An open, randomized, four-phased crossover study using 400 mg of bezafibrate or 200 mg of fenofibrate was performed. Study subjects were 14 dyslipidemia with impaired glucose tolerance or type 2 diabetes mellitus (61 ± 16 years, body mass index (BMI) 26 ± 3 kg/m2, total cholesterol (TC) 219 ± 53 mg/dL, triglyceride (TG) 183 ± 83 mg/dL, high-density lipoprotein-cholesterol (HDL-C) 46 ± 8 mg/dL, fasting plasma glucose 133 ± 31 mg/dL and HbA1c 6.2 ± 0.8 % ). Subjects were given either bezafibrate or fenofibrate for 8 weeks, discontinued for 4 weeks and then switched to the other fibrate for 8 weeks. Circulating PCSK9 levels and other metabolic parameters, including adiponectin, leptin and urine 8-hydroxy-2′-deoxyguanosine (8-OHdG) were measured at 0, 8, 12 and 20 weeks.
Plasma PCSK9 concentrations were significantly increased (+39.7 % for bezafibrate and +66.8 % for fenofibrate, p < 0.001) in all patients except for one subject when treated with bezafibrate. Both bezafibrate and fenofibrate caused reductions in TG (x2212;38.3 % , p < 0.001 vs. x2212;32.9 % , p < 0.01) and increases in HDL-C (+18.0 % , p < 0.001 vs. +11.7 % , p < 0.001). Fenofibrate significantly reduced serum cholesterol levels (TC, x2212;11.2 % , p < 0.01; non-HDL-C, x2212;17.3 % , p < 0.01; apolipoprotein B, x2212;15.1 % , p < 0.01), whereas bezafibrate significantly improved glucose tolerance (insulin, x2212;17.0 % , p < 0.05) and metabolic markers (γ-GTP, x2212;38.9 % , p < 0.01; adiponectin, +15.4 % , p < 0.05; urine 8-OHdG/Cre, x2212;9.5 % , p < 0.05).
Both bezafibrate and fenofibrate increased plasma PCSK9 concentrations. The addition of a PCSK9 inhibitor to each fibrate therapy may achieve beneficial cholesterol lowering along with desirable effects of respective fibrates.