Menopause Live (12 March, 2012) from IMS

Meta-analyses have shown an increased risk of incident type 2 diabetes associated with statin use. However, the risk increase has been estimated to be rather small (odds ratio 1.09; 95% confidence interval (CI) 1.02–1.17) [1] and, for instance, more pronounced in the elderly and associated with intensive-dose treatment [2]. 

In a recent study by Culver and colleagues [3], the association between baseline statin use and incident self-reported diabetes during 3 years of follow-up was assessed in 153 840 participants in the Women’s Health Initiative trial. The data comprise follow-up from 1 004 466 person-years. Of the study partici-pants, 143 006 (~93%) were not taking statins and, in these women, incident diabetes occurred in 9166 (~6.4%) women. A total of 10 834 women (~7%) were current statin users at baseline and diabetes was reported in 1076 (~10%) women at 3 years of follow-up.

The fully adjusted hazard ratio for statin use and incident diabetes was 1.48 (95% CI 1.38–1.59). Low-potency (fluvastatin, lovastatin and pravastatin) and high-potency statins (simvastatin and atorvastatin) showed similar risk associations (hazard ratio 1.45; 95% CI 1.36–1.61 and 1.48; 95% CI 1.36–1.61, respectively). Furthermore, statin use was associated with a significantly increased risk of diabetes, especially in women with a body mass index (BMI) below 25 kg/m2 compared with women with BMI of 30 kg/m2 or higher (hazard ratios and 95% CIs were 1.89; 1.57–2.29, and 1.20; 1.09–1.33, respectively).

Importantly, the study reveals that the increased risk of diabetes with statin use was similar within different age groups as well as among women with (hazard ratio 1.46; 95% CI 1.29–1.65) and without (1,48; 95% CI 1.36–1.62) history of cardiovascular disease.

Comment
Statin therapy is effective for reduction of cardiovascular events and is generally recognized as being safe and well tolerated [4]. However, one emerging risk is an increased incidence of diabetes mellitus. Although this risk has been estimated to be small [1], these findings are based on studies representing mainly men. Since sex differences in the pathogenesis of diabetes are well recognized, incident diabetes associated with statin use may be more common in women than men.

Results of this study by Culver and colleagues have important implications when balancing the risks and benefits of statins in women, particularly in the setting of primary prevention, since recent meta-analyses show no benefit on all-cause mortality [5]. Furthermore, since statin use was associated with increased risk of diabetes also in recently postmenopausal and lean women, it might be necessary to reconsider indications for statin use in these patient groups. Obviously, this observational study setting has various limitations and thus further studies are warranted before definite conclusions.

Tomi Mikkola
Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland

References
1. Sattar N, Preiss D, Murray HM, et al. Statins and risk of incident diabetes: a collaborate meta-analysis of randomised statin trials. Lancet 2010;375:735-42.
http://www.ncbi.nlm.nih.gov/pubmed/20167359
2. Preiss D, Seshasai SR, Welsh P, et al. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. JAMA 2011;305:2556-64.
http://www.ncbi.nlm.nih.gov/pubmed/21693744
3. Culver AL, Ockene IS, Balasubramanian R, et al. Statin use and the risk of diabetes mellitus in postmenopausal women in the Women’s Health Initiative. Arch Intern Med 2012;172:144-152.
http://www.ncbi.nlm.nih.gov/pubmed/22231607
4. Baigent C, Blackwell L, Emberson J, et al; Cholesterol Treatment Trialists’ (CTT) Collaboration. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 2010;376:1670-1681.
http://www.ncbi.nlm.nih.gov/pubmed/21067804
5. Ray KK, Seshasai SR, Erqou S, et al. Statins and all-cause mortality in high-risk primary prevention: a meta-analysis of 11 randomized controlled trials involving 65,229 participants. Arch Intern Med 2010;170:1024–31.
http://www.ncbi.nlm.nih.gov/pubmed/20585067