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

Sanyal, Arun J et al.·The New England journal of medicine·2025·Strong Evidencephase 3 randomized controlled trial
RPEP-13417Phase 3 randomized controlled trialStrong Evidence2025RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
phase 3 randomized controlled trial
Evidence
Strong Evidence
Sample
N=1,197 (800 in interim analysis)
Participants
Adults with biopsy-confirmed MASH and liver fibrosis stage 2 or 3

What This Study 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.

Key Numbers

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 They Did This

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.

Why This Research 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.

What This Study Doesn't 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.

Trust & Context

Original Title:
Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis.
Published In:
The New England journal of medicine, 392(21), 2089-2099 (2025)
Database ID:
RPEP-13417

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled Trial
Cohort / Case-Control
Cross-Sectional / ObservationalSnapshot without intervening
This study
Case Report / Animal Study
What do these levels mean? →

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Cite This Study

RPEP-13417·https://rethinkpeptides.com/research/RPEP-13417

APA

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

MLA

Sanyal, Arun J, et al. "Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis.." The New England journal of medicine, 2025. https://doi.org/10.1056/NEJMoa2413258

RethinkPeptides

RethinkPeptides Research Database. "Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associ..." RPEP-13417. Retrieved from https://rethinkpeptides.com/research/sanyal-2025-phase-3-trial-of

Access the Original Study

Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.

This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.