Long-term fenofibrate therapy increases fibroblast growth factor 21 and retinol-binding protein 4 in subjects with type 2 diabetes.

Abstract

Fenofibrate is a peroxisome proliferator-activated receptor (PPAR)-α agonist that showed beneficial effects on total cardiovascular risk in patients with type 2 diabetes in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. This study aimed to investigate the long-term effect of fenofibrate therapy on three novel biomarkers of cardiovascular risk, namely adipocyte-fatty acid-binding protein (A-FABP), fibroblast growth factor 21 (FGF21), and retinol-binding protein 4 (RBP4), which are all downstream targets of PPAR-α or PPAR-γ, in patients with type 2 diabetes. A total of 216 patients (108 in the fenofibrate group and 108 in the placebo group) were randomly selected from the FIELD study cohort. A-FABP, FGF21, and RBP4 levels were measured in serum samples at both baseline and the fifth year of the study. Relative to the placebo group, the changes of serum FGF21 and RBP4 levels were 85% (P < 0.001) and 10% (P = 0.032) higher in the fenofibrate group, respectively, over 5 yr. Fenofibrate treatment had no detectable effect on serum A-FABP level (P > 0.05). The effect of fenofibrate treatment on serum FGF21, but not RBP4, remained significant after adjusting for fenofibrate-induced changes in glycosylated hemoglobin, total cholesterol, triglycerides, apolipoprotein A-II, fibrinogen, plasma creatinine, and homocysteine (P = 0.002). Long-term fenofibrate treatment could increase serum FGF21 levels over 5 yr in patients with type 2 diabetes. Additional studies are needed to investigate the potential role of FGF21 in the fenofibrate-mediated reduction of cardiovascular risk.