Ezetimibe alone and in combination lowers the concentration of small, dense low-density lipoproteins in type 2 diabetes mellitus.

OBJECTIVE: The effectiveness of the cholesterol absorption inhibitor ezetimibe on LDL subfractions and ultimately on the atherosclerotic risk profile remains controversial. We thus determined the concentration of atherogenic small, dense LDL (sdLDL) in patients with type 2 diabetes and an elevated cardiovascular risk profile. RESEARCH DESIGN AND METHODS: Multicenter, randomized, open-label 6-week study investigating the effect of ezetimibe 10mg (E), simvastatin 20mg (S) and the combination of ezetimibe-/simvastatin 10/20mg (C) on the concentration of sdLDL separated from fresh plasma by gradient ultracentrifugation in patients with type 2 diabetes (NCT01384058). RESULTS: Fifty-six patients were screened for sdLDL, 41 were randomized, and 40 patients (12 E, 14 S and 14 C) completed the study. Total and LDL cholesterol fell by 14% (p=0.004) and 15% (p=0.006) with E, 22% (p<0.001) and 32% (p<0.001) with S, and 32% (p<0.001) and 44% (p<0.001) with C, respectively. E reduced the concentration of sdLDL by 20% (p=0.043) whereas S and C reduced sdLDL by 24% (p=0.020) and 33% (p=0.003), respectively, and non-sdLDL by 28% (p=0.004) and 42% (p<0.001), respectively. However, the further drop in sdLDL by adding E to S was not significant. CONCLUSION: Ezetimibe alone and in combination with simvastatin reduced the concentration of atherogenic sdLDL in patients with type 2 diabetes.