International expert panel review for the use of resmetirom and semaglutide in the management of MASH-related fibrosis: clinical practice update
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.
Authors
- Meena B. Bansal (ORCID: https://orcid.org/0000-0002-7501-2191)
- Philip N. Newsome (ORCID: https://orcid.org/0000-0001-6085-3652)
- Rohit Loomba (ORCID: https://orcid.org/0000-0002-4845-9991)
- Naim Alkhouri (ORCID: https://orcid.org/0000-0001-9872-2391)
- Maria Mironova (ORCID: https://orcid.org/0000-0002-9783-097X)
- Quentin M. Anstee (ORCID: https://orcid.org/0000-0002-9518-0088)
- Vlad Ratziu (ORCID: https://orcid.org/0000-0002-6865-3791)
- Jörn M. Schattenberg (ORCID: https://orcid.org/0000-0002-4224-4703)
- Arun J Sanyal
- Mazen Noureddin
- Mary E Rinella
Institutions
- Inserm (FR)
- King's College - North Carolina (US)
- Virginia Commonwealth University (US)
- University of California San Diego (US)
- University of Chicago (US)
- Centre de Recherche des Cordeliers (FR)
- Methodist Hospital (US)
- Pinnacle Clinical Research (US)
- Newcastle upon Tyne Hospital (GB)
- Ohio Aerospace Institute (US)
- NIHR Newcastle Biomedical Research Centre (GB)
- Newcastle University (GB)
- Saarland University (DE)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- Gut
- Published
- 2026-09-11
- DOI
- https://doi.org/10.1136/gutjnl-2026-340031
- Primary Topic
- Liver Disease Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Gilead Sciences
- Innovative Health Initiative
- Madrigal Pharmaceuticals
- National Institute for Health and Care Research
- Siemens
- National Institute on Alcohol Abuse and Alcoholism
- National Heart, Lung, and Blood Institute
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Center for Advancing Translational Sciences
- HORIZON EUROPE Global Challenges and European Industrial Competitiveness