Cell Rep Med. 2026 Sep 4:103023. doi: 10.1016/j.xcrm.2026.103023. Online ahead of print.
ABSTRACT
Recent therapeutic advances have resulted in US Food and Drug Administration (FDA) approval of the first pharmacological agents-resmetirom and semaglutide-for advanced metabolic dysfunction-associated steatohepatitis (MASH) without cirrhosis, reshaping the therapeutic landscape of the disease. Within this evolving framework, incretin-based pharmacotherapies-including glucagon-like peptide-1 (GLP-1) receptor agonists and their dual and triple combinations with glucose-dependent insulinotropic peptide (GIP) and/or glucagon receptor agonists-have emerged as promising options, particularly for individuals with coexisting obesity or type 2 diabetes. These agents exert pleiotropic effects across multiple organs, modulating glucose and lipid metabolism, while providing cardiovascular and renal benefits. Despite these advances, key challenges remain regarding treatment duration, tolerability, and interindividual variability in therapeutic response. This review summarizes the emerging role of GLP-1 mono, dual, and triple agonists in MASH-related fibrosis, focusing on their mechanisms of action and evidence from phase 2 and phase 3 clinical trials with histology-assessed hepatic endpoints.
PMID:42697203 | DOI:10.1016/j.xcrm.2026.103023