OBJECTIVES: Evidence from clinical trials indicates that high-intensity statins reduce atherosclerotic cardiovascular risk more than moderate- or low-intensity statins, especially in secondary prevention of cardiovascular disease. However, the cardiovascular benefits offered by high-intensity statins may be offset by the greater possibility of side effects, including the potential for increased diabetes risk as noted in recent studies. The objective of the study was to compare the risk of diabetes among patients using intensive- and moderate-dose statins. In addition, we examined the co-association of treatment duration and statin dosage intensity on the risk of diabetes.

METHODS: We performed a retrospective database analysis of the 2003-2004 Thomson Reuters MarketScan® Commercial Claims Database and identified 58,112 new statin users aged 20 – 63 years who did not have a history of diabetes. We used Cox proportional hazards regression to estimate the hazards of diabetes for intensive- and moderate-dose statin users, adjusting for baseline demographic and clinical variables, including age, gender, Charlson comorbidity index score, hypertension, obesity, and medication adherence. In addition, we examined the potential modifying effects of treatment duration on statin dosage intensity and the associated risk of diabetes.

RESULTS: Study results indicated that intensive-dose statin users had a 42% increased risk of diabetes compared to moderate-dose statin users (HR=1.42; 99% CI=1.24, 1.63; p<0.001). In addition, risk of diabetes was associated with the use of intensive doses of simvastatin (HR=1.71; p<0.001) and atorvastatin (HR=1.38, p<0.001), but not of rosuvastatin (HR=1.09; p=0.72). Statin users on long-term (≥ 3 months) therapy had a higher risk of diabetes (HR=1.30; p=0.001).

CONCLUSIONS: Since sustained statin therapy is needed to achieve optimal cardiovascular outcomes, long-term therapy with moderate-dose statins appears to confer a lower diabetes risk and may be optimal, especially among patients with lower cardiovascular risk profiles.