Comparison of the effects of simvastatin vs. rosuvastatin vs. simvastatin/ezetimibe on parameters of insulin resistance

Abstract

Summary 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 low‐density 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 β‐cell function (HOMA‐B) (a marker of basal insulin secretion by pancreatic β‐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.

Increased risk of diabetes with statin treatment is associated with impaired insulin sensitivity and insulin secretion: a 6 year follow-up study of the METSIM cohort

“…Our study is also the first to show that statin therapy was associated with the worsening of 2 h hyperglycaemia at follow-up. Increased levels of FPG in non-diabetic individuals receiving statin therapy have been previously reported in some [26,27], but not all [20], studies; however, no previous study has reported significant changes in 2hPG level in people receiving statin treatment.…”

“…Studies of the effects of statin treatment on insulin sensitivity are conflicting and are generally small in size [14][15][16][17][18]. Treatment with simvastatin and rosuvastatin has decreased insulin sensitivity, whereas treatment with pravastatin has improved insulin sensitivity [19,20]. Statininduced decrease in insulin secretion has been reported in some [21], but not all, in vitro studies [22].…”

Effects of Rosuvastatin vs. Simvastatin/ezetimibe on Arterial Wall Stiffness in Patients with Coronary Artery Disease

“…Rosuvastatin was chosen because it has been proven to be the most effective hydrophilic statin in lowering cholesterol (10). Rosuvastatin (10 mg/day) and simvastatin/ezetimibe (10/10 mg) are considered to equally decrease the LDL-C level (11). A total of 36 CAD patients with 50% or more stenosis in at least one major coronary artery were divided into a rosuvastatin (n=18) and simvastatin/ezetimibe (n=18) group at random.…”

Use of statins and the incidence of type 2 diabetes mellitus

“…[30][31][32][33][34] Treatment with simvastatin and rosuvastatin has been shown to decrease insulin sensitivity, while treatment with pravastatin improved insulin sensitivity. 35,36 Reduction of insulin secretion caused by statin has been reported in some in vitro studies, 37 but other studies in this model showed no such decrease. 38 Data from large meta-analyzes assessing the risk of developing diabetes with statins, either compared to placebo 14 or compared to a less intensive treatment, 15 suggest a causal relationship.…”