Comparative pharmacovigilance analysis of suicidality-related adverse events among GLP-1 and non-GLP-1 anti-obesity drugs in the FDA Adverse Event Reporting System.

INTRODUCTION: Regulatory reviews in 2023-2024 reignited concern about possible suicidality with Glucagon-like peptide-1 (GLP-1) receptor agonists used for weight management. While clinical trials and real-world studies have not confirmed an increased risk, comparative post-marketing analyses across all anti-obesity agents are scarce. AIM: To compare disproportional reporting of suicidality-related adverse events among GLP-1/dual incretin versus non-GLP-1 anti-obesity drugs in the FDA Adverse Event Reporting System (FAERS). METHOD: We conducted a retrospective disproportionality study using FAERS (January 2012-February 2025). Reports submitted from the United States with the study drug listed as primary suspect were retrieved via openFDA. Suicidality terms were predefined (MedDRA Preferred Terms: suicidal ideation, suicide attempt, completed suicide). Reporting Odds Ratios (RORs) with 95% confidence intervals (CIs) were calculated for each drug and at class level (GLP-1/dual incretin vs non-GLP-1). Haldane-Anscombe corrections were applied where needed. RESULTS: Among approximately 78,000 anti-obesity reports, 207 (approximately 0.3%) involved suicidality-related events. For semaglutide, RORs were 1.39 (95% CI 0.99-1.94) for suicidal ideation, 1.38 (0.46-4.15) for suicide attempt, and 1.72 (0.62-4.74) for completed suicide, none statistically significant. Liraglutide showed ROR 1.01 (0.66-1.55) for suicidal ideation and 18.11 (6.96-47.15) for completed suicide based on 14 cases. Tirzepatide yielded RORs below unity for all outcomes. Naltrexone/bupropion showed elevated disproportional reporting for suicidal ideation (ROR 3.84; 95% CI 2.89-5.12) and suicide attempt (ROR 4.11; 95% CI 1.62-10.45. CONCLUSION: GLP-1 and dual-incretin agents did not show disproportionality signals for suicidal ideation or suicide attempt. A statistically significant disproportionality signal for completed suicide was observed for liraglutide; however, this estimate was based on few cases and displayed wide confidence intervals, warranting cautious interpretation. These findings support an overall neutral psychiatric safety profile for incretin-based therapies while underscoring the need for continued monitoring of rare events such as completed suicide.