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) 135 mg monotherapy; low-, moderate-, or high-dose statin monotherapy (rosuvastatin [Crestor] 10, 20, or 40 mg; simvastatin [Zocor] 20, 40, or 80 mg; or atorvastatin [Lipitor] 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 < or = 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. [Clinical trials are registered at www.clinicaltrials.gov: NCT00300482, NCT00300456, and NCT00300469].