Investigation of potential relationship between glucagon-like peptide 1 receptor agonists with suicide/self-injury: disproportionality analysis using WHO-VigiBase

Purpose: As global interest in glucagon-like peptide-1 receptor agonists (GLP-1 RAs) has increased owing to weight loss effect, concerns regarding the risk of suicide/self-injury associated with GLP-1 RAs have garnered considerable attention. Given the limited evidence, in this study, we aimed to investigate the potential relationship between GLP-1 RAs and suicide/self-injury, stratified by therapeutic indications, using VigiBase, the largest global database.Methods: Disproportionality analysis was conducted to detect signals of disproportionate reporting using VigiBase data from April 28, 2005, to August 31, 2023. Subgroup analyses by indication were conducted, comparing against drugs that have different mechanisms but are used for similar indications (type 2 diabetes mellitus [T2DM] treatment: glucose-lowering agents; weight loss: orlistat). Reporting odds ratio (ROR) and information component (IC) were used as signal detection indicators.Results: A total of 485 reports of suicide/self-injury associated with GLP-1 RAs were identified. Indication-integrated analyses did not indicate a potential relationship between any GLP-1 RA and suicide/self-injury. In subgroup analyses by indication, signals of disproportionate reporting were not detected in patients using GLP-1 RAs for T2DM treatment but were detected in patients using GLP-1 RAs for weight loss: total (ROR, 2.01; 95% confidence interval [CI], 1.34 to 3.01; IC025, 0.01), liraglutide (ROR, 2.26; 95% CI, 1.47 to 3.49; IC025, 0.14), semaglutide (ROR, 2.33; 95% CI, 1.31 to 4.14; IC025, 0.22).Conclusion: Given the differences in results by indication, this study highlights the need for post-marketing surveillance of the suicide/self-injury risk in non-T2DM populations using GLP-1 RAs for simple weight loss.