钠-葡萄糖共转运蛋白2抑制剂引起不良事件数据的挖掘与分析

Excavation and analysis of adverse events induced by sodium-glucose cotransporter 2 inhibitors

目的:挖掘分析我国上市的四种钠-葡萄糖共转运蛋白2抑制剂(SGLT2i)达格列净、恩格列净、卡格列净和艾托格列净在真实世界临床应用中药品不良事件(ADE)发生情况,为临床合理用药提供参考。方法:采用回顾性研究方法,收集美国食品药品监督管理局不良事件报告系统、世界卫生组织个例安全性病例报告数据库及欧盟药品不良反应数据库接收的4种药品ADE进行信号挖掘,检测药品安全信号。结果:SGLT2i的ADE主要集中在18~64岁人群。发生感染、代谢营养类疾病比例最高。4种药品中达格列净相关内分泌系统疾病及药品问题ADE较多;恩格列净高危安全信号主要集中在先天性、家族性、遗传性疾病,生殖系统及乳腺疾病;卡格列净应注意在内外科操作治疗、妊娠期、产褥期、围产期的应用;艾托格列净报告数量少且较分散。结论:临床应用SGLT2i需结合患者年龄及合并疾病进行个体化治疗,警惕并及时处理ADE。

Objective:To excavate and analyze the adverse drug events(ADE)induced by four kinds of sodium-glucose cotransporter 2 inhibitors(SGLT2i)including dapagliflozin,empagliflozin,canagliflozin and ertugliflozin,in order to provide references for rational drug use in clinic.Methods:The ADE reports associated with 4 kinds of SGLT2i were extracted from the FDA Adverse Event Reporting System(FAERS),the WHO Global Case Safety Report Database(VigiBase)and the European Drug Administration's Drug Alert Database(EudraVigilance)for signal mining to detect drug safety signals.Results:The ADEs of SGLT2i were mainly concentrated in people aged 18-64 years old.The proportion of infection,metabolic and nutritional diseases were the highest.Among 4 kinds of SGLT2i,there were more endocrine system diseases and drug problems ADE related to dapagliflozin;The high-risk safety signals of empagliflozin were mainly concentrated in congenital familial genetic diseases,reproductive system and breast diseases;Attention should be paid to the application of canagliflozin in the operation treatment of internal and external,pregnancy,puerperium and perinatal period;The number of ertugliflozin reports was small and scattered.Conclusion:Clinical application of SGLT2i required individualized treatment combined with patient's age and combined disease,and ADE should be dealed with timely.