Efficacy and Safety of Fenofibric Acid Co-Administered with Low- or Moderate-Dose Statin in Patients with Mixed Dyslipidemia and Type 2 Diabetes Mellitus Results of a Pooled Subgroup Analysis from Three Randomized, Controlled, Double-Blind Trials

Background: Monotherapy with lipid-modifying medication is frequently insufficient to normalize lipid abnormalities in patients with mixed dyslipidemia and type 2 diabetes mellitus. Objective: To evaluate the efficacy and safety of fenofibric acid + statin combination therapy in this population. Study Design: A pooled, subgroup analysis of three randomized, controlled, double-blind, 12-week trials. Setting: Multiple clinical research facilities in the US and Canada. Patients: Patients with mixed dyslipidemia and type 2 diabetes (n = 586). Intervention: Fenofibric acid (Trilipix (R)) 135 mg monotherapy; low-, moderate-, or high-dose statin monotherapy (rosuvastatin [Crestor (R)] 10, 20, or 40 mg; simvastatin [Zocor (R)] 20, 40, or 80 mg; or atorvastatin [Lipitor (R)] 20, 40, or 80 mg); or fenofibric acid + low-or moderate-dose statin. Main Outcome Measure: Mean percentage changes in lipid parameters, percentages of patients achieving optimal serum lipid/apolipoprotein levels, and incidence of adverse events. Results: Fenofibric acid + low-dose statin resulted in significantly (p < 0.001) greater mean percentage changes in high-density lipoprotein cholesterol (HDL-C) [16.8%] and triglycerides (-43.9%) than low-dose statin monotherapy (4.7% and -18.1%, respectively) and significantly (p < 0.001) greater reductions in low-density lipoprotein cholesterol (LDL-C) [-34.0%] than fenofibric acid monotherapy (-5.3%). Similarly, fenofibric acid + moderate-dose statin resulted in significantly (p <= 0.011) greater mean percentage changes in HDL-C (16.3%) and triglycerides (-43.4%) than moderate-dose statin monotherapy (8.7% and 24.2%, respectively) and significantly (p < 0.001) greater reductions in LDL-C (-32.6%) than fenofibric acid monotherapy (-5.3%). Compared with low-or moderate-dose statin, fenofibric acid + low-or moderate-dose statin resulted in over 5-fold higher percentages of patients achieving optimal levels of LDL-C, non-HDL-C, apolipoprotein B, HDL-C, and triglycerides simultaneously. Incidence of adverse events was generally similar among treatments. Conclusion: Fenofibric acid+ statin combination therapy in patients with mixed dyslipidemia and type 2 diabetes was well tolerated and resulted in more comprehensive improvement in the lipid/apolipoprotein profile than either monotherapy.