Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, Korea.
Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Korea.
Endocrinol Metab (Seoul). 2022 Feb;37(1):65-73. doi: 10.3803/EnM.2021.1275. Epub 2022 Feb 8.
Most studies of systematic drug repositioning have used drug-oriented data such as chemical structures, gene expression patterns, and adverse effect profiles. As it is often difficult to prove repositioning candidates' effectiveness in real-world clinical settings, we used patient-centered real-world data for screening repositioning candidate drugs for multiple diseases simultaneously, especially for diabetic complications.
Using the National Health Insurance Service-National Sample Cohort (2002 to 2013), we analyzed claims data of 43,048 patients with type 2 diabetes mellitus (age ≥40 years). To find repositioning candidate disease-drug pairs, a nested case-control study was used for 29 pairs of diabetic complications and the drugs that met our criteria. To validate this study design, we conducted an external validation for a selected candidate pair using electronic health records.
We found 24 repositioning candidate disease-drug pairs. In the external validation study for the candidate pair cerebral infarction and glycopyrrolate, we found that glycopyrrolate was associated with decreased risk of cerebral infarction (hazard ratio, 0.10; 95% confidence interval, 0.02 to 0.44).
To reduce risks of diabetic complications, it would be possible to consider these candidate drugs instead of other drugs, given the same indications. Moreover, this methodology could be applied to diseases other than diabetes to discover their repositioning candidates, thereby offering a new approach to drug repositioning.
大多数系统药物再定位研究都使用了以药物为导向的数据，如化学结构、基因表达模式和不良反应谱。由于在真实临床环境中很难证明再定位候选药物的有效性，因此我们使用以患者为中心的真实世界数据来同时筛选多种疾病的再定位候选药物，特别是糖尿病并发症。
我们使用国民健康保险服务-国家样本队列（2002 年至 2013 年）分析了 43048 例 2 型糖尿病（年龄≥40 岁）患者的理赔数据。为了找到再定位候选疾病-药物对，我们对 29 对糖尿病并发症和符合我们标准的药物进行了嵌套病例对照研究。为了验证该研究设计，我们使用电子健康记录对选定的候选药物对进行了外部验证。
我们发现了 24 个再定位候选疾病-药物对。在对候选药物对脑梗死和吡咯烷酮的外部验证研究中，我们发现吡咯烷酮与脑梗死风险降低相关（风险比，0.10；95%置信区间，0.02 至 0.44）。
为了降低糖尿病并发症的风险，可以考虑在相同适应证下使用这些候选药物替代其他药物。此外，该方法可以应用于除糖尿病以外的疾病，以发现其再定位候选药物，从而为药物再定位提供一种新方法。
