Effect of Ezetimibe Add-On Therapy on Non-HDL-C in Type 2 Diabetes Subjects—A Post-Hoc Analysis of RESEARCH Study

Background: In RESEARCH study, we demonstrated the superiority of ezetimibe add-on therapy over statin-doubling in T2DM.Non-HDL-C is attracting attention as an index including TG rich lipoproteins reflecting insulin resistance in diabetics. Methods: 109 T2DM adults with LDL-C >=120 mg/dL (>=100 mg/dL in secondary preventive) despite statin treatment were randomly assigned to statin doubling group (S) or adding ezetimibe (E) for 12 weeks.As a post-hoc analysis, non-HDL-C change and TG rich lipoproteins were analyzed. Results: The rate of non-HDL-C reduction was significantly greater in E(20.9%) than in S(8.3%). Assuming the non-HDL-C target as <150 mg/dl (<130 mg/dl for secondary preventive), the achievement rate was significantly higher in E(88.7%) than in S(57.1%). The rates of apoB and apoE reduction were significantly larger in E (apoB 14.8% and apoE 7.7%) than in S (apoB 9.0% and apoE 2.9%). By regression analysis, apoE change rate showed correlation with sd-LDL change rate or RLP-C change rate, respectively, with larger correlation and regression coefficient in E. The percentage change in non-HDL-C was correlated with the percentage change in sd-LDL, with larger regression coefficient in E. Analysis was also made for 43 subjects with TG>=150 mg/dl before treatment, and 73 subjects without achievement in the non-HDL-C target before treatment. Non-HDL-C reduction rates were greater in E (21.1% and 25.1%) than in S (8.9% and 8.7%), respectively. Target achievement rates were also significantly larger in E (77.8% and 83.9%) than in S (48.0% and 42.9%). ApoB reduction was 13.2% and 11.6% in S, and 12.5% and 17.1% E, and apoE reduction was 9.4% and 5.4% in S and 13.0% and 9.4% in E, respectively. The correlation of change rates showed almost the same tendency compared to the whole population. Conclusion: Ezetimibe combination therapy effectively reduced non-HDL-C reflecting TG rich lipoproteins, compared with statin-doubling therapy. Disclosure K. Sakamoto: None. M. Kawamura: None. M. Tagami: None. A. Tanaka: Research Support; Self; Daiichi Sankyo Company, Limited. Speaker's Bureau; Self; Merck Sharp & Dohme Corp., Kewpie Corporation. Y. Mori: None. T. Hirano: Speaker's Bureau; Self; Novo Nordisk Inc., AstraZeneca. T. Shiba: Speaker's Bureau; Self; Shionogi & Co., Ltd., Pfizer Inc., Merck Sharp & Dohme Corp., Kowa Company, Ltd., Daiichi Sankyo Company, Limited.