High-dose statins associated with more diabetes risk

Higher-dose statin therapy increased patients' risk of developing diabetes more than moderate-dose regimens, a new meta-analysis found.

The analysis included five randomized controlled trials comparing intensive-dose statin therapy (80 mg of simvastatin or atorvastatin) with moderate-dose therapy. The trials had 32,752 participants, all of whom were without diabetes at baseline. Over the course of the trials, 2,749 people developed diabetes: 1,449 from the intensive group and 1,300 from the moderate-dose group. That difference worked out to two additional cases per 1,000 patient-years in the intensive group and an increased odds ratio for developing diabetes of 1.12 (95% CI, 1.04 to 1.22). However, patients in the intensive group were less likely to experience cardiovascular events (3,134 vs. 3,550, 6.5 fewer events per 1,000 patient-years, odds ratio of 0.84 [95% CI, 0.75 to 0.94]).

Researchers calculated that, with intensive therapy, the number needed to harm for diabetes incidence was 498, while the needed to treat to prevent a cardiovascular event was 155. The results confirm recent evidence of an increased incidence of diabetes with statin therapy and indicate a dose-dependent association, the authors said. However, the mechanism is still unknown and it's unclear whether the risk applies to all patients or only specific groups. The authors concluded, “Given that cardiovascular risk from diabetes is modest in the first decade after diagnosis, and as the benefit of statin therapy increases over time and in absolute terms with increasing age, net cardiovascular benefit in high-risk individuals will still strongly favor statin therapy.”

They recommended that future research investigate the effect of intensive statins on patients with established diabetes, and that clinicians watch carefully for the development of diabetes in patients on intensive therapy. A registry could also be helpful in evaluating long-term effects of the regimen, the authors suggested. The study appeared the June 22/29 Journal of the American Medical Association.

The FDA recently recommended against starting patients on 80-mg doses of simvastatin due to the risk of myopathy.