Resmetirom or semaglutide for MASH? New guidance helps clinicians choose

Clinical takeaway: For adults with noncirrhotic MASH and stage 2-3 fibrosis, the new EASL-EASD-EASO guidance recommends considering either semaglutide or resmetirom alongside lifestyle intervention. Drug choice should be driven by the patient's cardiometabolic profile, with semaglutide generally favored for obesity, type 2 diabetes, cardiovascular disease, or chronic kidney disease, and resmetirom considered for patients without obesity or those unable to take GLP-1 receptor agonists.

The first joint guidance from the European liver, diabetes, and obesity societies provides practical recommendations for using the newly approved MASH therapies semaglutide 2.4 mg weekly and resmetirom 80-100 mg daily. The document updates the 2024 MASLD guideline to address patient selection, safety monitoring, and treatment follow-up.

A major shift is the recommendation to rely primarily on noninvasive fibrosis tests rather than liver biopsy when determining treatment eligibility. Adults with MASH and fibrosis stage 2-3 identified by elastography, enhanced liver fibrosis (ELF) testing, or biopsy may be candidates for treatment, provided cirrhosis has been excluded.

The guidance emphasizes tailoring therapy to comorbidities. Semaglutide may be prioritized for patients with overweight or obesity, inadequately controlled type 2 diabetes, established cardiovascular disease, or chronic kidney disease because of its weight-loss and cardiometabolic benefits. Resmetirom may be preferred in patients without obesity, those already receiving a GLP-1 receptor agonist, or those with prominent atherogenic dyslipidemia or a preference for oral therapy.

The document also highlights important safety considerations. Clinicians starting semaglutide should assess risks such as pancreatitis, gallbladder disease, diabetic eye disease, and sarcopenia, while resmetirom requires review of thyroid function and potential drug interactions, including with statins and clopidogrel.

Regular monitoring is advised after treatment initiation. Noninvasive fibrosis assessments should be used to evaluate hepatic response, while patients receiving semaglutide may benefit from ongoing nutritional assessment because substantial weight loss can be accompanied by loss of muscle mass.

The guidance notes that semaglutide and resmetirom appear reasonably safe in compensated cirrhosis, but neither should currently be used as MASH-targeted therapy in cirrhotic patients until outcome data become available.

“Treatment selection should be individualised according to preferences, potential risks, and cardio-renal-metabolic profile,” the authors wrote, underscoring a move away from a one-size-fits-all approach to MASH treatment.

What's changed

• New practical guidance for use of approved MASH-targeted drugs semaglutide and resmetirom.
• Noninvasive fibrosis testing is preferred over routine liver biopsy for treatment selection.
• Semaglutide is favored in obesity, type 2 diabetes, cardiovascular disease, and chronic kidney disease.
• Resmetirom is favored in patients without obesity, those already on or intolerant of GLP-1 therapy, and those with significant dyslipidemia.
• Combination therapy with semaglutide plus resmetirom cannot yet be recommended as first-line treatment because evidence is lacking.

Source: European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), European Association for the Study of Obesity (EASO). (2026 Sep 28) J Hepatol. EASL-EASD-EASO guidance on the use of resmetirom and semaglutide as MASH-targeted therapy