FGF21 agonists: An emerging therapeutic for metabolic dysfunction-associated steatohepatitis and beyond

The worldwide epidemics of obesity, hypertriglyceridemia, dyslipidemia, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease (MASLD) / metabolic dysfunction-associated steatohepatitis (MASH) represents a major economic burden on healthcare systems. At-risk MASH patients, defined as MASH with moderate or significant fibrosis are at higher risk of comorbidity / mortality with a significant risk of cardiovascular diseases and/or major adverse liver outcomes. Despite a high unmet medical need, there is no approved therapy to date. Several drug candidates have reached the phase 3 development stage and could lead to several potential conditional drug approvals in the coming years. Within the armamentarium of future treatment options, FGF21 analogs exhibit an interesting positioning thanks to their pleiotropic effects in addition to their significant effect on both MASH resolution and fibrosis improvement. In this review, we summarize preclinical and clinical data from FGF21 analogs for MASH and explore additional potential therapeutic indications.