Bezin Julien, Bénard-Laribière Anne, Hucteau Emilie, Tournier Marie, Montastruc François, Pariente Antoine, Faillie Jean-Luc
University Bordeaux, INSERM, BPH, Team AHeaD, U1219, F-33000, Bordeaux, France.
CHU de Bordeaux, Clinical Pharmacology Unit, INSERM, U1219, F-33000, Bordeaux, France.
EClinicalMedicine. 2024 Dec 31;80:103029. doi: 10.1016/j.eclinm.2024.103029. eCollection 2025 Feb.
Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are extensively evaluated for the risk of suicidal behaviors or ideation; the influence of psychiatric history or obesity on this potential effect remains to be investigated. Therefore, we aimed to assess the association between GLP-1 RA and suicide or suicide attempt, considering these factors.
Patients ≥18 y who died by suicide or were hospitalized for suicide attempt (2013-2021) with at least one GLP-1 RA dispensing within the 180 preceding days were selected from the French National Health Data System (SNDS). A case-time-control design compared, for each patient, GLP-1 RA exposure in the 30 days preceding the outcome (composite of suicide or suicide attempt) to three earlier 30-day reference periods. Potential exposure trend bias was controlled using up to five time-controls matched on age, sex, psychiatric history, obesity, calendar time. Analyses were adjusted for time-varying confounders. Finally dipeptidyl peptidase-4 (DPP-4) inhibitors were studied as negative controls for potential biases.
This study included 1102 cases and 5494 controls. Mean case age was 57.4 years (SD 11.4); 44.6% were male, 67.6% had a recent psychiatric history and 51.3% had obesity. GLP-1 RA use was not associated with an increased risk of suicide or suicide attempt (OR, 0.62; 95% CI, 0.51-0.75), with consistent results for DPP-4 inhibitors (0.75; 0.67-0.84). Results obtained according to recent psychiatric history and obesity were comparable.
This large nationwide case-time-control study provides reassurance about the short-term psychiatric safety of GLP-1 RA, showing no specific risk for patients with psychiatric disorders or obesity.
French Medicines Agency.
胰高血糖素样肽-1受体激动剂（GLP-1 RA）已针对自杀行为或自杀意念风险进行了广泛评估；精神病史或肥胖对这种潜在影响的作用仍有待研究。因此，我们旨在考虑这些因素，评估GLP-1 RA与自杀或自杀未遂之间的关联。
从法国国家卫生数据系统（SNDS）中选取2013年至2021年间因自杀死亡或因自杀未遂住院的18岁及以上患者，这些患者在结局（自杀或自杀未遂的综合情况）前180天内至少有一次GLP-1 RA配药记录。采用病例-时间-对照设计，将每位患者在结局前30天（自杀或自杀未遂的综合情况）的GLP-1 RA暴露情况与三个更早的30天参考期进行比较。使用多达五个在年龄、性别、精神病史、肥胖、日历时间上匹配的时间对照来控制潜在的暴露趋势偏差。分析针对随时间变化的混杂因素进行了调整。最后，将二肽基肽酶-4（DPP-4）抑制剂作为潜在偏差的阴性对照进行研究。
本研究纳入了1102例病例和5494例对照。病例的平均年龄为57.4岁（标准差11.4）；44.6%为男性，67.6%有近期精神病史，51.3%有肥胖症。使用GLP-1 RA与自杀或自杀未遂风险增加无关（比值比，0.62；95%置信区间，0.51 - 0.75），DPP-4抑制剂的结果一致（0.75；0.67 - 0.84）。根据近期精神病史和肥胖情况获得的结果具有可比性。
这项大规模的全国性病例-时间-对照研究为GLP-1 RA的短期精神安全性提供了保证，表明对患有精神疾病或肥胖症的患者没有特定风险。
法国药品管理局。
