Metabolic HealthMASH Treatment Revolution: Semaglutide, Tirzepatide Lead a New Drug Era
Metabolic dysfunction-associated steatohepatitis (MASH) is now a leading cause of liver disease globally, driven by obesity and type 2 diabetes. This major review in the Journal of Clinical Investigation synthesizes the latest pharmacological advances, covering GLP-1 agonists like semaglutide, dual agonists like tirzepatide and survodutide, metabolic modulators including resmetirom, lanifibranor, and pegozafermin, and emerging targets like fatty acid synthase inhibitors. Phase II and III trial data show MASH resolution rates of 46–63% with newer agents versus 11–34% with placebo. The review also addresses unresolved challenges: treatment duration, weight regain after stopping therapy, adherence, genetic response heterogeneity, and risks in patients with advanced fibrosis or cirrhosis.
