Fixed-Dose Combination Fenofibrate/Pravastatin 160/40 mg Versus Simvastatin 20 mg Monotherapy in Adults With Type 2 Diabetes and Mixed Hyperlipidemia Uncontrolled With Simvastatin 20 mg: A Double-Blind, Randomized Comparative Study

Abstract Background Patients with type 2 diabetes mellitus and mixed hyperlipidemia have an increased cardiovascular risk and may not achieve recommended LDL-C and non–HDL-C goals on statin monotherapy. This study was designed to obtain regulatory approval of a fenofibrate/pravastatin 160/40 mg fixed-dose combination (FDC) capsule. Objective The aim of this study was to compare the efficacy and tolerability of this FDC and simvastatin 20 mg in patients with type 2 diabetes. Methods This multicenter, randomized, double-blind, parallel-arm study was conducted in patients with type 2 diabetes and mixed hyperlipidemia, without cardiovascular disease, and who were not at lipid goals with simvastatin 20 mg monotherapy. After a 6-week run-in period during which patients received simvastatin 20 mg, those with non–HDL-C concentrations ≥130 mg/dL or LDL-C concentrations ≥100 mg/dL and triglyceride concentrations 150 to 600 mg/dL were enrolled. Eligible patients were randomly assigned to receive 12-week treatment with fenofibrate/pravastatin 160/40 mg FDC or simvastatin 20 mg once daily, followed by a 12-week open-label tolerability-assessment period during which all patients received the FDC. The primary efficacy outcome was the mean percentage change in non–HDL-C after 12 weeks. Secondary efficacy outcomes included changes in other lipid and lipoprotein parameters, fibrinogen, and high-sensitivity C-reactive protein. Tolerability was assessed based on the prevalence of adverse events and abnormal laboratory data in each treatment group. Results A total of 291 patients were randomized to receive fenofibrate/pravastatin (n= 145) or simvastatin (n = 146). The mean (SD) age of the participants was 56.6 (8.9) years, 48.1% were men, and the body mass index was 31.3 (4.6) kg/m2 . The FDC was associated with a significantly greater reduction in non–HDL-C (primary end point) compared with simvastatin monotherapy (–12.9% [1.8] vs –6.8% [1.8]; P = 0.008). Triglyceride (–28.6% [3.7] vs +5.0% [3.6]; P < 0.001), fibrinogen (–11.5% [1.6] vs +0.3% [1.6]; P < 0.001), and HDL-C (+6.3% [1.3] vs +1.8% [1.3]; P = 0.008) concentrations also were significantly improved with the FDC compared with simvastatin monotherapy. The proportions of patients who achieved the LDL-C target (