Postmarket safety profile of suicide/self-injury for GLP-1 receptor agonist: a real-world pharmacovigilance analysis

Abstract

Background Recent reports of individuals experiencing suicidal and/or self-injurious behaviors while using liraglutide and semaglutide have heightened the concerns regarding neuropsychiatric safety of Glucagon-like peptide-1 agonists (GLP-1RAs). As real-world evidence is very limited, we explored the association between GLP-1RA and suicide/self-injury by mining the FDA Adverse Event Reporting System (FAERS) database. Methods The FAERS database was queried from 2005 Q2 to 2023 Q2. The Reporting Odds Ratio (ROR) and Empirical Bayes Geometric Mean (EBGM) were used to conduct the disproportionality analysis. Results A total of 534 GLP-1RA-associated suicide/self-injury cases were reported in the FAERS during the study period. GLP-1RA did not cause a disproportionate increase in overall suicidal and self-injurious cases (ROR: 0.16, 95%CI 0.15-0.18, P < 0.001; EBGM05: 0.15). Stratified analyses found no safety signal of suicide/injury for GLP-1RA in both females and males. The ROR for suicide/self-injury with GLP-1RA was slightly elevated (ROR: 2.50, 95%CI 1.02-6.13, P = 0.05) in children, while the EBGM05 was < 2 in this population. No significant signal value was observed in other age groups. No over-reporting of suicide/self-injury was identified for GLP-1RA before or after the COVID-19 pandemic outbreak. Conclusions The cases of suicide or self-injury reported to FAERS do not indicate any overall safety signal attributable to GLP-1RA at this time. Subgroup analysis revealed a marginal elevation of ROR for suicide and self-injury with GLP-1RA in children, but no safety signal was detected by EBGM05 in this population. Further large-scale prospective investigations are still warranted to further confirm this finding.

Exploration of the potential association between GLP-1 receptor agonists and suicidal or self-injurious behaviors: a pharmacovigilance study based on the FDA Adverse Event Reporting System database

“…The majority of SSIB cases reported in the current RCT and post-marketing study are not considered to be related to GLP-1 RAs. The disproportionate analyses conducted concurrently with our study, based on the FAERS database with varying year spans, also indicate no direct association between GLP-1RAs and SSIBs [ 55 , 56 ]. In a retrospective analysis utilizing electronic health records, researchers noted that semaglutide can even reduce the risk of suicide compared to non-GLP-1 RAs anti-obesity medications [ 57 ].…”

Glucagon-like Peptide-1 Receptor Agonists and Suicidal Ideation: Analysis of Real-Word Data Collected in the European Pharmacovigilance Database

“…The evidence evaluating this risk is meagre. Few recent studies have questioned this association [ 9 , 10 , 11 ], and no study has compared this risk between different GLP-1 RAs. Clinical trials have several limitations related to their duration and patient inclusion criteria that can impede investigations on psychiatric adverse events.…”

Pharmacovigilance study of GLP-1 receptor agonists for metabolic and nutritional adverse events

“…Some concerns have been raised among healthcare professionals over the safety profiles of GLP-1 Ras. There have been reports of suicidal or self-injurious behaviors (SSIBs) to the European Medicines Agency (EMA), although pharmacovigilance reviews have reported no direct link between GLP-1 RAs and SSIBs ( Chen et al, 2023 ; Chen et al, 2024 ; Zhou et al, 2024 ). Increased risks of thyroid cancer and cholecystitis have been reported ( He et al, 2022 ; Bezin et al, 2023 ).…”