Mechanisms
Only atorvastatin, not fenofibrate, lowers CETP activity in metabolic syndrome patients despite both lowering triglycerides (Diabetes 2003)
Original title: Differential regulation of lipoprotein kinetics by atorvastatin and fenofibrate in subjects with the metabolic syndrome
In a crossover trial, 11 dyslipidemic men with metabolic syndrome received atorvastatin (40 mg/day) or micronised fenofibrate (200 mg/day) to compare effects on apoAI and apoB kinetics using stable-isotope tracer methodology. Atorvastatin significantly lowered cholesterol, triglycerides, LDL cholesterol, and VLDL/IDL/LDL apoB (all P<0.001) by increasing their fractional catabolic rates, while fenofibrate significantly lowered triglycerides and VLDL apoB, raised HDL2, HDL3, apoAI, and apoAII, and increased both the production and catabolic rate of apoAI, without significantly changing LDL cholesterol. Both drugs lowered triglycerides and apoCIII, but only atorvastatin significantly lowered plasma CETP activity (P<0.001), and neither drug affected insulin resistance. The authors conclude these differential kinetic effects support combining atorvastatin and fenofibrate to optimally manage dyslipoproteinemia in metabolic syndrome.
Original abstract
The metabolic syndrome is characterized by insulin resistance and abnormal apolipoprotein AI (apoAI) and apolipoprotein B-100 (apoB) metabolism that may collectively accelerate atherosclerosis. The effects of atorvastatin (40 mg/day) and micronised fenofibrate (200 mg/day) on the kinetics of apoAI and apoB were investigated in a controlled cross-over trial of 11 dyslipidemic men with the metabolic syndrome. ApoAI and apoB kinetics were studied following intravenous d(3)-leucine administration using gas-chromatography mass spectrometry with data analyzed by compartmental modeling. Compared with placebo, atorvastatin significantly decreased (P < 0.001) plasma concentrations of cholesterol, triglyceride, LDL cholesterol, VLDL apoB, intermediate-density lipoprotein (IDL) apoB, and LDL apoB. Fenofibrate significantly decreased (P < 0.001) plasma triglyceride and VLDL apoB and elevated HDL(2) cholesterol (P < 0.001), HDL(3) cholesterol (P < 0.01), apoAI (P = 0.01), and apoAII (P < 0.001) concentrations, but it did not significantly alter LDL cholesterol. Atorvastatin significantly increased (P < 0.002) the fractional catabolic rate (FCR) of VLDL apoB, IDL apoB, and LDL apoB but did not affect the production of apoB in any lipoprotein fraction or in the turnover of apoAI. Fenofibrate significantly increased (P < 0.01) the FCR of VLDL, IDL, and LDL apoB but did not affect the production of VLDL apoB. Relative to placebo and atorvastatin, fenofibrate significantly increased the production (P < 0.001) and FCR (P = 0.016) of apoAI. Both agents significantly lowered plasma triglycerides and apoCIII concentrations, but only atorvastatin significantly lowered (P < 0.001) plasma cholesteryl ester transfer protein activity. Neither treatment altered insulin resistance. In conclusion, these differential effects of atorvastatin and fenofibrate on apoAI and apoB kinetics support the use of combination therapy for optimally regulating dyslipoproteinemia in the metabolic syndrome.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.