| 摘要: |
| 目的 利用美国FDA不良事件报告系统（FAERS）对钠-葡萄糖共转运蛋白2（SGLT2）抑制剂的生殖系统药物毒性进行全面分析，挖掘潜在的生殖系统不良事件信号，以期为临床合理用药提供参考。方法 采用压缩估计的不相称测定分析，选取报告比值比法（ROR）和成分信息法（IC）对FAERS中2013年第1季度至2021年第2季度有关SGLT2抑制剂的数据进行挖掘，借助重要医疗事件（IME）列表筛选出生殖系统IME。所有的不良事件及IME均由《国际医学用语词典》（MedDRA）24.0版编码。分析患者的临床特征、预后、信号检测结果及指定不良事件的事件发生时间（TTO）。结果 将SGLT2抑制剂作为“首要怀疑”和“次要怀疑”的生殖系统不良事件报告纳入分析，共获得2 700条记录。男性生殖系统不良事件发生频率（57.59%，1 555/2 700）高于女性（35.70%，964/2 700），单药治疗与生殖不良事件的关联强度高于联合用药（IC的95% CI下限：1.40 vs 1.21；ROR的95% CI下限：2.65 vs 2.37）。在单药治疗中共检测出56个信号，出现8个强信号和13个IME。常见的生殖系统不良事件是Fournier坏疽、生殖器真菌感染、龟头包皮炎等。说明书中未提及的IME共10个，包括男性外生殖器蜂窝织炎、乳腺癌、阴茎癌等。结论 除了已知的生殖系统不良事件，SGLT2抑制剂还存在其他重要的生殖系统不良事件信号。不同SGLT2抑制剂的生殖毒性存在差异性，临床医师应充分考量用药的风险与收益，对严重不良事件进行重点监测。 |
| 关键词: 钠-葡萄糖共转运蛋白2抑制剂 生殖毒性 不良事件 美国FDA不良事件报告系统 不相称测定分析 |
| DOI：10.16781/j.CN31-2187/R.20210892 |
| 投稿时间：2021-09-08修订日期：2022-11-10 |
| 基金项目:国家自然科学基金（82073671），上海市公共卫生体系建设三年行动计划学科带头人计划（GWV-10.2-XD22），上海市卫生和计划生育委员会优秀青年医学人才培养计划（2018YQ47），上海市公共卫生体系建设三年行动计划优青计划（GWV-10.2-YQ33），上海市公共卫生体系建设三年行动计划学科建设项目"大数据与人工智能应用"（GWV-10.1-XK05），军队双重建设项目-03. |
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| Reproductive toxicity of SGLT2 inhibitors: signal mining and analysis based on the US Food and Drug Administration Adverse Event Reporting System |
| XU Xiao1,YE Xiao-fei2,ZHOU Xiang1,LIU Dong-xu1,DONG Zi-wei1,HE Jia1,2* |
(1. School of Medicine, Tongji University, Shanghai 200092, China;
2. Department of Military Health Statistics, Faculty of Medical Services, Naval Medical University (Second Military Medical University), Shanghai 200433, China
*Corresponding author) |
| Abstract: |
| Objective To conduct a comprehensive analysis on the reproductive toxicity of sodium-glucose co-transporter 2 (SGLT2) inhibitors and to uncover the potential signals based on the US Food and Drug Administration Adverse Event Reporting System (FAERS), hoping to provide references for rational clinical drug use. Methods We selected the data from the first quarter of 2013 to the second quarter of 2021 in FAERS to conduct disproportionality analysis. Two approaches, based on statistical shrinkage transform, reported odds ratio (ROR) and information component (IC), were used to evaluate the correlation between SGLT2 inhibitors and reproductive adverse events (AEs). Based on the important medical event (IME) list, we screened the IMEs of reproduction. The definition of AEs and IMEs relied on the preferred terms by the Medical Dictionary for Regulatory Activities (MedDRA) version 24.0. The clinical characteristics of patients, prognosis, signal detection results and time to onset (TTO) for specified AEs were analyzed. Results A total of 2 700 records of reproductive AEs were associated with SGLT2 inhibitors, with "primary suspect" and "secondary suspect" used as filters. In general, males were more prone to reproductive AEs, with a much higher proportion than females (57.59%[1 555/2 700]vs 35.70%[964/2 700]). Monotherapy (IC025:1.40; ROR025:2.65) was associated with a higher strength of reproductive AEs than the combination (IC025:1.21; ROR025:2.37). In monotherapy, a total of 56 signals were detected, with 8 strong signals and 13 IMEs. The common reproductive AEs included Fournier's gangrene, genital infection fungal, and balanoposthitis. There were 10 IMEs which were not mentioned in the instructions, including male external genital cellulitis, breast cancer, and penile cancer. Conclusion In addition to the known reproductive AEs, there remain other important reproductive signals of SGLT2 inhibitors. The reproductive toxicity varies among SGLT2 inhibitors, and clinicians should be reminded to fully consider the risk-benefit balance and prioritize IMEs for surveillance. |
| Key words: sodium-glucose co-transporter 2 inhibitors reproductive toxicity adverse events Food and Drug Administration Adverse Event Reporting System disproportionality analysis |
