Current status and future perspectives of FGF21 analogues in clinical trials

Abstract

Recent advances in fibroblast growth factor 21 (FGF21) biology and pharmacology have led to the development of several long-acting FGF21 analogues and antibody-based mimetics now in various phases of clinical trials for the treatment of obesity-related metabolic comorbidities. The efficacy of these FGF21 analogues/mimetics on glycaemic control and weight loss is rather mild and inconsistent; nevertheless, several promising therapeutic benefits have been reproducibly observed in most clinical studies, including amelioration of dyslipidaemia (particularly hypertriglyceridaemia) and hepatic steatosis, reduction of biomarkers of liver fibrosis and injury, and resolution of metabolic dysfunction-associated steatohepatitis (MASH). Evidence is emerging that combination therapy with FGF21 analogues and other hormones (such as glucagon-like peptide 1; GLP-1) can synergise their pharmacological benefits, thus maximising the therapeutic efficacy for obesity and its comorbidities.