Department of Pharmacy and Yonsei Institute of Pharmaceutical Sciences Research, College of Pharmacy, Yonsei University, 162-1 Songdo-dong, Yeonsu-gu, Incheon, South Korea.
Department of Pharmaceutical Medicine and Regulatory Sciences, College of Medicine and Pharmacy, Yonsei University, Incheon, South Korea.
Cardiovasc Diabetol. 2020 May 16;19(1):67. doi: 10.1186/s12933-020-01037-0.
We evaluated the effect of statin use on new-onset type 2 diabetes among individuals without atherosclerotic cardiovascular disease (ASCVD) using nationally representative South Korean claims data (2002-2013, N = 1,016,820).
A total of 13,698 patients (statin users 5273, non-statin users 5273) aged 40-74 years, newly diagnosed with dyslipidemia but without any history of diabetes or ASCVD, were selected in 2005. We followed up the final sample until 2013 and evaluated the cumulative incidence of type 2 diabetes. We used extended Cox regression models to estimate the time-varying adjusted hazard ratios of statin use on new-onset type 2 diabetes. We performed further analyses based on the cumulative defined daily dose of statin received per year to evaluate the degree of risk compared to non-statin users.
Over the mean follow-up period of 7.1 years, 3034 patients developed type 2 diabetes; the number of statin users exceeded that of non-users, demonstrating that statin use significantly increased the risk of new-onset type 2 diabetes. The risk of new-onset type 2 diabetes differed among statin users according to cDDD per year (adjusted HR = 1.31 [95% CI 1.18-1.46] for less than 30 cDDD per year; 1.58 [1.43-1.75] for 30-120 cDDD per year; 1.83 [1.62-2.08] for 120-180 cDDD per year; and 2.83 [2.51-3.19] for more than 180 cDDD per year). The diabetogenic effect of pitavastatin was not statistically significant, but the risk was the largest for atorvastatin. Long-term exposure (≥ 5 years) to statins was associated with a statistically significant increase in the risk of new onset type 2 diabetes in all statin subtypes explored, with the highest magnitude for simvastatin (HR = 1.916, 95% CI 1.647-2.228) followed by atorvastatin (HR = 1.830, 95% CI 1.487-2.252).
Statin use was significantly associated with an increased risk of new-onset type 2 diabetes. We also found a dose-response relationship in terms of statin use duration and dose maintenance. Periodic screening and monitoring for incident type 2 diabetes may be warranted in long-term statin users.
我们使用具有全国代表性的韩国理赔数据（2002-2013 年，N=1016820）评估了他汀类药物的使用对无动脉粥样硬化性心血管疾病（ASCVD）个体新发 2 型糖尿病的影响。
在 2005 年，共选择了 13698 名年龄在 40-74 岁、新诊断为血脂异常但无糖尿病或 ASCVD 病史的患者（他汀类药物使用者 5273 人，非他汀类药物使用者 5273 人）。我们随访了最终样本至 2013 年，并评估了 2 型糖尿病的累积发生率。我们使用扩展 Cox 回归模型来估计他汀类药物使用对新发 2 型糖尿病的时间变化调整后的危害比。我们根据每年接受的他汀类药物累积定义日剂量进行了进一步分析，以评估与非他汀类药物使用者相比的风险程度。
在平均 7.1 年的随访期间，有 3034 名患者发生 2 型糖尿病；他汀类药物使用者的数量超过了非使用者，表明他汀类药物的使用显著增加了新发 2 型糖尿病的风险。根据每年的 cDDD（定义日剂量），他汀类药物使用者新发 2 型糖尿病的风险存在差异（每年 cDDD 少于 30 时，调整后的 HR=1.31[95%CI 1.18-1.46]；30-120 时，1.58[1.43-1.75]；120-180 时，1.83[1.62-2.08]；超过 180 时，2.83[2.51-3.19]）。匹伐他汀的致糖尿病作用没有统计学意义，但阿托伐他汀的风险最大。所有探索的他汀类药物亚型中，长期（≥5 年）暴露于他汀类药物与新发 2 型糖尿病风险的显著增加相关，其中辛伐他汀的幅度最大（HR=1.916，95%CI 1.647-2.228），其次是阿托伐他汀（HR=1.830，95%CI 1.487-2.252）。
他汀类药物的使用与新发 2 型糖尿病的风险增加显著相关。我们还发现，他汀类药物使用持续时间和剂量维持方面存在剂量-反应关系。长期使用他汀类药物的患者可能需要定期筛查和监测新发 2 型糖尿病。
