Semaglutide and Resmetirom in Patients With Metabolic Dysfunction-Associated Steatohepatitis and Fibrosis: An Exploratory Indirect Comparison

this exploratory indirect comparison suggests that semaglutide 2.4 mg/week may confer slightly greater efficacy in achieving MASH resolution without worsening fibrosis than resmetirom (especially at 80 mg/day). Anti-fibrotic hepatic effects appear broadly comparable between semaglutide 2.4 mg/week and resmetirom across both daily doses. We believe semaglutide should be prioritized to achieve sustained improvement in the systemic drivers of MASH, particularly in patients with obesity and/or type 2 diabetes. Conversely, resmetirom is best suited for patients with advanced fibrosis or an incomplete metabolic response, with combination strategies increasingly justified to target both systemic drivers and intrahepatic injury pathways. However, head-to-head comparative and combination trials are required to define optimal therapeutic strategies for MASH and moderate-to-advanced fibrosis.