中国药物警戒 ›› 2025, Vol. 22 ›› Issue (6): 669-673.
DOI: 10.19803/j.1672-8629.20241041

• 安全与合理用药 • 上一篇    下一篇

基于美国FAERS数据库的替尔泊肽胰腺相关不良事件信号分析

景天舒1, 路国涛2,3#, 王胜锋1*   

  1. 1北京大学公共卫生学院流行病与统计学系,重大疾病流行病学教育部重点实验室,北京 100191;
    2扬州大学附属医院消化内科,江苏 扬州 225012;
    3扬州大学护理学院公共卫生学院,江苏 扬州 225009
  • 收稿日期:2024-12-26 出版日期:2025-06-15 发布日期:2025-06-18
  • 通讯作者: *王胜锋,男,博士,研究员·博导,药物流行病、真实世界数据分析和大数据建模。E-mail: wangshengfeng@bjmu.edu.cn;#为共同通信作者。
  • 作者简介:景天舒,男,在读硕士,公共卫生学。
  • 基金资助:
    国家自然科学基金资助项目（82173616）

Risks of Pancreatic Adverse Events Associated with Tirzepatide: a Disproportionality Analysis Using Spontaneous Adverse Event Reporting System Data

JING Tianshu1, LU Guotao2,3#, WANG Shengfeng1*   

  1. 1Peking University School of Public Health, Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing 100191, China;
    2Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou Jiangsu 225012, China;
    3School of Nursing, School of Public Health, Yangzhou University, Yangzhou Jiangsu 225009, China
  • Received:2024-12-26 Online:2025-06-15 Published:2025-06-18

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摘要： 目的 评估替尔泊肽不良事件风险,比较替尔泊肽与其他已上市胰高血糖素样肽-1（GLP-1）类药物的胰腺安全性。方法 采用美国食品药品监督管理局不良事件报告系统（FAERS）（2004年第1季度至2024年第3季度）进行不良事件信号挖掘,并用日本药品不良事件报告数据库（JADER）（2009年1月1日至2023年12月31日）进行信号验证。采用比例失衡法挖掘替尔泊肽的不良事件信号,并比较替尔泊肽与其他GLP-1受体激动剂药物之间的信号强度。通过对适应证、不良事件诱发时间（TTO）及敏感性分析,消除适应证与不良事件关联及替尔泊肽不良事件积累时间不足可能导致的混杂因素。结果 替尔泊肽存在显著的胰腺炎（ROR=7.80, 95%CI:7.07~8.61）不良事件风险信号。通过敏感性分析控制适应证与不良事件之间的潜在混杂后,替尔泊肽仍存在胰腺炎的阳性信号。基于美国FAERS数据库的结果,与替尔泊肽相比,其他GLP-1受体激动剂的胰腺炎风险更高,包括司美格鲁肽（ROR=2.04, 95%CI:1.82~2.30）、利拉鲁肽（ROR=4.76, 95%CI:4.34~5.22）和度拉糖肽（ROR=2.01, 95%CI:1.82~2.21）。结论 替尔泊肽可能增加胰腺炎风险,但与其他GLP-1受体激动剂相比,其胰腺炎及其他胰腺不良事件的风险较低。提示临床使用中,无论是选择GLP-1受体激动剂药物还是使用替尔泊肽,都需关注其可能的胰腺不良事件。

关键词: 替尔泊肽, 司美格鲁肽, 胰高血糖素样肽-1受体激动剂, 2型糖尿病, 胰腺炎, 药品不良事件, 美国食品药品监督管理局不良事件报告系统

Abstract: Objective To evaluate risks of pancreatic adverse events (AEs) caused by a newly marketed glucagon-like peptide-1 (GLP-1) receptor and glucose-dependent insulinotropic polypeptide (GIP) receptor dual target agonist, tirzepatide, and to compare the pancreatic safety of tirzepatide with other previously marketed GLP-1 drugs. Methods Data from the FDA Adverse Event Reporting System (FAERS) was used for signal mining of AEs from first quarter of 2004 to third quarter of 2024 while the Japanese Adverse Drug Event Report Database (JADER) was searched for validation of signals from 2009 to 2023. All the data used in this study was released as of the third quarter of 2024. Disproportionality analysis was used to detect AE signals of tirzepatide and compare tirzepatide with other GLP-1RA drugs. Sensitivity analyses were conducted of indications and time-to-onset (TTO) to eliminate potential confounding caused by association between AE and indications, and insufficient AE accumulation time of tirzepatide. Results Tirzepatide showed significant risk signals for pancreatitis (ROR=7.80, 95%CI: 7.07-8.61) and pancreatic necrosis (ROR=3.76, 95%CI: 2.06-6.85). After the association between indications and AEs through sensitivity analysis was controlled, tirzepatide showed positive signals for pancreatitis (ROR=2.74, 95%CI: 2.16-3.47). Higher risks of pancreatitis were associated with semaglutide (ROR=2.04, 95%CI: 1.82-2.30), liraglutide (ROR=4.76, 95%CI: 4.34-5.22) and dulaglutide (ROR=2.01, 95%CI: 1.82-2.21). Conclusion sThe analysis of spontaneous AE reports suggests that tirzepatide can increase the risk of pancreatitis, but the chances are smaller compared with other GLP-1 receptor agonists. When tirzepatide is used clinically or GLP-1RA medications are opted for, clinicians ought to be alert to pancreatic adverse events.

Key words: Tirzepatide, Semaglutide, Glucagon-Like Peptide-1 Receptor Agonists, Type 2 Diabetes Mellitus, Pancreatitis, Adverse Drug Events, FAERS

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