胰高血糖素样肽-1 受体激动剂与胰腺癌风险：一项使用 FDA 不良事件报告系统和文献可视化分析的药物警戒研究。
Glucagon-like peptide 1 receptor agonists and the potential risk of pancreatic carcinoma: a pharmacovigilance study using the FDA Adverse Event Reporting System and literature visualization analysis.
机构信息
Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China.
Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.
出版信息
Int J Clin Pharm. 2023 Jun;45(3):689-697. doi: 10.1007/s11096-023-01556-2. Epub 2023 Mar 28.
BACKGROUND
There are increasing data on the potential risk of pancreatic carcinoma associated with glucagon-like peptide 1 receptor agonists (GLP-1RAs).
AIM
The study aimed to determine whether GLP-1RAs are associated with increased detection of pancreatic carcinoma based on the FDA Adverse Events Reporting System and clarify its potential mechanisms through keyword co-occurrence analysis from literature database.
METHOD
Disproportionality and Bayesian analyses were used for signal detection using reporting odds ratio (ROR), proportional reporting ratio (PRR), information component (IC), and empirical Bayesian geometric mean (EBGM). Mortality, life-threatening events, and hospitalizations were also investigated. VOSviewer was adopted to generate visual analysis of keyword hotspots.
RESULTS
A total of 3073 pancreatic carcinoma cases were related to GLP-1RAs. Five GLP-1RAs were detected with signals for pancreatic carcinoma. Liraglutide had the strongest signal detection (ROR 54.45, 95% CI 51.21-57.90; PRR 52.52, 95% CI 49.49-55.73; IC 5.59; EBGM 48.30). The signals of exenatide (ROR 37.32, 95% CI 35.47-39.28; PRR 36.45, 95% CI 34.67-38.32; IC 5.00; EBGM 32.10) and lixisenatide (ROR 37.07, 95% CI 9.09-151.09; PRR 36.09; 95% CI 9.20-141.64; IC 5.17, EBGM 36.09) were stronger than those of semaglutide (ROR 7.43, 95% CI 5.22-10.57; PRR 7.39; 95% CI 5.20-10.50; IC 2.88, EBGM 7.38) and dulaglutide (ROR 6.47, 95% CI 5.56-7.54; PRR 6.45; 95% CI 5.54-7.51; IC 2.67, EBGM 6.38). The highest mortality rate occurred in exenatide (63.6%). Based on the bibliometric investigation, cAMP/protein-kinase, Ca channel, endoplasmic-reticulum stress, and oxidative stress are potential pathogenesis of pancreatic carcinoma resulting from GLP-1RAs.
CONCLUSION
Based on this pharmacovigilance study, GLP-1RAs, except albiglutide, are associated with pancreatic carcinoma.
背景
越来越多的数据表明，胰高血糖素样肽 1 受体激动剂（GLP-1RAs）与胰腺癌的潜在风险相关。
目的
本研究旨在通过美国食品药品监督管理局不良事件报告系统确定 GLP-1RAs 是否与胰腺癌的检出率增加相关，并通过文献数据库中的关键词共现分析阐明其潜在机制。
方法
采用报告比值比（ROR）、比例报告比（PRR）、信息成分（IC）和经验贝叶斯几何均值（EBGM）进行比例失衡和贝叶斯分析以检测信号。还调查了死亡率、危及生命的事件和住院情况。采用 Vosviewer 生成关键词热点的可视化分析。
结果
共发现 3073 例与 GLP-1RAs 相关的胰腺癌病例。五种 GLP-1RAs 被检测到与胰腺癌有信号关联。利拉鲁肽的信号检测最强（ROR 54.45，95%CI 51.21-57.90；PRR 52.52，95%CI 49.49-55.73；IC 5.59；EBGM 48.30）。艾塞那肽（ROR 37.32，95%CI 35.47-39.28；PRR 36.45，95%CI 34.67-38.32；IC 5.00；EBGM 32.10）和利西那肽（ROR 37.07，95%CI 9.09-151.09；PRR 36.09；95%CI 9.20-141.64；IC 5.17，EBGM 36.09）的信号强于司美格鲁肽（ROR 7.43，95%CI 5.22-10.57；PRR 7.39；95%CI 5.20-10.50；IC 2.88，EBGM 7.38）和度拉糖肽（ROR 6.47，95%CI 5.56-7.54；PRR 6.45；95%CI 5.54-7.51；IC 2.67，EBGM 6.38）。艾塞那肽的死亡率最高（63.6%）。基于文献计量学调查，cAMP/蛋白激酶、钙通道、内质网应激和氧化应激是 GLP-1RAs 导致胰腺癌的潜在发病机制。
结论
基于这项药物警戒研究，除了阿必鲁肽外，GLP-1RAs 与胰腺癌相关。
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