顺式孟德尔随机化联合美国FAERS数据库分析胰高血糖素样肽-1受体激动剂的胰腺不良事件信号

doi:10.19803/j.1672-8629.20250284

摘要/Abstract

摘要： 目的使用孟德尔随机化（MR）探究胰高血糖素样肽-1（GLP-1）受体激动剂（GLP-1RA）类药品与胰腺相关不良事件（AE）的因果关系,并检索2018年1月1日至2024年9月30日美国食品药品监督管理局（FDA）不良事件报告系统（FAERS）数据库对存在因果关联的AE进行信号挖掘。方法使用逆方差加权法作为MR的主要分析方法,使用卡方检验和3种不相称分析方法联合挖掘AE信号。结果 GLP-1RA类药品与急性胰腺炎（OR=1.003,95%CI：1.002～1.004,P＜0.000 1）、慢性胰腺炎（OR=1.434,95%CI：1.231～1.670,P＜0.000 1）存在因果关联,与胰腺癌（ORBI-DDBJ=1.444,95%CI：0.818～1.222,P=2.549；ORMRC-IEU=0.856,95%CI：0.294～2.497,P=0.776 5）不存在因果关联。在FAERS数据库中选取5种临床常用的GLP-1RA药品并得到AE报告11 261 704例,产生与胰腺炎相关的AE信号共10种。分层分析发现,AE信号主要集中在45～64岁、65岁以上2个年龄段,且各年龄段的AE较为接近。杜拉鲁肽、艾塞那肽、利司那肽3种药品在男性和女性中产生的信号AE相同。结论 GLP-1RA类药品可能增加胰腺炎发病风险而不增加胰腺癌发病风险。FAERS信号挖掘显示出不同GLP-1RA药品胰腺炎相关AE特点,为临床安全用药提供参考。

关键词: 胰高血糖素样肽-1受体激动剂, 孟德尔随机化, 美国FDA不良事件报告系统, 药品不良反应, 信号挖掘, 胰腺炎

Abstract: Objective To investigate the causal relationship between GLP-1RA medications and pancreatic-related adverse event (AE) using Mendelian randomization (MR) before mining AE signals for causal AE using the FDA Adverse Event Reporting System (FAERS) database from 1 Jan, 2018 to 30 Sep, 2024. Methods The inverse variance weighting method was used as the primary analysis method for MR. Chi-square test and three disproportionality analysis methods were combined to mine AE signals. Results GLP-1RA medications were found to have causal associations with acute pancreatitis (OR=1.003, 95%CI:1.002–1.004, P＜0.000 1) and chronic pancreatitis (OR=1.434, 95%CI:1.231–1.670, P＜0.000 1). No causal associations were found with pancreatic cancer (ORBI-DDBJ=1.444, 95%CI:0.818–1.222, P=2.549; ORMRC-IEU=0.856, 95%CI: 0.294–2.497, P=0.776 5). In the FAERS database, 11 261 704 AE reports were obtained from five clinically commonly used GLP-1RA medications, and 10 types of AE signals related to pancreatitis were identified. Stratified analysis revealed that AE signals primarily involved groups ages 45 to 64 and ages 65 and older, with similar types of AE across these age groups. For dulaglutide, exenatide and liraglutide, the types of signal AE were the same in both male and female stratum. Conclusion GLP-1RA medications can increase the risk of pancreatitis rather than pancreatic cancer. Signal mining of the FAERS data reveals the characteristics of pancreatitis-related AE associated with different GLP-1RA medications.

Key words: Glucagon-Like Peptide-1 Receptor Agonist (GLP-1RA), Mendelian Randomization, FDA Adverse Event Reporting System (FAERS), Adverse Drug Reaction, Data Mining, Pancreatitis

中图分类号:

R977
R994.11

李月, 郭晓晶, 吴波, 潘婷婷, 王砚青, 陶文慧. 顺式孟德尔随机化联合美国FAERS数据库分析胰高血糖素样肽-1受体激动剂的胰腺不良事件信号[J]. 中国药物警戒, 2025, 22(12): 1418-1423.

LI Yue, GUO Xiaojing, WU Bo, PAN Tingting, WANG Yanqing, TAO Wenhui. Pancreatic Adverse Effect of Glucagon-Like Peptide-1 Receptor Agonist Based on cis Mendelian Randomization and US FAERS Database[J]. Chinese Journal of Pharmacovigilance, 2025, 22(12): 1418-1423.

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https://zgywjj.magtechjournal.com/CN/Y2025/V22/I12/1418

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