Fibroblast growth factor 21, the endocrine FGF pathway and novel treatments for metabolic syndrome

Diabetes and associated metabolic conditions have reached pandemic proportions worldwide, and there is a clear unmet medical need for effective and safe therapies. Fibroblast growth factor (FGF)21 is an atypical member of the FGF family. The ability of FGF21 to normalize glucose, lipid and energy homeostasis has attracted considerable interest as a potential therapeutic for treating diabetes and obesity. Many different engineering approaches have successfully improved the plasma half life, protein stability and solubility, as well as 'manufacturability' of FGF21. Novel approaches such as agonist antibodies to FGF21 receptor complexes have opened new opportunities previously unavailable. This review summarizes recent advances in understanding the functions, target tissues and receptors for FGF21. Furthermore, it provides an up-to-date appraisal of the approaches on therapeutic development targeting this pathway.