Comparison of effects of bezafibrate and fenofibrate on circulating proprotein convertase subtilisin/kexin type 9 and adipocytokine levels in dyslipidemic subjects with impaired glucose tolerance or type 2 diabetes mellitus: results from a crossover study.

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Noguchi T, Kobayashi J, Yagi K, Nohara A, Yamaaki N, Sugihara M, Ito N, Oka R, Kawashiri MA, Tada H, Takata M, Inazu A, Yamagishi M, Mabuchi H

Atherosclerosis. 2011 Jul;217(1):165-70. doi: 10.1016/j.atherosclerosis.2011.02.012. Epub 2011 Feb 22.

PubMed ID

21411093 [ View in PubMed

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Abstract

BACKGROUND: Bezafibrate and fenofibrate show different binding properties against peroxisome proliferator-activated receptor subtypes, which could cause different clinical effects on circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) levels and on various metabolic markers. METHODS: An open, randomized, four-phased crossover study using 400 mg of bezafibrate or 200mg 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/m(2), 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. RESULTS: 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 (-38.3%, p<0.001 vs. -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, -11.2%, p<0.01; non-HDL-C, -17.3%, p<0.01; apolipoprotein B, -15.1%, p<0.01), whereas bezafibrate significantly improved glucose tolerance (insulin, -17.0%, p<0.05) and metabolic markers (gamma-GTP, -38.9%, p<0.01; adiponectin, +15.4%, p<0.05; urine 8-OHdG/Cre, -9.5%, p<0.05). CONCLUSION: 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.

DrugBank Data that Cites this Article

Pharmaco-proteomics

Drug	Drug Groups	Gene	Gene ID	Change	Interaction	Chromosome
Fenofibrate	Approved	APOB	338	decreased	Fenofibrate results in decreased expression of APOB protein	2p24.1
Bezafibrate	Approved Investigational	ADIPOQ	9370	increased	Bezafibrate results in increased expression of ADIPOQ protein	3q27.3
Bezafibrate	Approved Investigational	PCSK9	255738	increased	Bezafibrate results in increased expression of PCSK9 protein	1p32.3
Fenofibrate	Approved	PCSK9	255738	increased	Fenofibrate results in increased expression of PCSK9 protein	1p32.3