Real-World Data in Pharmacovigilance Database Provides a New Perspective for Understanding the Psychiatric Adverse Events Associated with Glucagon-Like Peptide-1 Receptor Agonists (Glp-1 RAs) Exposure

Abstract

The glucagon-like peptide-1 receptor agonists (GLP-1 RAs) were attractive options for the treatment of diabetes and obesity. Recently, the suicidal risk of GLP-1 RAs has aroused people’s attention. The aim of this study was to explore the psychiatric safety profiles of GLP-1 RAs using Food and Drug Administration Adverse Event Reporting System database. Disproportionality analysis was used to detect safety signals by calculating Reporting Odds Ratios. Preferred Terms (PTs) under 5 High-Level Group Terms categories that are of high concern to clinicians and patients, which might be associated with suicidality, were further investigated. Psychiatric adverse events accounted for 10.21% of all reported adverse drug events (ADEs) for GLP-1 RAs. The most frequent manifestations were nervousness, stress, anxiety, and depression. 16 positive signals at the PT level in psychiatric system were uncovered for exenatide, dulaglutide and semaglutide, namely listless, nervousness, frustration tolerance decreased, sleep disorder due to general medical condition (insomnia type), sleep disorder due to a general medical condition, fear of injection, fear of eating, eating disorder, binge eating, self-induced vomiting, aversion and intrusive thoughts. Disproportionate reporting of suicidal ideation and depression/suicidal was also observed with semaglutide. The incidence of psychiatric disorders reported in women is more than twice that of men. The occurrence of psychiatric disorder was common for individuals taking GLP-1 RAs. Clinicians should monitor for and advise patients using GLP-1 RAs to report new or worsening psychiatric symptoms, suicidal thought or any unusual changes in mood or behavior.

Note:
Funding declaration: This work was supported by a grant from the Chongqing Medical Scientific Research Project (Joint project of Chongqing Health Commission and Science and Technology Bureau) (2022MSXM049), the Natural Science Foundation of Chongqing, China (cstc2021jcyj-msxmX1089), and the Program for Youth Innovation in Future Medicine, Chongqing Medical University (W0208).

Conflict of Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Keywords: Glucagon-Like Peptide-1 Receptor Agonists, FDA Adverse Event Reporting System, Psychiatric Adverse Events, Suicidality, Reporting Odds Ratios