Kerem Liya, Stokar Joshua
Division of Pediatric Endocrinology, Department of Pediatrics, Hadassah University Medical Center, Jerusalem, Israel.
Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
JAMA Pediatr. 2024 Dec 1;178(12):1307-1315. doi: 10.1001/jamapediatrics.2024.3812.
Glucagon-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.
To investigate the association between GLP1R initiation and suicidal ideation or attempts in adolescents with obesity.
DESIGN, SETTING, AND PARTICIPANTS: Retrospective 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.
Initial prescription of GLP1R (study cohort) or lifestyle intervention without GLP1R (control cohort).
Incidence 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.
A 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.
In 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.
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自杀企图有关。
研究GLP1R起始治疗与肥胖青少年自杀意念或自杀企图之间的关联。
设计、设置和参与者：回顾性倾向评分匹配队列研究，使用2019年12月至2024年6月期间TriNetX全球联合网络的电子健康记录。分析包括来自120个医疗机构的数据，主要来自美国。参与者为12至18岁的青少年，诊断为肥胖症，并有抗肥胖GLP1R处方或下一年无GLP1R的生活方式干预的证据。使用倾向评分匹配使队列在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方面达到平衡。
GLP1R的初始处方（研究队列）或无GLP1R的生活方式干预（对照队列）。
基于国际疾病和相关健康问题统计分类第十次修订版代码，在12个月随访期间患者电子健康记录中记录的自杀意念或自杀企图的发生率。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。
共确定了4052名肥胖且同时进行抗肥胖干预的青少年纳入GLP1R队列，50112名纳入对照队列。倾向评分匹配后，每个平衡队列中有3456名参与者。GLP1R处方与随访12个月内自杀意念或自杀企图风险降低33%相关（1.45%对2.26%；风险比[HR]，0.67；95%置信区间，0.47 - 0.95；P = 0.02），且胃肠道症状发生率更高（6.9%对5.4%；HR，1.41；95%置信区间，1.12 - 1.78；P = 0.003），但URTI诊断率无差异。
在本研究中，与接受生活方式干预且未开具GLP1R处方的匹配患者相比，开具GLP1R处方的肥胖青少年自杀意念或自杀企图的发生率较低。这些结果表明GLP1R在青少年中具有良好的精神安全性。在开具GLP1R处方的肥胖青少年中检测到的自杀意念风险比降低提示了未来研究的潜在途径。
