A WEEKLY injection of efinopegdutide improved liver biopsy outcomes in adults with metabolic dysfunction-associated steatohepatitis (MASH) and moderate-to-advanced fibrosis, according to phase 2b trial results.
The investigational treatment increased the proportion achieving MASH resolution without worsening fibrosis compared with placebo. The findings offer a clinical development in a disease where inflammation and scarring can progress together, although longer-term benefits remain to be established.
The randomised trial compared efinopegdutide doses of 4 mg, 7 mg and 10 mg with placebo over 52 weeks. It also included an open-label semaglutide 2.4 mg reference arm. Efinopegdutide and placebo were assessed under blinded conditions, while participants receiving semaglutide knew their treatment allocation.
Overall, 381 adults received at least one dose. Participants had biopsy-confirmed MASH and stage F2 or F3 fibrosis. Efinopegdutide targets both GLP-1 and glucagon receptors.
At week 52, MASH resolution without worsening fibrosis occurred in 56%, 63% and 61% of participants receiving the three ascending efinopegdutide doses, respectively, compared with 13% receiving placebo. All three comparisons met statistical significance.
Fibrosis improvement of at least one stage without worsening steatohepatitis occurred in 43%, 52% and 34%, respectively, versus 21% with placebo. The 7 mg group therefore had the highest numerical response on both reported biopsy endpoints.
These endpoints address different aspects of liver disease. Resolution of steatohepatitis concerns inflammatory disease activity, whereas fibrosis improvement concerns the extent of scarring. Improvement in one does not automatically establish improvement in the other, making their separate assessment important.
Gastrointestinal adverse effects were common. Treatment discontinuation because of adverse events occurred in 3%, 4% and 11% of the ascending-dose groups, compared with 1% on placebo.
The results highlight why dose selection requires consideration of tolerability alongside response rates. A higher dose should not be assumed to offer the best balance for patients simply because it delivers more medication.
The trial was sponsored by Merck Sharp & Dohme. Efinopegdutide remains investigational, and these findings do not establish reductions in liver failure, transplantation or mortality. Nor does the presence of an open-label semaglutide reference arm, by itself, establish superiority over that treatment.
Further trials will be needed to clarify durability, safety and clinical outcomes. For now, the findings support continued investigation of efinopegdutide as a potential treatment for MASH with fibrosis.
Reference
Lawitz E et al. Efficacy and safety of efinopegdutide in adults with metabolic dysfunction-associated steatohepatitis and stage 2–3 fibrosis: a phase 2b, randomised, placebo-controlled study. The Lancet. Published online 9 November 2026. doi:10.1016/S0140-6736(26)02043-X.
Feature image: Dasha Petrenko on AdobeStock
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