Selecting Pharmacologic Interventions for MASH

Metabolic dysfunction-associated steatohepatitis (MASH) is now recognized as the leading cause of cirrhosis, an important risk factor for hepatocellular carcinoma, and a growing indication for liver transplantation. The U.S. Food and Drug Administration has recently approved two agents for the treatment of MASH in adults who have progressed to moderate-to-advanced hepatic fibrosis: resmetirom and semaglutide. Resmetirom is an oral, once-daily selective thyroid hormone receptor-β agonist that reduces steatohepatitis, promotes fibrosis regression, and improves atherogenic lipid particles. Semaglutide, a once-weekly subcutaneous glucagon-like peptide-1 receptor agonist, was originally approved for diabetes but has also demonstrated efficacy in treating MASH and hepatic fibrosis, while also exerting favorable effects on cardiometabolic risk profiles. As both agents are now considered first-line, clinicians face the challenge of selecting the optimal treatment. This review analyzes the pivotal data from the MAESTRO-NASH and ESSENCE trials to compare their contraindications, side effects, and clinical benefits, providing a practical framework for individualizing MASH treatment.