Fibroblast Growth Factors 19 and 21 (FGF19 and FGF21) are novel endocrine messengers that regulate multiple aspects of energy homeostasis. The magnitude and pleotropic character of their beneficial actions on many, if not all abnormalities of the metabolic syndrome in animals led to extensive exploration of their biology and coordinated efforts to design novel FGF19/21-based analogs for therapeutic purposes. While initial attempts to develop such medicines were primarily focused on improving hyperglycemia in type 2 diabetes patients, the robust, consistent and durable effects on lipid metabolism in human trials gradually transformed clinical emphasis for these factors toward their use for non-alcoholic steatohepatitis (NASH) and severe hypertriglyceridemia (SHTG). In this review, we will communicate an overview of FGF19 and FGF21 biology and the basic mechanisms of their action, that will be followed by in-depth analysis of the recent developments with FGF21/19-based analogs in the clinic.

Keywords: FGF19; FGF21; NASH; clinical trials; drug development; metabolism.