FGF21 Analogues and MASLD: A Summary of Preclinical and Clinical Data

Abstract: Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD) is the most frequent chronic liver disease, which is closely associated with metabolic syndrome and obesity. Although it has now reached epidemic proportions, the treatment of this disease remains a challenge. Currently, there is only one drug approved for metabolic dysfunction-associated steatohepatitis (MASH), and various pharmaceutical agents have reached phase 3 of clinical trials and appear as potential drugs for the disease. Fibroblast Growth Factor (FGF) 21 has been gaining increasing interest as a possible therapeutic target for MASLD. FGF21 analogues, with an improved pharmacodynamic and pharmacokinetic profile, exert pleiotropic, favorable effects on liver function and histology, as well as systemic metabolism. They also appear to be effective in alleviating hepatic steatosis, steatohepatitis, and fibrosis in MASH. Among various others, efruxifermin, pegozafermin, pegbelfermin, and BOS-580 are FGF-21 analogues that have resulted in significant improvements in liver fat, fibrosis, and measures of liver function in the context of phase 2 clinical trials. This review summarizes the preclinical and clinical data from FGF21 analogues for MASLD and MASH.