Association of Glucagon-Like Peptide-1 Receptor Agonists and Suicidality: A Systematic Review.
While some GLP-1 RAs show a significant association with suicidality, causality is not established, and clinical relevance is unclear.
Where it sits
this study against the rest of the lixisenatide corpusSummary and findings
This systematic review evaluated the association between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and suicidality. It found significant associations for liraglutide and semaglutide with increased odds of reported suicidal ideation and depression. No significant association was found for other GLP-1 RAs, including lixisenatide.
Abstract
<h4>Introduction</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Discussion</h4>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.
Background
The study addresses the concern of increased suicidality risk associated with GLP-1 RA prescriptions. Previous reports have suggested a potential link, but evidence has been inconsistent. This systematic review aims to provide a comprehensive evaluation of existing studies to clarify the association.
Methods
The review included primary research articles from databases such as OVID, PubMed, and Web of Science, covering studies from inception to May 20, 2024. It focused on the association between various GLP-1 RAs, including lixisenatide, and suicidality. The primary outcome was the reported odds ratio of suicidal ideation and depression.
Results
Liraglutide showed a significant association with increased odds of suicidal ideation (ROR = 3.26, 95% CI = 2.53, 4.22) and suicidal depression (ROR = 3.74, 95% CI = 1.23, 11.38). Semaglutide was also significantly associated with suicidal ideation (ROR = 1.73, 95% CI = 0.30, 0.80) and suicidal depression (ROR = 8.81, 95% CI = 3.69, 21.04). Tirzepatide's association with suicidal ideation was nonsignificant. No significant associations were found for other GLP-1 RAs, including lixisenatide.
Interpretation
The findings suggest a statistically significant association between certain GLP-1 RAs and suicidality, particularly for liraglutide and semaglutide. However, the clinical significance of these findings remains uncertain, as the review does not establish causality. The results should be interpreted with caution due to potential confounding factors and the reliance on reported odds ratios.
Key findings
- Liraglutide ROR = 3.26, 95% CI = 2.53, 4.22 for suicidal ideation.
- Semaglutide ROR = 1.73, 95% CI = 0.30, 0.80 for suicidal ideation.
- Tirzepatide ROR = 1.49, 95% CI = -0.41, 1.21 for suicidal ideation (nonsignificant).
- Semaglutide ROR = 8.81, 95% CI = 3.69, 21.04 for suicidal depression.
- Liraglutide ROR = 3.74, 95% CI = 1.23, 11.38 for suicidal depression.
Limitations
- No causality established.
- Reliance on reported odds ratios.
- Potential confounding factors.
- No significant findings for lixisenatide.