Analysis of the WHO global adverse event database found a statistically significant signal for semaglutide-associated suicidal ideation (ROR 1.45), but not for liraglutide, with the signal strengthening in patients co-taking antidepressants or benzodiazepines.
ROR 1.45 for suicidal ideationSemaglutide showed a 45% higher reporting rate for suicidal ideation compared to all other drugs in the WHO global adverse event database
What the researchers found
Significant disproportionality was detected for semaglutide-associated suicidal ideation (ROR 1.45, 95% CI 1.18-1.77). Signal strengthened in patients co-taking antidepressants (ROR 4.45) or benzodiazepines (ROR 4.07). Remained significant vs comparators: dapagliflozin (ROR 5.56), metformin (ROR 3.86), orlistat (ROR 4.24). No significant signal detected for liraglutide.
Why it matters
With tens of millions of people now taking semaglutide worldwide, even a small increased risk of suicidal ideation could affect thousands. This WHO database signal — while not proving causation — warrants urgent investigation given the scale of semaglutide prescribing.
The numbers in context
Analysis used the WHO global database. Published in JAMA Network Open.
How the study worked
Disproportionality analysis using a case-control design in the WHO global database (VigiBase) of suspected adverse drug reactions. Reporting odds ratios (ROR) and Bayesian information components (IC) calculated for semaglutide and liraglutide vs all other medications. Sensitivity analyses included patients co-taking antidepressants/benzodiazepines and comparisons with dapagliflozin, metformin, and orlistat.
Who was studied
Global adverse drug reaction reports in the WHO database
What this study cannot tell us
Disproportionality analysis cannot establish causation — only signal detection. WHO VigiBase has reporting bias (increased media attention may drive more semaglutide reports). No individual patient-level data to assess confounders. Many semaglutide users have obesity/diabetes, which are independently associated with depression. Signal was found for semaglutide but not liraglutide (both GLP-1 agonists), which is mechanistically puzzling.
How to read the evidence
Rated strong: published in JAMA Network Open using the WHO's comprehensive global pharmacovigilance database with robust statistical methodology and multiple sensitivity analyses. However, disproportionality analysis is hypothesis-generating, not hypothesis-confirming.
When this study was published
Published in 2024. Timely given the exponential growth in semaglutide prescriptions and ongoing regulatory review of suicidality risk.
The bigger picture
This study adds to a growing safety debate around GLP-1 peptide drugs. While the signal is modest and disproportionality analysis cannot prove causation, the finding that the signal is amplified in patients already taking psychiatric medications raises important questions about monitoring patients with pre-existing mental health conditions who start semaglutide.
Questions still open
- Is there a true causal link between semaglutide and suicidal ideation, or is this signal driven by reporting bias?
- Why does semaglutide show a signal but liraglutide does not, given they target the same receptor?
- Should patients with pre-existing depression or anxiety be monitored more closely when starting semaglutide?
Common questions
Does semaglutide cause suicidal thoughts?
Should I stop semaglutide if I have depression?
Read the original research
Disproportionality Analysis From World Health Organization Data on Semaglutide, Liraglutide, and Suicidality.
JAMA network open, 7(8), e2423385
Citation
Schoretsanitis, Georgios; Weiler, Stefan; Barbui, Corrado; Raschi, Emanuel; Gastaldon, Chiara. (2024). Disproportionality Analysis From World Health Organization Data on Semaglutide, Liraglutide, and Suicidality.. JAMA network open, 7(8), e2423385. https://doi.org/10.1001/jamanetworkopen.2024.23385