FGF21 analogues

FGF21 analogues

Fibroblast growth factor 21 (FGF21), a pleiotropic hormone secreted mainly by the liver, regulates glucose and lipid metabolism and insulin sensitivity (1). Elevated levels of FGF21 are associated with metabolic diseases, including obesity, lipodystrophy, diabetes, and metabolic dysfunction-associated steatotic liver disease (MASLD) (1). Preclinical data suggest that in the liver, FGF21 stimulates fatty acid oxidation and decreases lipogenesis to lessen new TG accumulation, and promotes TG secretion as very-low-density lipoprotein (VLDL) to reduce existing fat stores (2). In adipose tissue, FGF21 improves insulin sensitivity and accelerates TG-rich lipoprotein turnover (2).

Pegozafermin

Pegozafermin is a glycopegylated recombinant analogue of human FGF21 that is being developed for the treatment of severe hypertriglyceridaemia and nonalcoholic steatohepatitis (NASH)/MASLD (2). In a Phase 1b/2a ascending dose study in patients with NASH/MASLD, pegozafermin was generally well tolerated and associated with clinically meaningful reductions in liver fat, measures of liver function, and circulating lipids (3).

DR10624

DR10624 is a triple agonist of FGF21, glucagon and GLP-1 which are involved in lipid and glucose metabolism. In a Phase 1b/2a study, in obese participants with moderate hypertriglyceridaemia, DR10624 administered weekly for 12 weeks significantly reduced TG and liver fat, and improved insulin sensitivity, with a good tolerability and safety profile (4).