ImportanceGlucagon-like peptide 1 receptor agonists (GLP1R) are increasingly being used for the treatment of obesity in adolescents. It is currently unknown whether GLP1R treatment is associated with suicidal ideation or attempts in this population.ObjectiveTo investigate the association between GLP1R initiation and suicidal ideation or attempts in adolescents with obesity.Design, Setting, and ParticipantsRetrospective propensity score–matched cohort study using electronic health records from the TriNetX global federated network between December 2019 and June 2024. The analysis included data from 120 health care organizations, mainly from the USA. Participants were adolescents aged 12 to 18 years with a diagnosis of obesity and evidence of an antiobesity GLP1R prescription or lifestyle intervention without GLP1R within the following year. Cohorts were balanced for baseline demographic characteristics, psychiatric medications and comorbidities, and diagnoses associated with socioeconomic status and health care access using propensity score matching.ExposureInitial prescription of GLP1R (study cohort) or lifestyle intervention without GLP1R (control cohort).Main Outcomes and MeasuresIncidence of suicidal ideation or attempts based on International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes recorded in patient electronic health records during 12 months of follow-up. Diagnoses of upper respiratory tract infections (URTI) were used as negative control outcomes, and gastrointestinal symptoms (GI) were used as positive control outcomes.ResultsA total of 4052 adolescents with obesity and a concomitant antiobesity intervention were identified for the GLP1R cohort and 50 112 were identified for the control cohort. Propensity score matching resulted in 3456 participants in each balanced cohort. Prescription of GLP1R was associated with a 33% reduced risk for suicidal ideation or attempts over 12 months of follow-up (1.45% vs 2.26%; hazard ratio [HR], 0.67; 95% CI, 0.47-0.95; P = .02) and a higher rate of GI symptoms (6.9% vs 5.4%; HR, 1.41; 95% CI, 1.12-1.78; P = .003) but no difference in rates of URTI diagnoses.Conclusions and RelevanceIn this study, adolescents with obesity prescribed a GLP1R had a lower incidence of suicidal ideation or attempts compared with matched patients not prescribed GLP1R who were treated with lifestyle intervention. These results suggest a favorable psychiatric safety profile of GLP1R in adolescents. The detected reduction in HRs for suicidal ideation among adolescents with obesity prescribed GLP1R suggests potential avenues for future research.

中文翻译：

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接受 GLP1 受体激动剂治疗的肥胖青少年有自杀意念或企图的风险


重要性胰高血糖素样肽 1 受体激动剂 （GLP1R） 越来越多地用于治疗青少年肥胖症。目前尚不清楚 GLP1R 治疗是否与该人群的自杀意念或企图有关。目的探讨肥胖青少年 GLP1R 启动与自杀意念或企图的相关性。设计、设置和参与者回顾性倾向评分匹配的队列研究使用 2019 年 12 月至 2024 年 6 月期间来自 TriNetX 全球联合网络的电子健康记录。该分析包括来自 120 个医疗保健组织的数据，主要来自美国。参与者是 12 至 18 岁的青少年，被诊断为肥胖，并有证据表明在接下来的一年内有抗肥胖 GLP1R 处方或没有 GLP1R 的生活方式干预。使用倾向评分匹配对基线人口统计学特征、精神科药物和合并症以及与社会经济地位和医疗保健可及性相关的诊断对队列进行平衡。暴露GLP1R 的初始处方（研究队列）或没有 GLP1R 的生活方式干预（对照组）。主要结局和措施在 12 个月的随访期间，基于疾病和相关健康问题国际统计分类第十次修订代码记录在患者电子健康记录中的自杀意念或企图的发生率。上呼吸道感染 （URTI） 的诊断用作阴性对照结局，胃肠道症状 （GI） 用作阳性对照结局。结果GLP1R 队列共确定了 4052 例肥胖青少年并同时进行了抗肥胖干预，对照组共确定了 50 112 例。 倾向得分匹配导致每个平衡队列中有 3456 名参与者。在 12 个月的随访中，GLP1R 处方与自杀意念或企图自杀风险降低 33% 相关 （1.45% vs 2.26%;风险比 [HR]，0.67;95% CI，0.47-0.95;P = .02） 和较高的胃肠道症状发生率 （6.9% 对 5.4%;心率，1.41;95% CI，1.12-1.78;P = .003），但 URTI 诊断率没有差异。结论和相关性在本研究中，与接受生活方式干预治疗的未开具 GLP1R 的匹配患者相比，开具 GLP1R 处方的肥胖青少年自杀意念或企图的发生率较低。这些结果表明 GLP1R 在青少年中具有良好的精神安全性。在服用 GLP1R 的肥胖青少年中检测到自杀意念的 HR 减少，这表明未来研究的潜在途径。