1776-P: Early Real-World Liver Biomarker Changes among Resmetirom-Treated MASH Patients, with and without Concomitant GLP-1 Use: A Descriptive Cohort Study

Introduction and Objective: Resmetirom, a THR-β agonist, and semaglutide, a GLP-1 agonist, are conditionally FDA-approved for noncirrhotic MASH with moderate-to-advanced fibrosis. We descriptively assessed early mean changes in liver and metabolic biomarkers with resmetirom and by concomitant GLP-1 use during follow-up. Methods: A descriptive, retrospective cohort study using Latica real-world data repository included adults with ≥1 resmetirom prescription (Apr 2024-2025; index date = first prescription) and ≥6 months follow-up, excluding those with end-stage liver disease in the 2 years prior to index. Patients were stratified by GLP-1 use during follow-up. Outcomes included mean changes in liver enzymes, metabolic measures, and non-invasive fibrosis markers (FAST score, Liver Stiffness Measurement [LSM] and Controlled Attenuation Parameter [CAP]). Responder endpoints were defined as FAST reduction ≥0.22, ALT reduction ≥17 U/L or ≥20%, and LSM reduction ≥30%. Results: The cohort included 712 patients; 139 (19.5%) had concomitant GLP-1 use during follow-up (of whom 95 [68.3%] used GLP-1 pre-index). All GLP-1 users had T2DM; among resmetirom users without GLP-1, 272 (47.5%) had T2DM. Obesity was frequent in both groups (86.3% with GLP-1 vs 67.5% without). Biomarker reductions were similar with and without GLP-1 use, respectively (ALT −14.2 U/L [n=79] vs −13.4 [n=251]; AST −8.2 [n=78] vs −8.6 U/L [n=244]; BMI −0.9 vs −0.6 kg/m² [n=132 vs 371]). Higher improvements in LSM were seen among concomitant users (LSM −3.2 vs −1.9 kPa [n=20 vs 50]), however CAP reductions were greater without GLP-1 (−39.5 vs −43.9 dB/m [n=13 vs 32]). Responder rates (%) were broadly comparable between patients with and without GLP-1 for LSM (40.0 vs 42.0) and ALT (48.1 vs 46.2), but higher for FAST (50.0 vs 40.0). Conclusion: These early descriptive results demonstrate mean improvements in liver biomarkers among resmetirom users with and without GLP-1 concomitant use; larger studies with longer follow-up are needed to confirm these findings. Disclosure Y. Kim: Employee; Current; Madrigal Pharmaceuticals, Inc. Stock/Shareholder; Current; Madrigal Pharmaceuticals, Inc. N. Alkhouri: Advisory Panel; Current; Madrigal Pharmaceuticals, Inc. Speaker's Bureau; Current; Madrigal Pharmaceuticals, Inc. Research Support; Current; Madrigal Pharmaceuticals, Inc. Advisory Panel; Current; Novo Nordisk. Speaker's Bureau; Current; Novo Nordisk. Research Support; Current; Novo Nordisk. J. O'Donnell: Employee; Current; Madrigal Pharmaceuticals, Inc. Stock/Shareholder; Current; Madrigal Pharmaceuticals, Inc. K.M. Johnston: None. R. Mustafa: None. Y. Silberberg: Other - Employees of Latica, which received funds from Madrigal Pharmaceuticals for this work.; Current; Madrigal Pharmaceuticals, Inc.