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

AIMS: We aimed to examine the association between GLP-1 RA use and suicidal ideation or behaviours through a systematic review of observational studies. MATERIALS AND METHODS: A comprehensive search of MEDLINE, PubMed, EMBASE, CINAHL and PsycINFO was conducted from database inception through December 11, 2025. Observational studies investigating suicidal ideation, suicide attempts or complete suicide among adults using GLP-1 RAs were included. Eligibility screening, data extraction and risk of bias assessments were performed independently and in duplicate, with disagreements resolved by a third reviewer. RESULTS: Forty-three studies were included. Findings varied by study design. Some case reports suggested a temporal relationship between GLP-1 RA use and suicidal ideation. Cross-sectional studies and case-control studies identified a negative association between GLP-1 RAs and suicide attempts. Pharmacovigilance and cohort studies showed more mixed results, with some studies identifying a positive association between semaglutide or liraglutide and suicidal ideation, while others paradoxically reported a negative association with suicidal behaviours (i.e., attempts and intentional self-harm) or completed suicide. CONCLUSIONS: While evidence does not support GLP-1 RAs as a causative agent for suicidality, due to multiple risk factors in this population, clinicians should routinely assess mental health status before and during GLP-1 RA treatment regardless of indication. Importantly, a history of concurrent mental health conditions should not preclude use of a GLP-1 RA; rather, individual patient factors should be accounted for when making prescribing decisions.