GutSep 11, 2026

Expert review on using resmetirom and semaglutide to treat liver scarring from fatty liver disease

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Sep 12, 2026

Abstract

The FDA has conditionally approved two therapies for metabolic dysfunction-associated steatohepatitis (MASH) with significant fibrosis (F2-F3).

Resmetirom and semaglutide represent the first pharmacological treatments for MASH with significant fibrosis.
Resmetirom functions as a liver-directed thyroid hormone receptor-beta agonist, while semaglutide acts as a glucagon-like peptide-1 receptor agonist.
The review consolidates phase III trial data and FDA labels, providing a comprehensive resource for clinicians.
It addresses the entire care pathway, including diagnosis, treatment initiation, and response assessment.
Practical recommendations are offered for individualizing therapy based on patient characteristics and managing existing GLP-1 RA treatments.

Simplified

The recent conditional US Food and Drug Administration (FDA) approval of two therapies, resmetirom (Rezdiffra) and semaglutide (Wegovy), marks the first time clinicians have pharmacological therapy for metabolic dysfunction-associated steatohepatitis (MASH) with significant fibrosis (F2-F3) without cirrhosis, a disease that previously had no available pharmacological treatment. The two agents act through complementary mechanisms: resmetirom as a liver-directed thyroid hormone receptor-beta agonist and semaglutide as a glucagon-like peptide-1 receptor agonist (GLP-1 RA) with a broad spectrum of metabolic effects. In this international expert panel review, we consolidate data from phase III trials, FDA labels and emerging clinical experience into a single resource. It covers the entire care pathway: non-invasive test-based diagnosis of MASH with significant fibrosis, treatment selection and initiation, on-treatment monitoring and response assessment. We offer practical recommendations for individualising therapy by patient phenotype, managing patients already receiving GLP-1 RAs and defining response, non-response and criteria for switching or combining agents. The proposed framework is intended to evolve as long-term outcomes data emerge and additional MASH therapies become available.

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Expert review on using resmetirom and semaglutide to treat liver scarring from fatty liver disease

Abstract

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