AASLD) Liver Meeting® 2025 in Washington, D.C., the post hoc analyses evaluated the first 800 randomized patients over 72 weeks. Researchers assessed histological and non-invasive testing (NIT) responses according to weight-loss thresholds (≤2%, ≤5%, ≤7%, >7%).
Results showed improvements in steatohepatitis-related markers across all semaglutide groups, with the strongest reductions in alanine aminotransaminase (ALT) among patients with ≤7% weight loss. In this subgroup, semaglutide recipients experienced a greater mean absolute change in ALT compared with placebo (ETR 0.75, 95% CI 0.68–0.82).
“These data suggest that semaglutide’s effects may not be solely dependent on weight loss and provide important insights into its clinical impact for people living with MASH,” said Professor Philip Newsome, co-chief investigator and director of the Roger Williams Institute of Liver Studies at King’s College Hospital and King’s College London. “These findings deepen our understanding of MASH, which is often accompanied by other systemic conditions, including cardiometabolic disorders.”
Histological endpoints showed similar benefits. Among patients with ≤2% weight loss, 48.4% receiving semaglutide showed improvement in liver injury versus 25.8% on placebo (EDP 21.7, 95% CI 4.9–38.4). Liver scarring also trended favorably: 27.2% versus 18.3% on placebo in this group (EDP 8.3, 95% CI –6.1–22.9).
Dr. Farooq Khan, Consultant Hepatologist at King’s College Hospital Dubai, emphasized the clinical relevance: “Liver disease associated with cardiometabolic health is a significant problem in the GCC, including the UAE. The ESSENCE trial data suggest improvements in liver outcomes beyond weight loss, highlighting the need for early liver disease screening and intervention.”
Further analyses examined efficacy across race, ethnicity, gender, and age. Benefits in liver injury resolution, liver scarring improvement, and related NITs were consistent across these subgroups.
“MASH affects over 250 million people globally and can progress to irreversible liver scarring and failure,” said Martin Holst Lange, Novo Nordisk’s chief scientific officer. “These results indicate that even minimal weight loss with semaglutide 2.4 mg can lead to significant liver health improvements compared to placebo.”
The exploratory analyses are hypothesis-generating, and further research is required to confirm clinical significance. Part 2 of the ESSENCE trial is ongoing, with results expected in 2029.
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