FGF21-based pharmacotherapy - potential utility for metabolic disorders

Currently available therapies for diabetes or obesity produce modest efficacy and are usually used in combination with agents targeting cardiovascular risk factors. Fibroblast growth factor 21 (FGF21) is a circulating protein with pleiotropic metabolic actions; pharmacological doses of FGF21 produce anti-diabetic, lipid-lowering, and weight-reducing effects in rodents. Several potential benefits have translated to non-human primates and obese humans with type 2 diabetes (T2D). Accumulating results point to a specific receptor complex and actions in adipose tissue, liver, and brain; several pathways lead to enhanced fatty acid oxidation, increased insulin sensitivity, and augmented energy expenditure. A range of strategies are being explored to derive potent, safe, and convenient therapies which could potentially represent novel approaches to prevent and treat a variety of metabolic disorders.