European Guidance Outlines Resmetirom and Semaglutide Use in Noncirrhotic MASH

The European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), and European Association for the Study of Obesity (EASO) have issued joint guidance in the Journal of Hepatology on the use of resmetirom (Rezdiffra, Madrigal Pharmaceuticals) and semaglutide as metabolic dysfunction-associated steatohepatitis (MASH)-targeted therapy.

The guidance, which followed regulatory approvals of both agents, covers candidate selection, treatment initiation, monitoring, and discontinuation. Recommendations were graded using the Oxford Centre for Evidence-Based Medicine system and finalized through a Delphi process.

According to the guidance, adults with noncirrhotic MASH and stage 2 to 3 fibrosis should be considered for resmetirom (80mg or 100mg orally daily) or semaglutide (2.4mg subcutaneously weekly) in addition to, not instead of, lifestyle modification. The authors said noninvasive tests should be preferred over liver biopsy for identifying candidates, citing thresholds including vibration-controlled transient elastography of 10 to 20 kPa, magnetic resonance elastography of 3.1 to 5.0 kPa, or an enhanced liver fibrosis score of 9.8 to 11.3.

The guidance states that drug choice should be individualized. Semaglutide may be prioritized in patients with obesity or overweight with weight-related comorbidities, type 2 diabetes outside glycemic targets, established cardiovascular disease, or chronic kidney disease with overweight/obesity and/or type 2 diabetes. Resmetirom may be prioritized in those without obesity and type 2 diabetes, or when a glucagon-like peptide-1 receptor agonist is already used for another indication or is not tolerated. The authors noted that the registrational phase 3 trials were not head-to-head, so direct efficacy comparison is not possible.

Neither agent should be used as MASH-targeted treatment in patients with cirrhosis until further data become available, according to the guidance. The authors said ongoing studies are evaluating the long-term effectiveness of both agents in reducing major adverse liver-related outcomes.

Source: Tacke F, Horn P, Wong VWS, et al. EASL-EASD-EASO guidance on the use of resmetirom and semaglutide as MASH-targeted therapy. J Hepatol. Published online September 28, 2026. doi:10.1016/j.jhep.2026.08.028