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Observational Study
. 2019 Apr 16;8(8):e011320.
doi: 10.1161/JAHA.118.011320.

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

Min Jung Ko  1 , Ae Jeong Jo  1 , Yun Jung Kim  1 , Shin Hee Kang  1 , Songhee Cho  1 , Sang-Ho Jo  2 , Cheol-Young Park  3 , Sung-Cheol Yun  4 , Woo Je Lee  5 , Duk-Woo Park  6
Affiliations
Observational Study

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

Min Jung Ko et al. J Am Heart Assoc. .

Abstract

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.

Keywords: diabetes mellitus; hypercholesterolemia; statin.

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Figures

Figure 1
Figure 1
Creation of the study population. Hypercholesterolemia was defined as total cholesterol levels of ≥240 mg/dL. ASCVD indicates atherosclerotic cardiovascular disease.
Figure 2
Figure 2
Cumulative risk of new‐onset diabetes mellitus in the matched cohort.
Figure 3
Figure 3
Association between statin therapy and the risk of new‐onset diabetes mellitus, according to duration, intensity, and cumulative dose of statins. Hazard ratios are for statin users as compared with statin nonusers in the propensity‐matched cohort. Adjusted PS Models were further adjusted for body mass index, baseline total cholesterol level, baseline fasting glucose level, and Charlson comorbidity index in the propensity‐matched cohort. HR indicates hazard ratio; PS, propensity‐score.
Figure 4
Figure 4
Hazard ratios for the risk of new‐onset diabetes mellitus in the propensity‐score–matched cohort, according to major clinical subgroups.
See this image and copyright information in PMC

Comment in

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