Resmetirom and Semaglutide: Comparing Efficacy, Safety, and Selection for MASH with Fibrosis

Metabolic dysfunction-associated steatohepatitis (MASH) is now the leading cause of cirrhosis, a significant risk factor for hepatocellular carcinoma, and a growing indication for liver transplantation. Despite its prevalence, effective pharmacological therapies have historically been limited. The recent FDA approvals of resmetirom and semaglutide for adults with moderate-to-advanced hepatic fibrosis represent a critical advancement. Clinicians now face the challenge of selecting the optimal first-line agent, necessitating a clear understanding of their comparative profiles.

This review analyzed pivotal data from the MAESTRO-NASH and ESSENCE trials to compare the two recently FDA-approved agents for MASH. The authors specifically examined resmetirom (an oral, once-daily selective thyroid hormone receptor-β agonist) and semaglutide (a once-weekly subcutaneous glucagon-like peptide-1 receptor agonist). The study systematically compared their respective contraindications, side effects, and clinical benefits, with the aim of providing a practical framework for individualizing MASH treatment selection in adults who have progressed to moderate-to-advanced hepatic fibrosis.

The review highlights that resmetirom, a selective thyroid hormone receptor-β agonist, effectively reduces steatohepatitis and promotes fibrosis regression. Furthermore, resmetirom demonstrated improvements in atherogenic lipid particles, addressing a key comorbidity in MASH patients. Semaglutide, a GLP-1 receptor agonist, originally approved for diabetes, also showed significant efficacy in treating MASH and hepatic fibrosis. > The review emphasizes that semaglutide concurrently exerts favorable effects on cardiometabolic risk profiles, offering a broader benefit beyond liver-specific outcomes. Both agents are now considered first-line treatments for MASH in adults with moderate-to-advanced hepatic fibrosis, necessitating a nuanced approach to patient selection based on their distinct mechanisms, side effect profiles, and broader cardiometabolic impacts.