The Zucker Hillside Hospital, Department of Psychiatry, Northwell Health, Glen Oaks, New York.
Department of Psychiatry, Zucker School of Medicine at Northwell/Hofstra, Hempstead, Glen Oaks, New York.
JAMA Netw Open. 2024 Aug 1;7(8):e2423385. doi: 10.1001/jamanetworkopen.2024.23385.
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have gained use primarily due to their weight-reduction effects, although a regulatory review was undertaken for potential suicidality concern.
To evaluate potential signals for suicidal and self-injurious adverse drug reactions (ADRs) associated with the GLP-1 RAs semaglutide and liraglutide.
DESIGN, SETTING, AND PARTICIPANTS: Disproportionality analysis through the case-control design using the World Health Organization (WHO) global database of suspected ADRs. Participants were clinical patients worldwide experiencing an ADR suspectedly attributable to semaglutide or liraglutide in the database from inception to August 30, 2023. Data were analyzed from September to December 2023.
Treatment with semaglutide or liraglutide regardless of indication or treatment duration.
Reporting odds ratio (ROR) and the bayesian information component (IC) with 95% CIs were calculated as measures of disproportionate reporting of suicidal and self-injurious ADRs associated with semaglutide and liraglutide compared with all other medications. Sensitivity analyses were conducted including patients with coreported use of antidepressants and benzodiazepines and using dapagliflozin, metformin, and orlistat as comparators. A disproportionality signal was considered when the lower limits of the ROR and IC were above 1 and 0, respectively.
A total of 107 (median [IQR] age 48 [40-56] years; 59 female patients [55%]) and 162 (median [IQR] age 47 [38-60] years; 100 female patients [61%]) cases of suicidal and/or self-injurious ADRs were reported between November 2000 and August 2023 with semaglutide and liraglutide, respectively. Significant disproportionality was detected only for semaglutide-associated suicidal ideation (ROR, 1.45; 95% CI, 1.18-1.77; IC, 0.53; 95% CI, 0.19-0.78), which remained significant in patients with coreported use of antidepressants (ROR, 4.45; 95% CI, 2.52-7.86; IC, 1.96; 95% CI, 0.98-2.63) and benzodiazepines (ROR, 4.07; 95% CI, 1.69-9.82; IC, 1.67; 95% CI, 0.11-2.65), when compared with dapagliflozin (ROR, 5.56; 95% CI, 3.23-9.60; IC, 0.70; 95% CI, 0.36-0.95), metformin (ROR, 3.86; 95% CI, 2.91-5.12; IC, 1.20; 95% CI, 0.94-1.53) and orlistat (ROR, 4.24; 95% CI, 2.69-6.69; IC, 0.70; 95% CI, 0.36-0.95).
This study using the WHO database found a signal of semaglutide-associated suicidal ideation, which warrants urgent clarification.
胰高血糖素样肽-1 受体激动剂 (GLP-1 RAs) 主要因其减重效果而被广泛使用，尽管对其潜在自杀风险进行了监管审查。
评估与 GLP-1 RAs 司美格鲁肽和利拉鲁肽相关的自杀和自伤药物不良反应 (ADR) 的潜在信号。
设计、地点和参与者：通过病例对照设计进行的不寻常性分析，使用世界卫生组织 (WHO) 的疑似 ADR 全球数据库。参与者为全球临床患者，在数据库中自 2000 年 11 月至 2023 年 8 月 30 日期间因疑似归因于司美格鲁肽或利拉鲁肽的 ADR 而接受治疗。数据于 2023 年 9 月至 12 月进行分析。
无论指示或治疗持续时间如何，使用司美格鲁肽或利拉鲁肽治疗。
计算报告比值比 (ROR) 和贝叶斯信息分量 (IC) 及其 95%可信区间，作为与所有其他药物相比，与司美格鲁肽和利拉鲁肽相关的自杀和自伤 ADR 报告不寻常性的衡量标准。进行了敏感性分析，包括同时报告使用抗抑郁药和苯二氮䓬类药物的患者，以及使用达格列净、二甲双胍和奥利司他作为对照。当 ROR 和 IC 的下限分别高于 1 和 0 时，认为存在不寻常性信号。
分别于 2000 年 11 月至 2023 年 8 月期间，在司美格鲁肽和利拉鲁肽的治疗中报告了 107 例 (中位数 [IQR] 年龄 48 [40-56] 岁；59 例女性患者 [55%]) 和 162 例 (中位数 [IQR] 年龄 47 [38-60] 岁；100 例女性患者 [61%]) 自杀和/或自伤 ADR。仅发现司美格鲁肽相关自杀意念存在显著的不寻常性 (ROR，1.45；95%CI，1.18-1.77；IC，0.53；95%CI，0.19-0.78)，在同时报告使用抗抑郁药和苯二氮䓬类药物的患者中仍然显著 (ROR，4.45；95%CI，2.52-7.86；IC，1.96；95%CI，0.98-2.63) 和苯二氮䓬类药物 (ROR，4.07；95%CI，1.69-9.82；IC，1.67；95%CI，0.11-2.65)，与达格列净 (ROR，5.56；95%CI，3.23-9.60；IC，0.70；95%CI，0.36-0.95)、二甲双胍 (ROR，3.86；95%CI，2.91-5.12；IC，1.20；95%CI，0.94-1.53) 和奥利司他 (ROR，4.24；95%CI，2.69-6.69；IC，0.70；95%CI，0.36-0.95) 相比。
本研究使用世界卫生组织数据库发现了司美格鲁肽相关自杀意念的信号，这需要紧急澄清。
