Resmetirom: An Update on Therapy for Metabolic Dysfunction-Associated Steatohepatitis (MASH)

Abstract: Metabolic dysfunction associated steatotic liver disease (MASLD) affects nearly one-third of adults worldwide, particularly among individuals with obesity or type 2 diabetes, and in 10– 30% progresses to metabolic dysfunction associated steatohepatitis (MASH) or fibrosis. Resmetirom, a selective thyroid hormone receptor-β (THR-β) agonist, became the first therapy to demonstrate both MASH resolution and fibrosis improvement, leading to accelerated food and drug administration (FDA) approval in 2024 and conditional European Medicine Agency (EMA) approval in 2025 in the treatment of fibrotic MASH. Resmetirom is a liver-specific drug that simulates the effect of T3 and thereby reduces intrahepatic fat. It is safe and generally well tolerated. Current clinical guidance recommends treating patients with non-cirrhotic fibrotic MASH (typically those with LSM-VCTE 10– 20 kPa or MRE 3.1– 4.4 kPa), while excluding patients with cirrhosis, active liver disease, significant alcohol use, or untreated thyroid disorders. Treatment monitoring focuses on hepatic safety, thyroid function in selected patients, and assessment of response using non-invasive tests and ALT after 6– 12 months. Real-world data indicate rapid adoption of non-invasive eligibility assessments, early improvements in liver stiffness, and frequent concomitant GLP-1 receptor agonist use, with treatment response appearing independent of weight-loss therapy. As semaglutide has now also gained regulatory approval for fibrotic MASH, optimal positioning of resmetirom within treatment algorithms, combination strategies with GLP-1 receptor agonists, and the long-term impact on liver-related and cardiometabolic outcomes remain key priorities. This review discusses the evidence supporting conditional approval of resmetirom, outlines current clinical recommendations, early real-world experiences, and highlights ongoing challenges and future directions in the management of fibrotic MASH. Keywords: resmetirom, MASLD, MASH, fibrosis, pharmaceutical treatment