Risk of Suicidal Ideation and Behaviors, Depression, and Anxiety with GLP-1 Receptor Agonist Use in Children and Adolescents: A Target Trial Emulation Study
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Importance
Rising rates of obesity and youth-onset type 2 diabetes (YT2D) in children and adolescents have increased GLP-1 receptor agonist (GLP-1 RA) use, raising concerns about potential effects on suicidal ideation/behaviors (SI/SB), depression, and anxiety.
Objective
To assess associations between GLP-1 RA use for obesity or YT2D and risk of SI/SB, depression, and anxiety in children and adolescents.
Setting
OneFlorida+ EHR from January 1, 2020, to January 31, 2024.
Design
Retrospective cohort study using prevalent-new user design, target trial emulation framework, and sIPTW for confounding control.
Participants
Children and adolescents with obesity or YT2D who were ≥6 and <18 years were included with no history of the respective outcomes.
Exposure
New GLP-1 RA users vs. Prevalent metformin users.
Outcomes
SI/SB, anxiety, and depression. Weighted Cox proportional hazards models were used to assess the risk of outcomes. Risk differences (RD) and hazard ratios (HR) are presented with 95% CI. RDs are per 1,000 person-years.
Results
The study included 2,010, 1,774, and 1,764 patients for SI/SB, depression, and anxiety, respectively. The mean age was ∼14.2 years, ∼61% were female, with up to 4 years of follow-up, across cohorts. Compared to prevalent metformin users, GLP-1 RA users had lower incidence and risk of SI/SB (RD: -10.45, -14.54 to -6.36; HR: 0.11, 0.02 to 0.86) and depression (RD: -25.64, -34.90 to -16.39; HR: 0.37, 0.17 to 0.78). There was no difference in anxiety risk between the two groups (RD: 5.95, -7.10 to 19.01; HR: 1.13, 0.69 to 1.84).
Conclusions
GLP-1 RA use may reduce the risks of SI/SB and depression among children and adolescents with obesity or YT2D; no association was found with anxiety. Long-term surveillance is needed.
KEY POINTS
Question
Are GLP-1 receptor agonists (GLP-1 RAs) for the indication of obesity or youth-onset type 2 diabetes (YT2D) associated with the risk of mental health outcomes in children and adolescents?
Findings
In this retrospective cohort study, including 2,116 children and adolescents with obesity or T2D, GLP-1 RA use was associated with a significantly lower risk of suicidal ideation and behaviors and depression when compared to prevalent metformin users. There was no significant difference in the risk of anxiety between the two groups.
Meaning
The results of this study suggest that children and adolescents using GLP-1 RA for obesity or YT2D were at lower risk of suicidal ideation and behaviors, and depression compared to prevalent metformin users. The risk of anxiety remained non-significant, but the higher trend warrants future surveillance by pediatricians, psychologists, and pharmacoepidemiologists.
