Glucagon-Like Peptide-1 receptor agonists, dual GIP/GLP-1 receptor agonist tirzepatide and suicidal ideation and behavior: A systematic review of clinical studies and pharmacovigilance reports
Bibliographic record
Abstract
Suicide is a global public health concern, accounting for nearly 700,000 deaths annually. Although well-established risk factors, including mental health disorders, are widely recognized, emerging concerns have surfaced regarding a potential association between glucagon-like peptide-1 receptor agonists (GLP-1 RAs), the dual Gastric Inhibitory Polypeptide (GIP)/GLP-1 Receptor Agonist tirzepatide and suicidal behavior. This systematic review aims to synthesize the available evidence on the potential association between these drugs and suicidal behavior. This review was conducted following PRISMA guidelines. A systematic search was performed in MEDLINE, Embase, and APA PsycInfo up to September 24, 2024, using terms related to GLP-1 RAs/GIP/GLP-1 RAs and suicidal behavior.Three independent reviewers conducted article screening and data extraction. Risk of bias was evaluated using the Newcastle-Ottawa Scale for cohort studies and ROB2 for RCTs. The review identified 16 studies published between 2017 and 2024, consisting of 5 observational studies, 2 randomized controlled trials, 8 pharmacovigilance analyses, and 1 post-hoc analysis of RCTs. No consistent evidence indicated an increased suicide risk among GLP-1 RA users. Pharmacovigilance analyses produced mixed findings; while some disproportionality analyses reported higher rates relative to other antihyperglycemic drugs, no causal link was confirmed. Cohort studies involving diabetic and obese populations generally did not demonstrate a significant increase in suicidal behavior. Although current data do not warrant changes in prescribing practices, further research is needed before definitive conclusions can be drawn. Moreover, the generalizability and reliability of these findings should be interpreted in light of the methodological limitations of the included studies. • What is known about this research topic? - GLP-1 RAs and GIP/GLP-1 RAs are used for T2D and obesity and support better blood sugar, weight, and cardiovascular health. - Reports of psychiatric issues, including suicidal thoughts, during use have prompted investigations by health authorities. • What this study adds and its future implications - No consistent link found between these drugs and suicidal ideation and behavior in T2D or obesity treatment. - Risk of suicidal ideation with these drugs may be influenced by underlying mental health conditions. - More targeted research is needed to evaluate the psychiatric side effects of GLP-1 RAs/dual GIP/GLP-1 RAs.
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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 | 0.042 | 0.043 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.023 | 0.002 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.002 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| 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; both teacher heads agree on what is shown here.
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".