Statin Use and Risk of Diabetes Mellitus in Postmenopausal Women in the Women's Health Initiative

Abstract

Given the success of statins in both primary and secondary prevention of cardiovascular morbidity and mortality,^1-6 their use is progressively increasing, especially among older Americans.⁷ With such widespread use, even small risks are apparent alongside benefits. One emerging risk is an increased incidence of diabetes mellitus (DM). There is evidence that incident DM associated with statin use may be more common in the elderly, in women, and in Asians.^8-12 A recent analysis suggests that preexisting metabolic risk factors control incident DM rate with statin medication.¹³ It is unclear if this risk varies with individual statins or if this is a dose-driven class effect.^9,14 Although experimental and clinical studies find that individual statins act differently on glucose homeostasis as a function of relative lipophilicity and/or potency of action,¹⁵ other findings differ. A recent meta-analysis of 17 randomized controlled trials by Mills et al¹⁶ found a class effect increase of new-onset DM with statins (odds ratio [OR], 1.09; 95% CI, 1.02-1.16) similar to that reported by Sattar et al.⁹ Possibly, the grouping of statins masks the effect variation of individual statins. Still, at some given dose threshold, differences may be overcome, as implied by a meta-analysis of 5 trials comparing intensive to moderate dosing regimens using mainly atorvastatin and simvastatin.^13,17 Notably, meta-analysis results display intertrial and intratrial variability in diagnostic and statistical methods and do not consistently consider confounding factors. Moreover, contributing sample sizes do not permit balanced comparison by statin type, sex, race/ethnicity, and age. Similarly, single studies may uncover only part of a greater topography.