Resmetirom for MASH: A Comprehensive Review of a Novel Therapeutic Frontier

Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease linked to type 2 diabetes (T2D), obesity, and dyslipidaemia, which are all parts of the metabolic syndrome. In 2024, for non-cirrhotic MASH with mild to advanced fibrosis, resmetirom, a selective thyroid hormone receptor-β agonist, became the first FDA-approved treatment for this condition. By increasing β-oxidation and lipid metabolism, it minimises systemic thyroid or cardiac effects while reducing hepatic fat, inflammation, and fibrosis. Resmetirom is being developed for use in combination with lifestyle interventions, such as diet and exercise, to maximize patient benefit. Nevertheless, the lack of congruence between clinical trial populations and real-world payer criteria underscores access obstacles that necessitate policy reform. The successful delivery of screening programs depends on the education of providers from various disciplines and the establishment of uniform screening standards. Future studies should investigate the clinical application of resmetirom in combination with agents that may provide additional benefits, such as GLP-1 receptor agonists, SGLT2 inhibitors, and statins. These results are significant in light of recent long-term safety monitoring of these agents, particularly regarding the thyroid axis. Ensuring equitable uptake will be crucial, as it involves defining fair access through payer endpoints, conducting cost-effectiveness analysis, and considering patient-reported outcomes. Resmetirom represents a breakthrough in MASH management, offering potential metabolic benefits in conjunction with comprehensive clinical and lifestyle approaches.