# Evaluating Suicidal Risk in GLP-1RA Therapy: An Umbrella Review of Meta-Analytic Evidence

## TL;DR

This study reviews existing research to assess if GLP-1RA therapy is linked to increased suicidal risk, finding no significant association.

## Contribution

This is the first umbrella review to synthesize evidence on GLP-1RAs and suicidality.

## Key findings

- Most studies found no significant association between GLP-1RAs and suicidality.
- Suicidality was linked to unrealistic treatment expectations, being underweight, and use of semaglutide and liraglutide.
- GLP-1RAs were associated with improvements in symptoms, quality of life, and diabetes distress.

## Abstract

Objective: This is the first umbrella review to integrate the available research syntheses on the associations between glucagon-like peptide-1 receptor agonists (GLP-1RAs) and suicidality. Methods: A systematic search within the main databases (MedLine, PubMed, PsychInfo, Web of Science, Science Direct, Sage, Wiley, Scopus, Google Scholar, Proquest, and Cochrane Library) was performed using the main key words. Out of a total of 50 initial studies, a final number of 12 reviews and meta-analyses were included in the study. Results: Except for two observational studies, the results consistently found no significant association between GLP-1RAs and suicidality, though improvements in symptomatology (as found in five studies), quality of life (three studies), and diabetes distress (one study) were highlighted. Although no causal effect could be yielded, an association was observed between suicidality and having unrealistic treatment expectations, being underweighted, and being treated with semaglutide and liraglutide (as indicated by two studies). Conclusion: GLP-1RA treatment represents a safe option when treating diabetes/obesity. However, a careful assessment of treatment expectations and of suicide risk is needed in order to attenuate potential suicidal tendencies that already exist.