Commentary on ‘Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: A meta-analysis’ by Preiss et al.

High-dose statin therapy has been shown to reduce cardiovascular morbidity and mortality in high-risk patients. In general, statins are considered as having few side effects, but data from recent clinical trials suggest that these drugs may increase the incidence of diabetes. Moreover, a recent meta-analysis of 13 randomized statin trials of over 91,000 patients with mean follow-up of 4.1 years suggested that statin therapy compared with placebo leads to a 9% increased relative risk for the development of diabetes. ¹ Still hitherto it is unknown whether high-dose statin therapy compared with moderate-dose statin therapy also increases the risk of diabetes. Preiss et al. performed a meta-analysis of 5 statin trials with 32,752 participants without diabetes at baseline comparing intensive-dose statin therapy with moderate-dose statin therapy. ² The following trials were included: PROVE IT-TIMI 22, A to Z, TNT, IDEAL and SEARCH. Per 1000 patient-years two additional cases of diabetes were observed in the intensive-dose group, leading to an odds ratio of 1.12 for new-onset diabetes. In contrast, intensive statin therapy led to a 16% risk reduction for cardiovascular events. Thus, the number needed to harm for intensive statin therapy compared with moderate-dose statin therapy was 498 for new-onset diabetes per year while the number needed to treat to prevent 1 cardiovascular event was 155 per year. The benefits of high-dose statin therapy with respect to cardiovascular event reduction were consistent across all subgroups and consistent for each component of the primary endpoint including cardiovascular mortality. In contrast, for new-onset diabetes the study suggests that the risk for the development of diabetes with intensive statin therapy was higher among individuals with triglyceride concentrations below the median level of distribution. For any other subgroup there was no difference for the risk of incident diabetes.

Commentary

This study adds to our current understanding on the effects of statin therapy on the risk of developing diabetes. Previous data suggested that statin therapy in general may increase the risk of diabetes compared with placebo, but the present meta-analysis suggests that this increase is dose-dependent.These data, as well as the recently published analysis by Sattar et al., ¹ demonstrates that there is no difference between hydrophilic and lipophilic statins with respect to diabetes risk. Future studies are warranted to elucidate the underlying mechanisms behind the increase in diabetes risk with statin therapy. However, both analyses clearly demonstrate that the benefit of cardiovascular risk reduction by statin therapy far exceeds the risk of diabetes development. Therefore, statin therapy should remain a cornerstone of cardiovascular risk reduction in both patients with high cardiovascular risk in primary prevention as well as patients with established cardiovascular disease.