A recent retrospective cohort study investigated the association between glucagon-like peptide-1 receptor agonists and suicidal ideation or attempts in adolescents with obesity.
In the study, published in JAMA Pediatrics, investigators found that glucagon-like peptide-1 (GLP-1) receptor agonist initiation was associated with a 33% lower risk of suicidal ideation or attempts compared with lifestyle interventions alone.
The study included 6,912 adolescents aged 12 to 18 years, all diagnosed with obesity. The patients were drawn from the TriNetX global federated network, with data collected between December 2019 and June 2024. The participants were divided into two cohorts: one receiving antiobesity GLP-1 receptor agonists (liraglutide or semaglutide) and a control group receiving only lifestyle interventions. Propensity score matching was used to balance baseline demographics, psychiatric comorbidities, and other potential confounders. A total of 3,456 adolescents were matched in each cohort.
The primary outcome of interest was the incidence of suicidal ideation or attempts, determined using ICD-10 codes. Over a 12-month follow-up period, 1.45% of the patients in the GLP-1 receptor agonist cohort experienced suicidal ideation or attempts compared with 2.26% in the control cohort. The hazard ratio (HR) was 0.67 (95% confidence interval [CI] = 0.47–0.95, P = .02), indicating a significant reduction in risk.
The incidence of gastrointestinal symptoms was higher in the GLP-1 receptor agonist cohort compared with the control cohort (6.9% vs 5.4%, HR = 1.41, 95% CI = 1.12–1.78, P = .003). No statistically significant differences were observed in the incidence of upper respiratory tract infections, which served as a negative control outcome (10.33% vs 10.88%, HR = 1.01, 95% CI = 0.88–1.17, P = .88). Additionally, the incidence of acute pancreatitis was lower in the GLP-1 receptor agonist cohort compared with the control cohort (0.29% vs 0.67%, HR = 0.41, 95% CI = 0.19–0.88, P = .02).
Sensitivity analyses were conducted to assess the robustness of the findings. Subgroup analyses were performed based on sex, race and ethnicity, type of GLP-1 receptor agonist (liraglutide or semaglutide), diabetes status, and patients without prior bariatric surgery. The reduced risk of suicidal ideation or attempts remained consistent across these subgroups. An additional analysis starting 1 year prior to GLP-1 receptor agonist initiation found no statistically significant differences in baseline rates of suicidal ideation or attempts between the cohorts (1.52% vs 1.64%, HR = 0.93, 95% CI = 0.55–1.57, P = .79), supporting that the observed reduction was likely related to GLP-1 receptor agonist treatment.
Patients in the GLP-1 receptor agonist cohort were also more likely to receive additional antiobesity treatments during the follow-up period, with 68% of these patients having at least one additional prescription of a GLP-1 receptor agonist. The prescription of phentermine was more common in the GLP-1 receptor agonist cohort (4.32% vs 1.78%), whereas bariatric surgery was more common in the control cohort (2% vs 2.9%).
The investigators found that adolescents with obesity who were prescribed GLP-1 receptor agonists had a lower risk of receiving a diagnosis of suicidal ideation or attempt over 12 months of follow-up as well as up to 3 years in sensitivity analyses. This association was observed consistently across different patient demographics and GLP-1 receptor aognist types. Gastrointestinal symptoms, a known adverse effect of GLP-1 receptor agonists, were more prevalent in the treatment group, whereas the negative control outcomes showed no statistically significant differences between groups.
Although the observational nature of the study precluded definitive causal conclusions, these results suggested an association between GLP-1 receptor agonist treatment and reduced incidence of suicidal ideation in adolescents with obesity. Further research could help illuminate the underlying mechanisms and evaluate these findings in prospective clinical trials.
Conflict of interest disclosures can be found in the study.