GLP ‐1 Receptor Agonists and Psychiatric Outcomes in Adolescents: A Systematic Review and Meta‐Analysis

ABSTRACT Aims To assess the association between GLP‐1 receptor agonists (GLP‐1 RAs) and psychiatric outcomes in adolescents. Materials and Methods We conducted a systematic review and meta‐analysis following PRISMA 2020 guidelines. We searched PubMed, EMBASE and the Cochrane Library. We included randomized controlled trials (RCTs) and observational cohort studies of adolescents that compared GLP‐1 RAs prescribed for overweight, obesity or type 2 diabetes with placebo, no treatment or standard of care. We assessed suicidal ideation, suicide attempts and depression. We pooled risk ratios with 95% confidence intervals (CIs). We assessed heterogeneity with I 2 and χ 2 and used sensitivity and subgroup analyses to test robustness of our data. We assessed risk of bias using RoB 2 (randomized trials) and ROBINS‐I (observational studies) tools. We graded the certainty of evidence using the GRADE framework. Results We included 11 studies (9 RCTs, n = 1253; 2 observational, n = 8922; total n = 10 175). GLP‐1 RAs were associated with a lower risk of suicidal ideation versus control (RR 0.73; 95% CI: 0.54–0.99; p = 0.046; I 2 = 0%). We found no significant effects versus control on suicide attempts (RR 0.66; 95% CI: 0.16–2.61; p = 0.444; I 2 = 0%) or depressive symptoms (RR 0.73; 95% CI: 0.36–1.48; p = 0.282; I 2 = 50.4%). Conclusions GLP‐1 RAs were not associated with higher rates of suicidal behaviour or depression in adolescents. Pooled analysis suggested a possible lower risk of suicidal ideation, although this finding should be interpreted cautiously.