MASH Pharmacotherapy Enters Clinical Practice: Resmetirom or Semaglutide—Who Gets What?: Gut | September 2026
What Does This Update Add?
With resmetirom and semaglutide now available for non-cirrhotic MASH with significant F2–F3 fibrosis, this international expert panel provides a practical framework for moving from trial evidence to real-world treatment.
- Treatment is directed toward patients with MASH-related significant fibrosis (F2–F3) without cirrhosis.
- Resmetirom is a liver-directed thyroid hormone receptor-β agonist targeting hepatic fat metabolism and fibrosis-related disease activity.
- Semaglutide offers broader metabolic benefits through GLP-1 receptor agonism, particularly relevant when obesity and metabolic disease coexist.
- The panel emphasizes non-invasive test-based identification of appropriate treatment candidates rather than requiring routine liver biopsy for every patient.
- Treatment choice should be phenotype-driven, integrating liver fibrosis risk with obesity, diabetes, cardiovascular/metabolic disease and treatment priorities.
- Patients already receiving a GLP-1 RA require a specific assessment before changing or adding MASH-directed therapy.
- Monitoring should evaluate both liver response and metabolic response, rather than weight loss or liver enzymes alone.
- The update proposes practical definitions of response and non-response, with consideration of switching therapy when treatment goals are not achieved.
- Combination therapy with agents targeting complementary pathways is discussed as an emerging strategy, but evidence remains incomplete.
- Patients with cirrhosis are outside the current treatment population addressed by these approvals.
Why Does It Matter?
MASH management is shifting from lifestyle intervention and risk-factor control alone to active pharmacological treatment of fibrosis. Clinicians now need to decide not simply whether to treat, but which drug best matches the individual patient's liver and metabolic phenotype.
GastroAGI Takeaway
MASH treatment is becoming phenotype-based rather than one-drug-fits-all. Resmetirom offers a predominantly liver-directed strategy, whereas semaglutide combines MASH treatment with powerful weight and metabolic effects. The next evolution will likely involve NIT-guided treatment selection, objective response monitoring and rational combination therapy—while avoiding extrapolation to cirrhosis until appropriate evidence is available.
