Assessing the shadows: A meta-analysis of GLP-1 agonists and suicidal ideation.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 agonist) have revolutionized the treatment of obesity. However, regulatory agencies have reported an association with suicidality. To the best of our knowledge, this is the first meta-analysis to assess the association between GLP-1 agonist use, suicidal ideation, and suicide completion. We aimed to assess the same in patients with diabetes and obesity. METHODS: We searched 6 databases for relevant articles, from the first published article to October 2024. The keywords used were GLP-1 agonists, suicidal ideation, suicide, suicidal behavior, semaglutide, liraglutide, tripeptide, exenatide, and lixisenatide. We identified 354 studies and 126 stands after the removal of duplicates, of which 23 were eligible, and only 12 studies were included in the final meta-analysis. RESULTS: No significant statistical difference was found in suicidal ideations in patients on GLP-1 agonists compared to their counterparts on other obesity and diabetes drugs (odds ratio [OR], 1.0; 95% confidence interval [CI]: 1.0-1.0). No significant difference was observed between patients on GLP-1 agonists and their counterparts regarding complete suicide (OR, 1.77; 95% CI: 0.80-3.91). In a subgroup analysis, suicide was higher among patients on liraglutide compared to their counterparts on semaglutide (OR, 1.48; 95% CI: 1.17-1.89). No significant statistical difference was observed when comparing monjaro and semaglutide (OR, 0.98; 95% CI: 0.94-1.03). CONCLUSION: No significant statistical difference was found between GLP-1 agonists and other obesity and diabetes drugs regarding suicide/suicidal ideation. In a subgroup analysis, suicide was higher in patients on liraglutide compared to semaglutide, with no significant difference between semaglutide and monjaro. Randomized controlled trials that assess the association between GLP-1 agonists and suicidality are highly recommended.