FGF21 Revolutions: Recent Advances Illuminating FGF21 Biology and Medicinal Properties

The biology of fibroblast growth factor 21 (FGF21) has evolved through its first decade at a revolutionary pace with dramatic refinements in this relatively short span of time. This field is poised now with a deeper understanding of its specific physiological role, pathological ramifications for its inappropriate function, and a much-enriched context of the complex hormonal network in which it serves to regulate metabolism. As a derivative of these discoveries, the application of FGF21 as a medicinal agent has emerged with structurally optimized protein-based analogs being preclinically explored in multiple species, and, more recently, through clinical studies. These novel findings set a foundation for ongoing inquiries that structure future research into this intriguing protein.

TrendsFibroblast Growth Factor 21 (FGF21) is a novel protein and a target for the development of novel medicines for metabolic diseases.FGF21 is an integral part of a hormonal network that controls metabolism and includes insulin, leptin, glucagon-like peptide, adiponectin, growth hormone, Glucagon-like Peptide 1 (GLP1), and Insulin-like growth factor 1 (IGF1).In animal models, FGF21 delivers impressive pharmacological effects that correct multiple abnormalities of the metabolic syndrome some of which are recapitulated in patients with diabetes.Two recent clinical trials in diabetes demonstrated that FGF21 agonism was well tolerated, and rapidly minimized dyslipidemia, with progressive lowering of body weight.