Analysis of Spontaneous Reports of Psychiatric Adverse Events Associated with GLP-1 Analogues

Glucagon-like peptide 1 (GLP-1) analogues constitute a group of drugs that promote insulin secretion in a glucose-dependent manner and reduce the speed of gastric emptying. As prescriptions for these agents grow rapidly, the possibility of psychiatric side effects has not been thoroughly examined. The objective of this pharmacovigilance analysis was to assess the frequency of psychiatric adverse events (AEs) related to all marketed GLP-1 analogues using open-access national reporting systems from the United States (FAERS), Canada (CVAROD), and Australia (DAEN). All reports involving psychiatric AEs for approved GLP-1 analogues were collected from the three databases. Disproportionality measures were calculated, including reporting odds ratios (RORs) with corresponding 95% confidence intervals (CIs), for specific psychiatric events of concern.  Strong signals were detected when increased RORs appeared in more than one database. Semaglutide displayed connections to 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 demonstrated a link to depression (CVAROD, ROR = 1.68 CI 1.12–2.51), and dulaglutide exhibited signals for eating disorders (FAERS, ROR = 1.47 CI 1.26–1.71) as well as insomnia (FAERS, ROR = 2.93 CI 2.35–3.66).  Certain GLP-1 analogues, notably semaglutide and liraglutide, show notable links to psychiatric adverse events, including depression and thoughts of suicide. More research is essential to clarify the underlying processes, especially among those with prior mental health issues.