Efficacy of combination of Ezetimibe 10 mg and rosuvastatin 2.5 mg versus rosuvastatin 5 mg monotherapy for hypercholesterolemia in patients with type 2 diabetes

Abstract

Background: Statins are used to treat hypercholesterolemia in patients with type 2 diabetes mellitus, but many of these patients fail to achieve the target LDL-C level. Recent reports have suggested that a synergistic effect can be obtained by concomitant administration of the cholesterol absorption inhibitor ezetimibe and a statin. However, in patients with type 2 diabetes who are already being treated with satins, it remains unclear whether it is more effective to add ezetimibe or to increase the statin dose. Therefore, this study was performed to examine the effects of these two regimens on LDL-C and lipoproteins.

Methods: The subjects were type 2 diabetic patients under treatment with rosuvastatin (2.5 mg daily), who had LDL-C levels ≥80 mg/dL. They were randomly allocated to a group that received add-on therapy with ezetimibe at 10 mg/day (combination group, n = 40) or an increase of the rosuvastatin dose to 5 mg/day (dose escalation group, n = 39). These two groups were compared at baseline and after 12 weeks of treatment.

Results: The percent change of LDL-C was -31% in the combination group and -12% in the dose escalation group. Both groups showed a significant decrease, but the decrease was greater in the combination group. In both groups, there was a significant decrease in the levels of small dense LDL-C, oxidized LDL and remnant-like lipoprotein cholesterol. For all of these parameters, the percent changes were greater in the combination group. Only the combination group showed a significant decrease of triglycerides. Multivariate analysis was performed to identify factors associated with reaching an LDL-C level <80 mg/dL. As a result, add-on therapy with ezetimibe was extracted as a factor related to improvement of LDL-C.

Conclusions: Compared with increasing the dose of rosuvastatin, the combination of rosuvastatin and ezetimibe not only achieves quantitative but also qualitative improvement of serum lipid levels in type 2 diabetic patients, suggesting that this combination could suppress the progression of atherosclerosis.

Trial registration: UMIN000011005.

Figure 1

Percent changes from baseline of Serum lipids. Mean percent change from baseline (mean [SD]) of low-density lipoprotein cholesterol (LDL-C) (A), small dense low-density lipoprotein cholesterol (sdLDL-C) (B), malondialdehyde-modified low-density lipoprotein (MDA-LDL) (C), high-density lipoprotein cholesterol (HDL-C) (D), triglycerides (TG) (E), and remnant-like particle cholesterol (RLP-C) (F) after 12 weeks of treatment. R/E 2.5/10 mg indicates rosuvastatin 2.5 mg + add-on ezetimibe 10 mg; R 5 mg indicates rosuvastatin 5 mg. Open columns indicate R/E 2.5/10 mg; filled columns indicate R 5 mg. Values are the means ± SD. Data were compared by Student’s t-test for normally distributed variables and the Mann–Whitney U test for variables with a skewed distribution.