Risk of Suicidal Ideation or Attempts in Adolescents With Obesity Treated With GLP1 Receptor Agonists

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.

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.