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

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/m(2). 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% [3.71 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 (< 100 mg/dL) were not significantly different between the 2 groups. The proportion of patients who achieved the combined end point of non HDL-C < 130 mg/dL and LDL-C < 100 mg/dL was significantly greater with fenofibrate/pravastatin compared with simvastatin monotherapy (41 [28.5%] vs 26 [17.9%]; P < 0.05). The prevalences of patients who experienced adverse event were not statistically different between the fenofibrate/pravastatin and simvastatin groups (17.2% vs 15.1%). However, compared with simvastatin monotherapy, the combination treatment was associated with significantly greater increases in alanine aminotransferase (+9.6% vs +1.5%; P = 0.03 between groups), creatinine (+13.7% vs +6.8%; P = 0.002 between groups), and homocysteine ( +36.5% vs +1.6%; P < 0.001 between groups) concentrations. Conclusions: In this selected population of adults with type 2 diabetes, the fenofibrate/pravastatin 160/40 mg FDC was associated with significantly greater changes from baseline in non-HDL-C, triglyceride, and HDL-C concentrations compared with simvastatin 20 mg. Both treatments were well tolerated. (Clin Ther. 2011;33:1-12) (c) 2011 Elsevier HS Journals, Inc.