2型糖尿病患者中与噻唑烷二酮类药物和他汀类药物相关的肌病风险：一项巢式病例对照分析。

Koro Carol E, Sowell Margaret O, Stender Monika, Qizilbash Nawab

Worldwide Epidemiology, GlaxoSmithKline, Collegeville, Pennsylvania 19426, USA.

Clin Ther. 2008 Mar;30(3):535-42. doi: 10.1016/j.clinthera.2008.02.008.

BACKGROUND

The implementation of more aggressive goals for low-density lipoprotein cholesterol lowering in subjects with type 2 diabetes (T2D) and the expected increase in the use of statins is likely to increase the concomitant use of thiazolidinediones (TZDs) and statins.

OBJECTIVE

This study evaluated whether concomitant use of TZDs and statins is associated with an increased risk of myopathic events in subjects with T2D.

METHODS

This was a nested case-control study in subjects with T2D. Cases and controls were identified from a cohort of 125,394 subjects with T2D in the Integrated Healthcare Information Services database. Each case with a myopathic event (rhabdomyolysis, myositis, myopathy, or myalgia) was matched to up to 6 controls by age (+/-5 years), sex, calendar year of diagnosis of a myopathic event, and length of follow-up in the database. Incident cases of myopathy were identified using the following International Classification of Diseases, Ninth Revision codes: 359.x for myopathy, 728.88 for rhabdomyolysis, and 729.1 for unspecified myalgia and myositis. Prescription claims were used as a proxy for drug exposure. Five categories of exposure were employed: statins only, TZDs only, concomitant TZDs and statins, other antidiabetic agents only, and neither statins nor antidiabetic agents. Exposure to statins and/or TZDs within 90 days before the case index date was defined as recent exposure, and exposure at any time before the case index date was defined as ever exposure. Concomitant exposure to TZDs and statins, either recent or ever, was defined by an overlap of at least 30 days in the days supply of TZDs and statins during the exposure period.

RESULTS

The 3696 cases of myopathy were matched with 21,871 controls. The adjusted odds ratio (OR) for myopathic events for ever exposure to concomitant TZDs and statins compared with statins alone was 1.03 (95% CI, 0.83-1.26). Compared with neither statins nor antidiabetic agents, ever use of statins alone was associated with an increased likelihood of myopathic events (adjusted OR=1.36; 95% CI, 1.12-1.64). The likelihood of myopathic events was not significantly different for TZDs compared with other antidiabetic agents.

CONCLUSION

In this population of subjects with T2D, concomitant use of statins and TZDs was not associated with an increased risk of myopathic events beyond that conferred by statins alone.

背景

在2型糖尿病（T2D）患者中实施更积极的降低低密度脂蛋白胆固醇目标以及他汀类药物使用预期的增加，可能会使噻唑烷二酮类药物（TZDs）和他汀类药物的联合使用增多。

目的

本研究评估TZDs与他汀类药物的联合使用是否会增加T2D患者发生肌病事件的风险。

方法

这是一项针对T2D患者的巢式病例对照研究。病例和对照来自综合医疗保健信息服务数据库中125394例T2D患者队列。每例发生肌病事件（横纹肌溶解、肌炎、肌病或肌痛）的患者，按照年龄（±5岁）、性别、肌病事件诊断的日历年以及在数据库中的随访时长，与最多6名对照进行匹配。使用以下国际疾病分类第九版编码来识别新发肌病病例：肌病为359.x，横纹肌溶解为728.88，未特定的肌痛和肌炎为729.1。处方记录用作药物暴露的替代指标。采用了五类暴露情况：仅使用他汀类药物、仅使用TZDs、联合使用TZDs和他汀类药物、仅使用其他抗糖尿病药物以及既不使用他汀类药物也不使用抗糖尿病药物。病例索引日期前90天内暴露于他汀类药物和/或TZDs被定义为近期暴露，病例索引日期前任何时间的暴露被定义为既往暴露。联合暴露于TZDs和他汀类药物，无论是近期还是既往暴露，定义为暴露期间TZDs和他汀类药物的供应天数至少有30天重叠。

结果

3696例肌病病例与21871名对照进行了匹配。与仅使用他汀类药物相比，既往联合暴露于TZDs和他汀类药物发生肌病事件的校正比值比（OR）为1.03（95%CI，0.83 - 1.26）。与既不使用他汀类药物也不使用抗糖尿病药物相比，仅使用他汀类药物与发生肌病事件的可能性增加相关（校正OR = 1.36；95%CI，1.12 - 1.64）。与其他抗糖尿病药物相比，TZDs发生肌病事件的可能性无显著差异。