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Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis.

Phase 3 Randomized Controlled TrialStrong evidence

This record provides bibliographic details and links to the original research. An editorial study breakdown is not available.

What the researchers found

Semaglutide 2.4 mg resolved MASH in 62.9% of patients versus 34.3% with placebo, and reduced liver fibrosis in 36.8% versus 22.4%, at the 72-week interim analysis.

Why it matters

MASH (fatty liver disease with inflammation and scarring) has no widely approved drug treatment. This landmark NEJM trial positions semaglutide as a potential first-line therapy for a disease affecting millions.

The numbers in context

n=1,197 (2:1 randomization); MASH resolution: 62.9% vs 34.3% (diff 28.7%, p<0.001); fibrosis reduction: 36.8% vs 22.4% (diff 14.4%, p<0.001); combined: 32.7% vs 16.1% (p<0.001); weight: -10.5% vs -2.0% (p<0.001)

How the study worked

Phase 3, multicenter, randomized, double-blind, placebo-controlled trial. Patients with biopsy-confirmed MASH and fibrosis stage 2-3. Weekly SC semaglutide 2.4 mg vs placebo for 240 weeks. Interim analysis at 72 weeks (first 800 patients). Primary endpoints: MASH resolution without fibrosis worsening; fibrosis improvement without MASH worsening.

Who was studied

Adults with biopsy-confirmed MASH and liver fibrosis stage 2 or 3

What this study cannot tell us

Interim analysis; full trial (240 weeks) still ongoing. GI adverse events common with semaglutide. Pain scores did not improve. Long-term durability and effect on liver-related clinical events unknown.

Read the original research

Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis.

The New England journal of medicine, 392(21), 2089-2099

Citation

Sanyal, Arun J; Newsome, Philip N; Kliers, Iris; Østergaard, Laura Harms; Long, Michelle T; Kjær, Mette Skalshøi; Cali, Anna M G; Bugianesi, Elisabetta; Rinella, Mary E; Roden, Michael; Ratziu, Vlad. (2025). Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis.. The New England journal of medicine, 392(21), 2089-2099. https://doi.org/10.1056/NEJMoa2413258