Recent publications on Residual Risk

Fibroblast growth factor 21 (FGF21) is a key mediator of fatty acid oxidation and lipid metabolism. The wealth of data relating to this peptide suggests that it may be an excellent target in therapeutic management of diabetes and cardiovascular disease associated with obesity. While a novel agent targeting FGF21, the analogue PF-05231023, reduced plasma triglycerides this was also associated with increased blood pressure and heart rate.
This study enrolled 107 obese, hypertriglyceridaemic subjects treated with atorvastatin, with or without type 2 diabetes. These individuals were randomly allocated to PF-05231023 or placebo intravenously once-weekly for 4 weeks. At day 25, PF-05231023 treatment was associated with reduction in plasma triglycerides (by 33-43%) and an increase in high-density lipoprotein cholesterol concentration (by 15-28%), without significant changes in body weight. However, treatment was also associated with dose-related increases in blood pressure and heart rate. These results call into question the potential of this therapeutic approach for managing elevated triglycerides associated with obesity.