Assessing the shadows: A meta-analysis of GLP-1 agonists and suicidal ideation.
Alansari. Amal Omar AO; Alharbi. Ahlam Saleem AS; Alshehri. Khaled Mohammad KM; Alhabib. Ali Tareq AT; Alsalmi. Bodour Saleh BS; Almosfer. Waleed Abdulaziz WA; AlAjlan. Fadiyah Abdullah FA; Alharbi. Abeer Abdullah AA; Alzahrani. Basmah Saleh BS; Alamer. Bader B; Alatawi. Amirah M AM
Key Findings
- Overall GLPâ1 agonists did not increase suicidal thoughts or completed suicide (ORâ1.0).
- Liraglutide showed a higher suicide risk compared to semaglutide (ORâŻ1.48, 95%âŻCIâŻ1.17â1.89).
- No difference in suicide risk between semaglutide and the newer drug tirzepatide (Monjaro) (ORâŻ0.98).
Practical Outcomes
- If youâre using or considering semaglutide for weight loss or diabetes, the data suggest it doesnât add suicide risk, so you can continue without extra mentalâhealth monitoring beyond usual care. If you prefer liraglutide, be aware of a potential modest increase in suicide risk and watch for mood changes. Overall, keep an eye on emerging trials, but no protocol changes are needed right now.
Summary
A big review looked at whether weightâloss drugs that act like GLPâ1 (including semaglutide) increase thoughts of suicide or actual suicide. Overall, the drugs didnât raise the risk compared to other diabetes or obesity medicines, but one drug, liraglutide, showed a higher suicide rate than semaglutide. The evidence isnât strong enough to change anything dramatically, but it suggests semaglutide is not linked to higher suicidality, while liraglutide might need extra caution.
Abstract
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. 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. 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). 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.
Study Information
pubmed
2025
2025-12-05T00:00:00.000Z
10.1097/md.0000000000046173