Comparison of the Effects of Simvastatin vs. Rosuvastatin vs. Simvastatin/Ezetimibe on Parameters of Insulin Resistance

E. Moutzouri; E. Liberopoulos; D. P. Mikhailidis; M. S. Kostapanos; A. A. Kei; H. Milionis; M. Elisaf


Int J Clin Pract. 2011;65(11):1141-1148. 

In This Article

Abstract and Introduction


Background: Statin treatment may be associated with adverse effects on glucose metabolism. Whether this is a class effect is not known. In contrast, ezetimibe monotherapy may beneficially affect insulin sensitivity.
Objective: The aim of this study was to compare the effects of three different regimens of equivalent lowdensity lipoprotein cholesterol (LDL-C) lowering capacity on glucose metabolism.
Methods: A total of 153 patients (56 men), who had not achieved the LDL-C goal recommended by the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) despite a 3-month dietary and lifestyle intervention, were randomly allocated to receive open-label simvastatin 40 mg or rosuvastatin 10 mg or simvastatin/ezetimibe 10/10 mg for 12 weeks. The primary end point was changes in homeostasis model assessment of insulin resistance (HOMA-IR). Secondary endpoints consisted of changes in fasting insulin levels, fasting plasma glucose (FPG), glycosylated haemoglobin (HbA1c), the HOMA of b-cell function (HOMA-B) (a marker of basal insulin secretion by pancreatic b-cells), LDL-C and high sensitivity C reactive protein (hsCRP).
Results: At week 12, all three treatment regimens were associated with significant increases in HOMA-IR and fasting insulin levels (p < 0.05 compared with baseline). No significant difference was observed between groups. No change in FPG, HbA1c and HOMA-B levels compared with baseline were noted in any of the three treatment groups. Changes in serum lipids and hsCRP were similar across groups.
Conclusion: To the extent that simvastatin 40 mg, rosuvastatin 10 mg and simvastatin/ezetimibe 10/10 mg are associated with adverse effects on insulin resistance, they appear to be of the same magnitude.


Statins are the cornerstone of both primary and secondary cardiovascular disease (CVD) prevention. However, concerns were recently raised regarding the effects of statins on carbohydrate metabolism.[1] In the Justification for the use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial an increase in the incidence of new-onset diabetes (NOD) associated with rosuvastatin treatment was observed.[2] Several meta-analyses have been conducted to elucidate the effect of statins on glucose metabolism.[3–5] Treatment with statins has been associated with a 9% increase in the risk of developing NOD without any differential effect among individual statins.[3,5] However, another meta-analysis showed that there may be differences among various statins.[4] In the latter meta-analysis, pravastatin appeared to improve insulin sensitivity, whereas simvastatin was associated with an adverse effect on glucose metabolism.[4] Also, atorvastatin and rosuvastatin non-significantly worsened insulin sensitivity.[4] We have previously shown that rosuvastatin administration in hypercholesterolemic patients with impaired fasting glucose (IFG) was associated with a dosedependent increase in insulin resistance.[6,7]

Ezetimibe is a cholesterol absorption inhibitor, which is mainly used in combination with statins. The combination of ezetimibe with low dose of statin results in similar low-density lipoprotein cholesterol (LDL-C) lowering compared with a high dose of the same statin.[8] Some studies have suggested that treatment with ezetimibe may be associated with beneficial effects on glucose metabolism.[9–11]

Simvastatin 40 mg, rosuvastatin 10 mg and the combination of simvastatin 10 mg with ezetimibe 10 mg result in LDL-C reductions of approximately the same magnitude.[12,13] However, the effects of these treatments on glucose metabolism have not been directly compared.

The present study compared the effects of simvastatin 40 mg, rosuvastatin 10 mg and simvastatin/ezetimibe 10/10 mg on indices of glucose metabolism in Greek hypercholesterolemic patients.


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