Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and suicidality: A replication study using reports to the World Health Organization pharmacovigilance database (VigiBase®)
Bibliographic record
Abstract
INTRODUCTION: Reports of suicidality associated with glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have been reported to the European Medicines Agency (EMA) and the United States Food and Drug Administration (FDA). We previously reported an increased reporting odds ratio (ROR) of some measures of suicidality with semaglutide and liraglutide using the FDA Adverse Event Reporting System (FAERS). Notwithstanding the increased ROR, causality between GLP-1 RAs exposure and any aspect of suicidality is not established. RESEARCH DESIGN AND METHODS: The analysis herein aims to extend a previous analysis of the FAERS by evaluating the ROR for suicidality reported to the World Health Organization (WHO) Pharmacovigilance Database (VigiBase). We aimed to characterize the ROR of suicidality associated with GLP-1 RAs, as extrapolated from spontaneous reports. As per our previous report, the ROR was considered significant when the lower limit of the 95 % confidence (CI) was >1.0. RESULTS: We searched VigiBase reports from inception to January 2024. The RORs for suicidal ideation were significantly increased for semaglutide (5.82), liraglutide (4.03) and tirzepatide (2.25). For "depression/suicidal", the ROR was significantly increased for semaglutide (14.74) and liraglutide (5.86); and for suicidal behaviour, the ROR was significantly increased for semaglutide (6.52) and liraglutide (3.90). However, for suicide attempts, the ROR was significantly decreased for semaglutide (0.11), dulaglutide (0.075), exenatide (0.047) and liraglutide (0.15). For completed suicide, the ROR was also significantly decreased for semaglutide (0.01), dulaglutide (0.003), exenatide (0.002) and liraglutide (0.008). CONCLUSION: Unlike our previous report with FAERS, a mixed pattern of ROR emerged in the WHO VigiBase with respect to suicidality and exposure to select GLP-RAs. Causation between GLP-1 RA exposure and suicidality (either increased or decreased) cannot be ascertained from ROR data.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.002 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".