Comparative anti-fibrotic efficacy of resmetirom, semaglutide, tirzepatide and efruxifermin in the GAN diet-induced obese and biopsy-confirmed mouse model of MASH

Background & aim:

Resmetirom (RES, THR-βR agonist) has recently been FDA-approved for the treatment of metabolic dysfunction-associated steatohepatitis (MASH). Other drug concepts are in late-stage clinical development for MASH, including semaglutide (SEMA, GLP1R agonist), tirzepatide (TZP, GLP1R-GIPR co-agonist) and efruxifermin (EFX, FGF21 analogue). The present study aimed to compare the efficacy of RES, SEMA, TZP and EFX monotherapy on metabolic, biochemical and histopathological outcomes in the translational Gubra Amylin NASH (GAN) diet-induced obese and biopsy-confirmed mouse model of MASH with moderate/advanced liver fibrosis.