Psychiatric adverse events associated with GLP-1 receptor agonists: a real-world pharmacovigilance study based on the FDA Adverse Event Reporting System database

Abstract

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used due to their profound efficacy in glycemic control and weight management. Within real-world contexts, the manifestation of certain psychiatric adverse events (AEs) has been observed, which is potentially linked to the administration of GLP-1 RAs. The objective of this study was to undertake a comprehensive investigation and characterization of the psychiatric AEs associated with GLP-1 RAs.

Methods: We retrieved reports of AEs associated with treatment with GLP-1 RAs during the period from the first quarter (Q1) of 2004 to Q1 2023 from the FDA Adverse Event Reporting System (FAERS) database. Descriptive analysis was performed to examine the clinical characteristics and time to onset of the psychiatric AEs caused by GLP-1 RAs. Moreover, disproportionality analyses were performed using the reporting odds ratio (ROR) to identify GLP-1 RA-related psychiatric AEs.

Results: A total of 8,240 reports of psychiatric AEs were analyzed out of 181,238 AE reports with treatment with GLP-1 RAs. Among these cases, a higher percentage was represented by women compared to men (65.89% vs. 30.96%). The median age of these patients was 56 years, with an interquartile range (IQR) of 48-67 years, based on data available in 286 case reports. This study showed that the median time to onset of the overall GLP-1 RA-related AEs was 31 days (IQR = 7-145.4 days), which varied among GLP-1 RA regimens. Specifically, exenatide had a significantly longer onset time at 45 days (IQR = 11-213 days), with statistically significant differences from the onset times of the other five GLP-1 RAs (p< 0.0001). Moreover, eight categories of psychiatric AEs, namely, nervousness (ROR = 1.97, 95% CI = 1.85-2.11), stress (ROR = 1.28, 95% CI = 1.19-1.38), eating disorder (ROR = 1.57, 95% CI = 1.40-1.77), fear of injection (ROR = 1.96, 95% CI = 1.60-2.40), sleep disorder due to general medical condition-insomnia type (ROR = 2.01, 95% CI = 1.60-2.52), binge eating (ROR = 2.70, 95% CI = 1.75-4.16), fear of eating (ROR 3.35, 95% CI = 1.65-6.78), and self-induced vomiting (ROR = 3.77, 95% CI = 1.77-8.03), were defined as GLP-1 RA-related psychiatric AEs through disproportionality analysis.

Conclusion: Our findings demonstrate a significant association between GLP-1 RAs and the development of specific psychiatric AEs. Despite the observational nature of this pharmacovigilance study and the inherent limitations of the FAERS database, our preliminary findings in this work could provide a better basis for understanding the potential psychiatric AEs that may occur with GLP-1 RA treatment, assisting clinicians to focus on these AEs and provide early intervention for optimal risk management.

Keywords: FAERS database; disproportionality analyses; glucagon-like peptide-1 receptor agonists; pharmacovigilance study; psychiatric adverse events.

Figure 1

Flow diagram of the screening of psychiatric adverse events (AEs) of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) from the FDA Adverse Event Reporting System (FAERS) database.

Figure 2

Cumulative distribution curves demonstrating the onset time of glucagon-like peptide-1 receptor agonist (GLP-1 RA)-related psychiatric adverse events (pAEs) after treatment with different GLP-1 RAs.

Figure 3

Scanning for glucagon-like peptide-1 receptor agonist (GLP-1 RA)-related psychiatric adverse events (AEs) based on the FDA Adverse Event Reporting System (FAERS) database. (A) Heatmap showing the reporting odds ratio (ROR) for the top 40 psychiatric AEs (with reports no less than 5) in the FAERS database under different GLP-1 RA treatment strategies (including overall, exenatide, liraglutide, lixisenatide, dulaglutide, semaglutide, and tirzepatide). Red indicates the lower limit of the 95% confidence interval for an ROR greater than 1, dark blue indicates the lower limit of the 95% confidence interval for an ROR less than 1, and light blue indicates ROR values that could not be calculated. (B) Bar plot showing the number of reported cases for eight categories of GLP-1 RA-related psychiatric AEs with different GLP-1 RA treatments. (C) Forest plot showing the ROR of GLP-1 RA-related psychiatric AEs with different GLP-1 RA treatments. NS, not significant. ****p< 0.0001.