Psychiatric adverse events linked to glucagon-like peptide 1 analogues: a disproportionality analysis in American, Canadian and Australian adverse event databases

Abstract

Background: Glucagon-like peptide 1 (GLP-1) analogues are a class of medications that stimulate glucose-dependent insulin release and slow gastric emptying. With the increasing use of GLP-1 analogues, concerns about potential psychiatric adverse events (AEs) remain under-explored.

Aim: This pharmacovigilance study aimed to investigate the prevalence of psychiatric AEs associated with currently available GLP-1 analogues by analysing publicly available national datasets from the US (FAERS), Canada (CVAROD) and Australia (DAEN).

Method: Psychiatric AE reports were extracted from all three databases for all approved GLP-1 analogues. A disproportionality analysis was conducted to calculate reporting odds ratios (RORs) and 95% confidence intervals (CIs) for psychiatric AEs of interest.

Results: Significant associations were identified when multiple databases reported elevated RORs. Semaglutide was associated with depressive symptoms (FAERS, ROR = 6.24 CI 4.49-8.69), panic attacks (FAERS, ROR = 1.46 CI 1.16-1.82) and suicidal ideation (FAERS, ROR = 2.58 CI 2.31-2.88). Liraglutide was linked to depression (CVAROD, ROR = 1.68 CI 1.12-2.51), while dulaglutide showed positive associations with eating disorders (FAERS, ROR = 1.47 CI 1.26-1.71) and insomnia (FAERS, ROR = 2.93 CI 2.35-3.66).

Conclusion: GLP-1 analogues, particularly semaglutide and liraglutide, are associated with significant psychiatric AEs, especially depression and suicidal ideation. Further studies are required to understand the mechanisms underlying these associations, particularly in patients with pre-existing psychiatric conditions.

Keywords: CVAROD; DAEN; FAERS; GLP-1 analogues; Pharmacovigilance; Psychiatric adverse events.