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

AI Summary

Evidence from 43 observational studies is mixed; no definitive causal link between GLP-1 RAs and suicidality, but some agents show signals.
Case reports suggested temporal links; cross sectional and case control studies found reduced suicide attempts, while cohort and pharmacovigilance results were inconsistent.
Clinicians should routinely assess mental health before and during treatment; mental health history is not an absolute contraindication to GLP-1 RA use.

Diabetes Obes Metab. 2026 May 18. doi: 10.1111/dom.70878. Online ahead of print.

ABSTRACT

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.

PMID:42150748 | DOI:10.1111/dom.70878

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