Page 100 - 《中国药房》2021年8期

·药物与临床·

SGLT2抑制剂不良反应信号的挖掘与评价 Δ

郑淑芬 1，2＊ ，钟诗龙 （1.南方医科大学药学院，广州 510515；2.广东省人民医院药学部，广州 510080）
1，2 #
中图分类号 R969.3 文献标志码 A 文章编号 1001-0408（2021）08-0986-05
DOI 10.6039/j.issn.1001-0408.2021.08.15
摘 要 目的：挖掘和评价钠-葡萄糖共转运蛋白2（SGLT2）抑制剂卡格列净、达格列净、恩格列净上市后的不良反应（ADR）信号，
为临床合理用药提供参考。方法：采用比例报告比法（PRR）和报告比值比法（ROR）对 2013 年第 2 季度至 2020 年第 3 季度美国
FDA不良事件报告系统自发呈报系统中接收的卡格列净、达格列净、恩格列净等3种SGLT2抑制剂的ADR进行信号挖掘，分析
ADR报告中对应患者的基本信息（包括性别、年龄、上报年份、上报国家、严重ADR）和安全警告信号。结果：收集到的6 029 375
份ADR报告中，SGLT2抑制剂为伴随和怀疑药物的ADR报告有43 807份，其中卡格列净ADR报告19 301份、达格列净ADR报告
10 960 份、恩格列净 ADR 报告 13 546 份。除性别未知和年龄缺失的 ADR 报告外，纳入报告患者的性别分布均衡，主要集中在
50～75 岁范围内，上报年份主要在 2018 年，主要上报国家为美国，以“住院或住院时间延长”为主要的严重 ADR。共挖掘得到
ADR信号573个，累及系统26个，主要集中在代谢与营养类疾病、内分泌失调、肾脏及泌尿系统疾病、感染及侵扰类疾病等方面。
卡格列净、达格列净、恩格列净ADR频数排序前10位的主要ADR信号共14个，达格列净、恩格列净的ADR信号中强度最强的信
号都依次为酮症酸中毒（PRR 值分别为 119.64、140.11，ROR 值的 95％CI 下限分别为 148.28、178.78）和真菌感染（PRR 值分别为
47.76、34.77，ROR 值的 95％CI 下限分别为 50.69、36.28）；而卡格列净除上述 2 个信号较强外，截趾（PRR 值为 489.79，ROR 值的
95％CI下限为520.15）和骨髓炎（PRR值为61.42，ROR值的95％CI下限为65.38）的信号也较强。结论：SGLT2抑制剂在代谢与营
养类疾病、内分泌失调、肾脏及泌尿系统疾病、感染及侵扰类疾病方面的安全风险较高。达格列净、卡格列净、恩格列净易引起酮
症酸中毒、真菌感染等ADR，卡格列净还易引起截趾、骨髓炎等ADR。
关键词 钠-葡萄糖共转运蛋白2抑制剂；卡格列净；达格列净；恩格列净；数据挖掘；不良事件报告系统；不良反应信号
Excavation and Evaluation of ADR Signals of SGLT2 Inhibitors
ZHENG Shufen 1，2 ，ZHONG Shilong （1. College of Pharmacy，Southern Medical University，Guangzhou
1，2
510515，China；2. Dept. of Pharmacy，Guangdong Provincial People’s Hospital，Guangzhou 510080，China）

ABSTRACT OBJECTIVE：To excavate and evaluate ADR signals of SGLT2 inhibitors as canagliflozin，dapagliflozin and
empagliflozin，and to provide reference for rational drug use in the clinic. METHODS：The proportional reporting ratio（PRR）and
reporting odds ratio （ROR） were used to find the adverse drug reactions （ADR） signal of SGLT2 inhibitors as canagliflozin，
dapagliflozin and empagliflozin from the second quarter of 2013 to the third quarter of 2020 in the US FDA Adverse Event
Reporting System（FAERS）. The basic information（including gender，age，reporting year，reporting country，severe ADR）and
safety warning signals of corresponding patients in ADR report were analyzed. RESULTS：Among 6 029 375 ADR reports，SGLT2
inhibitors of 43 807 ADR reports were concomitant and suspected drugs；there were 19 301 ADR reports of canagliflozin，10 960
ADR reports of dapagliflozin，13 546 ADR reports of empagliflozin. Except for the ADR patients with unknown gender and
missing age，the gender distribution of the included reports was balanced，mainly in the range of 50-75 years old. The reporting
year was mainly in 2018，and the main reporting country was the United States，with“hospitalization or prolonged hospitalization”
as the main serious ADR. A total of 573 ADR signals were obtained，involving 26 systems，mainly focusing on metabolic and
nutritional diseases，endocrine disorders，kidney and urinary system disease，infection and invasion diseases，etc. The results
showed that there were 14 main ADR signals in the top 10 ADR of canagliflozin，dapagliflozin and empagliflozin. The strongest
ADR signals of dapagliflozin and empagliflozin were ketoacidosis（PRR＝119.64/140.11，95％ CI lower limit of ROR＝148.28/
178.78）and fungal infection（PRR＝47.76/34.77，95％ CI lower limit of ROR＝50.69/36.28）；except above signals in addition，
toe amputation （PRR＝489.79，95％ CI lower limit of ROR＝520.15） and osteomyelitis （PRR＝61.42，95％ CI lower limit of
ROR＝65.38）were strong in the ADR signals of canagliflozin. CONCLUSIONS：SGLT2 inhibitors have a higher security risk in
metabolic and nutritional diseases，endocrine disorders，kidney and urinary system，and infection and intrusion diseases.
Dapagliflozin， canagliflozin and empagliflozin are prone to
Δ 基金项目：国家自然科学基金资助项目（No.81872934）；广东省重
cause ADR such as ketoacidosis and fungal infection，while
点领域研发计划项目“精准医学与干细胞”专项（No.2019B020229003） canagliflozin is easy to cause ADRs such as toe amputation
＊硕士研究生。研究方向：临床药理学。E-mail：2631677075@
and osteomyelitis.
qq.com
KEYWORDS SGLT2 inhibitors；Canagliflozin；Dapagliflozin；
# 通信作者：研究员，博士生导师。研究方向：临床药理学、药物
Empagliflozin； Data mining；ADR reporting system；ADR
基因组学、药物代谢。电话：020-83827812-51157。E-mail：zhongsl@
signal
hotmail.com
·986 · China Pharmacy 2021 Vol. 32 No. 8 中国药房 2021年第32卷第8期