Time- and Dose-Dependent Association of Statin Use With Risk of Clinically Relevant New-Onset Diabetes Mellitus in Primary Prevention: A Nationwide Observational Cohort Study.

Background Given that statins are increasingly being used for primary-prevention, the public concerns regarding the risk of new-onset diabetes mellitus associated with statin use may be an issue. Methods and Results Using healthcare data from the national health insurance examinees, our study comprised a cohort of adults aged ≥40 years with hypercholesterolemia who would be eligible for statin therapy for primary prevention from 2005 to 2012. The primary outcome was the occurrence of clinically relevant new-onset diabetes mellitus requiring medical therapy. Among 2 162 119 adults with hypercholesterolemia who might be eligible for statin therapy, 638 625 (29.5%) ever used statins and 1 523 494 (70.5%) never used statins. In the propensity-matched cohort of 518 491 pairs, during mean follow-up of 3.9 years, being an ever-user of statin was significantly associated with diabetes mellitus risk compared with being a never-user of statin (13.4 versus 6.9 per 1000 person-years; adjusted hazard ratio [ HR ], 1.88; 95% CI , 1.85-1.93). With increasing duration of statin use, the risk of diabetes mellitus was proportionally increased ( HR 1.25 <1 year, HR 2.22 for 1-2 years, and HR 2.62 >2 years). An excess risk of diabetes mellitus was also associated with a higher intensity ( HR 1.75 for low-to-moderate potency and HR 2.31 for high potency) and a cumulative dosing of statin ( HR 1.06 for low-tertile, HR 1.74 for middle-tertile, and HR 2.52 for high-tertile of defined-daily-disease). Conclusions In patients receiving statin therapy for primary prevention, there was a time- and dose-dependent association of statin use with an increasing risk of new-onset diabetes mellitus.