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.

Di Stefano R, Rindi LV, Baldini V, Rossi R, Pacitti F, Jannini EA, Rossi A

Diabetes & metabolic syndrome1 Apr 2025Cited by 16 (Europe PMC)

PMID40388845DOI10.1016/j.dsx.2025.103238PepBankPUB-40388845

Publisher page PubMedAsk about this study

Summary

AimsSuicide 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.MethodsThis 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.ResultsThe 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.ConclusionsAlthough 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.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study3

No result from this study comes from a test of the peptide.

Studies that did not test the peptide alone3

In this study, Tirzepatide was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Tirzepatide.

01HumanNot a test of Tirzepatide aloneSystematic reviewSafety outcome
In this systematic review of 16 studies, pooled GLP-1 receptor agonists and tirzepatide showed no consistent evidence of increased suicide risk among GLP-1 RA users.
In plain wordsA review of 16 studies of GLP-1 drugs and tirzepatide found no consistent sign of higher suicide risk in GLP-1 drug users.
Peptide
Tirzepatide
Outcome
No significant changeSuicidal ideation or behavior risk in GLP-1 RA users
Study
n: not reported in source
Outcome group
Adverse events · Mental health and mood
Source sentences
Summary
No consistent evidence indicated an increased suicide risk among GLP-1 RA users.
1 context sentence(design, population, supporting numbers)
Summary · context
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.
In this study, Tirzepatide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Tirzepatide.
Show in the study text Report a problemFND-4038884501
02HumanNot a test of Tirzepatide aloneSystematic reviewSafety outcome
In pharmacovigilance analyses of GLP-1 receptor agonists and tirzepatide, findings were mixed: some reported higher rates than other antihyperglycemic drugs, with no confirmed causal link.
In plain wordsDrug-safety report analyses of GLP-1 drugs and tirzepatide gave mixed results, and no causal link to suicidal behavior was confirmed.
Peptide
Tirzepatide
Outcome
MixedSuicidal behavior reports in pharmacovigilance analyses
Study
n: not reported in source
Outcome group
Adverse events · Mental health and mood
Source sentences
Summary
Pharmacovigilance analyses produced mixed findings; while some disproportionality analyses reported higher rates relative to other antihyperglycemic drugs, no causal link was confirmed.
1 context sentence(design, population, supporting numbers)
Summary · context
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.
In this study, Tirzepatide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Tirzepatide.
Show in the study text Report a problemFND-4038884502
03HumanNot a test of Tirzepatide aloneSystematic reviewSafety outcome
In cohort studies of people with diabetes or obesity, GLP-1 receptor agonists and tirzepatide generally did not show a significant increase in suicidal behavior.
In plain wordsIn cohort studies of people with diabetes or obesity, GLP-1 drugs and tirzepatide generally did not show higher suicidal behavior.
Peptide
Tirzepatide
Outcome
No significant changeSuicidal behavior in cohort studies
Study
n: not reported in source
Outcome group
Adverse events · Mental health and mood
Source sentences
Summary
Cohort studies involving diabetic and obese populations generally did not demonstrate a significant increase in suicidal behavior.
1 context sentence(design, population, supporting numbers)
Summary · context
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.
In this study, Tirzepatide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Tirzepatide.
Show in the study text Report a problemFND-4038884503

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
12 Oct 2026, 12:58 UTC
Study results updated
Version 1
9 Oct 2026, 03:07 UTC
First added · source update from Europe PMC

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