Association of GLP-1 Receptor Agonists With Risk of Suicidal Ideation and Behaviour: A Systematic Review and Meta-Analysis

Abstract

Background and Objective

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used to treat type 2 diabetes and obesity, providing metabolic and cardiovascular benefits. However, concerns have emerged about potential neuropsychiatric side effects, including suicidal ideation and behaviour, prompting investigations by regulatory bodies such as the FDA and EMA. This systematic review and meta-analysis aimed to assess the association between GLP-1RA use and the risk of suicidal ideation or behaviour.

Methods

A systematic literature search was conducted in PubMed, Embase, and Web of Science through September 2024, adhering to PRISMA guidelines. Observational cohort and case-control studies reporting suicidal ideation or behaviour in adults using GLP-1RAs were included. The Modified Newcastle-Ottawa Scale assessed risk of bias, and random-effect models calculated risk ratios (RR) with 95% confidence intervals (CIs). Heterogeneity was assessed using the I² statistic.

Results

Of 126 studies, 11 were included from multiple countries with diverse designs. The meta-analysis of four studies showed no statistically significant difference in suicidal outcomes between GLP-1RA users and users of other anti-hyperglycaemic drugs (RR: 0.568, 95% CI: 0.077–4.205). Substantial heterogeneity was observed (I² = 98%). Pharmacovigilance studies indicated no disproportionate increase in suicidality, while some observational studies suggested a lower risk.

Conclusion

This review found no significant link between GLP-1RA use and increased suicidal ideation or behaviour. However, the high heterogeneity and reliance on pharmacovigilance data suggest caution. Clinicians should monitor patients, particularly those with psychiatric conditions, and further research is needed to assess long-term neuropsychiatric safety.