Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada; Brain and Cognition Discovery Foundation, Toronto, Ontario, Canada.
Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
J Affect Disord. 2025 Jan 15;369:922-927. doi: 10.1016/j.jad.2024.10.062. Epub 2024 Oct 19.
Reports of suicidality associated with glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have been reported to the European Medicines Agency (EMA) and the United States Food and Drug Administration (FDA). We previously reported an increased reporting odds ratio (ROR) of some measures of suicidality with semaglutide and liraglutide using the FDA Adverse Event Reporting System (FAERS). Notwithstanding the increased ROR, causality between GLP-1 RAs exposure and any aspect of suicidality is not established.
The analysis herein aims to extend a previous analysis of the FAERS by evaluating the ROR for suicidality reported to the World Health Organization (WHO) Pharmacovigilance Database (VigiBase). We aimed to characterize the ROR of suicidality associated with GLP-1 RAs, as extrapolated from spontaneous reports. As per our previous report, the ROR was considered significant when the lower limit of the 95 % confidence (CI) was >1.0.
We searched VigiBase reports from inception to January 2024. The RORs for suicidal ideation were significantly increased for semaglutide (5.82), liraglutide (4.03) and tirzepatide (2.25). For "depression/suicidal", the ROR was significantly increased for semaglutide (14.74) and liraglutide (5.86); and for suicidal behaviour, the ROR was significantly increased for semaglutide (6.52) and liraglutide (3.90). However, for suicide attempts, the ROR was significantly decreased for semaglutide (0.11), dulaglutide (0.075), exenatide (0.047) and liraglutide (0.15). For completed suicide, the ROR was also significantly decreased for semaglutide (0.01), dulaglutide (0.003), exenatide (0.002) and liraglutide (0.008).
Unlike our previous report with FAERS, a mixed pattern of ROR emerged in the WHO VigiBase with respect to suicidality and exposure to select GLP-RAs. Causation between GLP-1 RA exposure and suicidality (either increased or decreased) cannot be ascertained from ROR data.
GLP-1 受体激动剂（GLP-1 RAs）与自杀意念相关的报告已向欧洲药品管理局（EMA）和美国食品和药物管理局（FDA）报告。我们之前曾报告，使用 FDA 不良事件报告系统（FAERS），一些与司美格鲁肽和利拉鲁肽相关的自杀意念指标的报告比值比（ROR）增加。尽管 ROR 增加，但 GLP-1 RAs 暴露与自杀意念的任何方面之间的因果关系尚未确定。
本分析旨在通过评估向世界卫生组织（WHO）药物警戒数据库（VigiBase）报告的自杀意念的 ROR，扩展之前对 FAERS 的分析。我们旨在从自发报告中推断出与 GLP-1 RAs 相关的自杀意念的 ROR，以描述其特征。根据我们之前的报告，当 95%置信区间（CI）的下限>1.0 时，ROR 被认为具有统计学意义。
我们从成立到 2024 年 1 月搜索了 VigiBase 报告。司美格鲁肽（5.82）、利拉鲁肽（4.03）和替西帕肽（2.25）的自杀意念 ROR 显著增加。对于“抑郁/自杀”，司美格鲁肽（14.74）和利拉鲁肽（5.86）的 ROR 显著增加；对于自杀行为，司美格鲁肽（6.52）和利拉鲁肽（3.90）的 ROR 显著增加。然而，对于自杀企图，司美格鲁肽（0.11）、度拉糖肽（0.075）、艾塞那肽（0.047）和利拉鲁肽（0.15）的 ROR 显著降低。对于完成自杀，司美格鲁肽（0.01）、度拉糖肽（0.003）、艾塞那肽（0.002）和利拉鲁肽（0.008）的 ROR 也显著降低。
与我们之前使用 FAERS 的报告不同，在 WHO VigiBase 中，关于自杀意念和暴露于某些 GLP-RAs 的 ROR 出现了混合模式。不能从 ROR 数据确定 GLP-1 RA 暴露与自杀意念（增加或减少）之间的因果关系。
