基于FAERS数据库的GLP-1RA的药物不良反应研究

Research on Adverse Drug Reactions of GLP-1RA Based on FAERS Database

关键词:  胰高血糖素样肽-1受体激动剂  药物不良反应信号  FAERS数据库  药物警戒

Key words:  glucagon-like peptide-1 receptor agonist  adverse drug reaction signals  FAERS database  pharmacovigilance

摘要:

目的 利用美国FDA不良事件报告系统(FAERS)分析挖掘6种胰高血糖素样肽-1受体激动剂(GLP-1RA)的不良反应(ADR)信号及说明书外的风险信号,为临床合理用药提供参考。方法 使用在线工具Open Vigil 2.1检索2004年第一季度~2023年第三季度上报到美国FAERS数据库的药品不良反应事件(ADE)报告,以《监管活动医学词典》(MedDRA)中的首选语(PT)编码并汉化药物ADE,采取比例失衡法进行信号挖掘,筛选ADR信号并做统计分析。结果 分别检索到艾塞那肽、利拉鲁肽、度拉糖肽、利司那肽、替西帕肽、司美格鲁肽的ADE报告61495、24553、53846、1985、20330、18961份,女性占比均多于男性,报告国家主要为美国、英国、法国、日本。艾塞那肽和利司那肽发生例数最多的ADR信号为血糖升高；利拉鲁肽和司美格鲁肽发生例数最多的ADR信号为恶心；替西帕肽和度拉糖肽发生例数最多的ADR信号为注射部位疼痛。此外,6种药物中利拉鲁肽引发胰腺炎的信号强度最大(PRR=25.149)。检出率较低的胃肠道ADR信号为上腹痛和腹部不适,其中利司那肽胃肠道ADR信号检出率最低。结论 利用FAERS数据库检索6种GLP-1RA上市以来的ADR信号可为临床安全用药提供依据,为提高患者服药依从性,需重点关注胃肠道不良反应,同时应密切关注新的风险信号,如血糖升高、体重增加等。

Abstract:

ABSTRACT Objective To analyze and mine adverse drug reaction (ADR) signals of six glucagon-like peptide-1 receptor agonists (GLP-1RA) and their risk signals out of description based on the U.S. FDA Adverse Event Reporting System (FAERS), and to provide a reference for the rational use of clinical medication. Methods We used the online tool Open Vigil 2.1 to search for adverse drug event (ADE) reports for six drugs, exenatide, liraglutide, dulaglutide, lixisenatide, tirzepatide, and semaglutide, reported to the FAERS database from the first quarter of 2004 to the third quarter of 2023. The ADE is coded and translated into Chinese by the preferred term (PT) in the "Medical Dictionary of Regulatory Activities"(MedDRA). Then we adopted the proportional imbalance method for signal mining so as to screen and analyze the adverse drug reaction (ADR) signals. Results We retrieved 61,495, 24,553, 53,846, 1,985, 20,330, and 18,961 ADE reports for exenatide, liraglutide, dulaglutide, lixisenatide, tirzepatide, and semaglutide respectively. Female patients accounts for a higher proportion than male patients ,The number of female patients experiencing adverse reactions to taking tirzepatide is four times that of males, while the number of other medications is often twice as high. In terms of age composition of adverse event reports, patients aged 18 to 60 years old have a similar proportion to elderly patients aged over 60 years old, excluding tirzepatide (the former is four times higher than the latter) . The reports are mainly from the United States, the United Kingdom, France and Japan. Elevated blood sugar is the most common ADR signal for exenatide and lixisenatide. Liraglutide and semaglutide mainly focused on Nausea. The ADR signal with the highest number of cases of tirzepatide and dulaglutide is pain at the injection site. In addition, the signal intensity of liraglutide induced pancreatitis is the highest among the six drugs (PRR=25.149). The gastrointestinal ADRs with lower case detection rate are epigastric pain and abdominal discomfort, and lixisenatide has the lowest gastrointestinal ADR detection rate. Conclusion The mining of six GLP-1RAs post-marketing ADR signals based on FAERS database can provide a basis for clinical medication safety. The gastrointestinal adverse reactions should be closely monitored to improve patients' medication compliance. In addition, there is a strong association between GLP-1RA and pancreatitis, which suggests that when using GLP-1RA clinically, it is important to focus on patients who experience sudden upper abdominal pain during treatment to ensure their medication safety. Meanwhile, more attention should be paid to the new risk signals, such as elevated blood sugar, weight gain, etc.