The effect of glucagon-like Peptide-1 receptor agonists on measures of suicidality: A systematic review

Reports submitted to the FDA and EMA suggest that Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RAs) may be associated with an elevated risk of suicidality. To ascertain this association across available pharmacovigilance and cohort studies, Pubmed, Medline, Cochrane Library, PsychInfo, Embase, Scopus, and Web of Science were searched from database inception to November 20, 2024 in accordance with PRISMA guidelines. A manual search using Google Scholar was also conducted to identify additional studies. Cohort studies were assessed for quality using the Newcastle-Ottawa Scale. We endeavored to define and operationalize suicidality as suicide ideation (SI), suicide attempts (SA), and suicide completion (SC), in cases where study authors failed to separate these three dimensions, the term "suicidality" was applied. 22 studies meeting inclusion criteria comprised of pharmacovigilance (n = 10) and cohort studies (n = 12) were identified. Pharmacovigilance studies indicate that semaglutide and liraglutide are associated with disproportionate reporting of SI. Results from cohort studies indicate that GLP-1 RAs are not consistently associated with an increase in any aspect of suicidality; instead, some agents are associated with decreased SI and SA. There is inadequate information to ascertain whether causality exists linking GLP-1 RAs to suicidality. Ongoing vigilance and further information is required to inform if the possibility of causality exists. Practitioners prescribing GLP-1 RAs should be vigilant for the possibility of the emergence of SI and be aware of the higher risk of mental illness in persons who would be candidates for GLP-1 RAs (e.g. Type 2 Diabetes, obesity).