Risk of Suicidal Ideation and Behaviors, Depression, and Anxiety with GLP-1 Receptor Agonist Use in Children and Adolescents: A Target Trial Emulation Study
Abstract
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…
How strong is the evidence?
Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 2,116 participants or records.
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