Resmetirom: An Innovative Treatment for Steatohepatitis Associated with Metabolic Dysfunction (MASH)

Abstract

A progressive optional of metabolic dysfunction–associated steatotic liver disease (MASLD), metabolic dysfunction–associated steatohepatitis (MASH), formerly known as nonalcoholic steatohepatitis (NASH), can develop to cirrhosis, fibrosis, and hepatocellular cancer. Until recently, treatment strategies were limited to lifestyle modification and off-label pharmacological approaches with modest efficacy. A selective thyroid hormone receptor-β (THR-β) agonist called Resmetirom (MGL-3196) is the first FDA-approved medication for non-cirrhotic MASH with moderate-to-advanced fibrosis. This review summarizes the pharmacological basis, mechanism of action, preclinical findings, and clinical trial outcomes of resmetirom across Phase I–III studies. Resmetirom demonstrates potent hepatic fat reduction, improvement in histological endpoints, and favorable modulation of atherogenic lipid markers, with a consistent safety profile predominantly characterized by mild gastrointestinal adverse effects. When compared with other emerging therapeutic classes such as FXR agonists, PPAR agonists, and GLP-1 receptor agonists, resmetirom offers a unique dual benefit by targeting both hepatic pathology and cardiometabolic risk. Its regulatory approval in 2024 marks a paradigm shift in MASH management, although long-term outcome data, accessibility challenges, and combination therapy strategies remain areas of active investigation. Overall, resmetirom stands as a transformative agent with the potential to redefine the therapeutic landscape of MASH.