This joint EASL-EASD-EASO guidance evaluates the use of resmetirom (80mg/100mg orally) and semaglutide (2.4mg subcutaneously weekly) as MASH-targeted therapies in adults with non-cirrhotic MASH and fibrosis stages 2–3, covering patient selection, treatment initiation, monitoring, and discontinuation.
Both agents are recommended for adults with non-cirrhotic MASH (fibrosis F2–F3) alongside lifestyle intervention; semaglutide is preferred when obesity, type 2 diabetes, or established cardiovascular disease is present, while resmetirom is prioritized in those without obesity or who are already on or intolerant to GLP-1RAs. Neither agent should be used as MASH-targeted therapy in cirrhosis until further data are available.
Recommendations are based on regulatory approval data and expert consensus; long-term effectiveness data reducing major adverse liver-related outcomes (MALO) are still pending from ongoing trials. Evidence supporting use in MASH cirrhosis remains insufficient.
In adults with MASH and fibrosis F2–F3 (confirmed by NITs such as VCTE 10–20 kPa, MRE 3.1–5.0 kPa, or ELF 9.8–11.3, or biopsy), initiate pharmacotherapy alongside lifestyle intervention and optimize comorbidities. Choose semaglutide for patients with obesity, T2D, or high cardiovascular risk, and resmetirom for those without obesity or who cannot tolerate GLP-1RAs; monitor for nutritional status and sarcopenia during semaglutide use.
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