Association of Glucagon-Like Peptide-1 Receptor Agonists and Suicidality: A Systematic Review

Increased risk of suicidality has been reported in association with glucagon-like peptide receptor agonist (GLP-1 RA) prescription. Herein, we conducted a comprehensive review evaluating reports of GLP-1 RA prescription and suicidality.

Relevant articles were retrieved from OVID (Medline, EMBASE, AMED, PsycINFO, JBI EBP Database), PubMed, and Web of Science from inception to May 20, 2024. Primary research examining the association between GLP-1 RAs (i.e., dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide, tirzepatide) and suicidality were included for analysis.

Our findings indicate liraglutide (reported odds ratio [ROR] = 3.26, 95% CI = 2.53, 4.22) and semaglutide (ROR = 1.73; 95% CI = 0.30, 0.80) are significantly associated with a greater odds ratio of reported suicidal ideation. Similarly, tirzepatide was associated with greater odds of reported suicidal ideation; however, this was nonsignificant (ROR = 1.49; 95% CI = -0.41, 1.21). Similarly, semaglutide (ROR = 8.81; 95% CI = 3.69, 21.04) and liraglutide (ROR = 3.74; 95% CI = 1.23, 11.38) are also associated with a greater odds ratio of reported suicidal depression. No significant association between other GLP-1 RAs and suicidality was observed.

Reports of aspects of suicidality and exposure to select GLP-1 RAs exist; notwithstanding, no causality between GLP-1 RA exposure and suicidality is apparent.