Kim Tae Hyeon, Lee Kyeongmin, Park Seoyoung, Oh Jiyeon, Park Jaeyu, Jo Hyesu, Lee Hayeon, Cho Jaehyeong, Wen Xuerong, Cho Hanseul, Kim Sunyoung, Yon Dong Keon
Center for Digital Health, Medical Science Research Institute, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, South Korea.
Department of Medicine, Kyung Hee University College of Medicine, Seoul, South Korea.
Diabetes Obes Metab. 2025 Jun;27(6):3490-3502. doi: 10.1111/dom.16376. Epub 2025 Apr 2.
This study aims to compare adverse drug reaction patterns of liraglutide, semaglutide and tirzepatide-glucagon-like peptide-1 receptor agonists (GLP-1 RAs) approved for anti-obesity medications-to evaluate their real-world safety.
This disproportionality analysis utilized a case-control design with VigiBase. The study focused on reports of adverse events associated with liraglutide, semaglutide and tirzepatide, selected based on warnings in the US Food and Drug Administration approval labels for each drug. Data were restructured using unique identifiers to differentiate individuals affected by adverse drug reactions. Multivariable logistic regression models estimated adjusted reporting odds ratios (aRORs) with 95% confidence intervals (CIs) to assess the association between various adverse events and GLP-1 RAs, adjusting for age, sex, region, reporter qualification, reporting year and concomitant medication. The information component (IC) was analysed, and signals of adverse drug reactions were considered significant only when both aROR and IC were statistically significant.
Our analysis of targeted adverse drug reactions included 24 725 individuals using liraglutide, 21 454 using semaglutide and 11 538 using tirzepatide. Tirzepatide had fewer reports of adverse drug reactions compared with the other two drugs, and its pharmacovigilance association strength was the lowest. Semaglutide, however, was significantly associated with several unusual adverse events, including suicidal ideation and behaviour (IC, 1.53 [IC, 1.28]; aROR, 2.52 [95% CI, 2.18-2.93]), hair loss (IC, 0.78 [IC, 0.63]; aROR, 1.42 [95% CI, 1.30-1.55]) and vision loss (IC, 1.27 [IC, 1.13]; aROR, 1.80 [95% CI, 1.66-1.97]).
Our findings emphasize the need for cautious prescribing and further research to ensure the safe use of these medications.
本研究旨在比较已获批用于抗肥胖治疗的利拉鲁肽、司美格鲁肽和替尔泊肽这三种胰高血糖素样肽-1受体激动剂（GLP-1 RAs）的药物不良反应模式，以评估它们在现实世界中的安全性。
本不成比例分析采用与药物不良反应数据库（VigiBase）的病例对照设计。该研究聚焦于与利拉鲁肽、司美格鲁肽和替尔泊肽相关的不良事件报告，这些报告是根据美国食品药品监督管理局对每种药物批准标签中的警示信息挑选出来的。利用唯一标识符对数据进行重组，以区分受药物不良反应影响的个体。多变量逻辑回归模型估计调整后的报告比值比（aRORs）及95%置信区间（CIs），以评估各种不良事件与GLP-1 RAs之间的关联，并对年龄、性别、地区、报告者资质、报告年份及合并用药进行校正。分析信息成分（IC），仅当aROR和IC均具有统计学意义时，药物不良反应信号才被视为显著。
我们对目标药物不良反应的分析纳入了24725例使用利拉鲁肽的个体、21454例使用司美格鲁肽的个体和11538例使用替尔泊肽的个体。与其他两种药物相比，替尔泊肽的药物不良反应报告较少，其药物警戒关联强度最低。然而，司美格鲁肽与一些不常见的不良事件显著相关，包括自杀意念和行为（IC，1.53[IC，1.28]；aROR，2.52[95%CI，2.18 - 2.93]）、脱发（IC，0.78[IC，0.63]；aROR，1.42[95%CI，1.30 - 1.55]）和视力丧失（IC，1.27[IC，1.13]；aROR，1.80[95%CI，1.66 - 1.97]）。
我们的研究结果强调谨慎开药及进一步研究以确保这些药物安全使用的必要性。
