Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and suicidality: A replication study using reports to the World Health Organization pharmacovigilance database (VigiBase®).

McIntyre RS, Mansur RB, Rosenblat JD, Rhee TG, Cao B, Teopiz KM, Wong S, Le GH, Ho R, Kwan ATH

Journal of affective disorders19 Oct 2024Cited by 54 (Europe PMC)

PMID39433133DOI10.1016/j.jad.2024.10.062PepBankPUB-39433133

Publisher page PubMedAsk about this study

Summary

IntroductionReports 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 methodsThe 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.ResultsWe 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).ConclusionUnlike 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.

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

Results from this study13

13 results from studies that gave the peptide. 13 results from people.

01HumanObservational studySafety outcome
In VigiBase reports, semaglutide was linked to increased suicidal ideation reporting odds.
In plain wordsIn VigiBase reports, semaglutide was linked to increased reporting odds for suicidal thoughts.
Peptide
Semaglutide
Outcome
IncreaseSuicidal ideation reporting
Study
n: not reported in source
Outcome group
Adverse events · Mental health and mood
Studied dose
Dose not stated
Measurements
ROR
5.82 ratio
suicidal ideation
Source sentences
Summary
The RORs for suicidal ideation were significantly increased for semaglutide (5.82), liraglutide (4.03) and tirzepatide (2.25).
2 context sentences(design, population, supporting numbers)
Summary · context
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).
Summary · context
We aimed to characterize the ROR of suicidality associated with GLP-1 RAs, as extrapolated from spontaneous reports.
Show in the study text Report a problemFND-3943313301
02HumanObservational studySafety outcome
In VigiBase reports, liraglutide was linked to increased suicidal ideation reporting odds.
In plain wordsIn VigiBase reports, liraglutide was linked to increased reporting odds for suicidal thoughts.
Peptide
Liraglutide
Outcome
IncreaseSuicidal ideation reporting
Study
n: not reported in source
Outcome group
Adverse events · Mental health and mood
Studied dose
Dose not stated
Measurements
ROR
4.03 ratio
suicidal ideation
Source sentences
Summary
The RORs for suicidal ideation were significantly increased for semaglutide (5.82), liraglutide (4.03) and tirzepatide (2.25).
2 context sentences(design, population, supporting numbers)
Summary · context
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).
Summary · context
We aimed to characterize the ROR of suicidality associated with GLP-1 RAs, as extrapolated from spontaneous reports.
Show in the study text Report a problemFND-3943313302
03HumanObservational studySafety outcome
In VigiBase reports, tirzepatide was linked to increased suicidal ideation reporting odds.
In plain wordsIn VigiBase reports, tirzepatide was linked to increased reporting odds for suicidal thoughts.
Peptide
Tirzepatide
Outcome
IncreaseSuicidal ideation reporting
Study
n: not reported in source
Outcome group
Adverse events · Mental health and mood
Studied dose
Dose not stated
Measurements
ROR
2.25 ratio
suicidal ideation
Source sentences
Summary
The RORs for suicidal ideation were significantly increased for semaglutide (5.82), liraglutide (4.03) and tirzepatide (2.25).
2 context sentences(design, population, supporting numbers)
Summary · context
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).
Summary · context
We aimed to characterize the ROR of suicidality associated with GLP-1 RAs, as extrapolated from spontaneous reports.
Show in the study text Report a problemFND-3943313303
04HumanObservational studySafety outcome
In VigiBase reports, semaglutide was linked to increased depression/suicidal reporting odds.
In plain wordsIn VigiBase reports, semaglutide was linked to increased depression/suicidal reporting odds.
Peptide
Semaglutide
Outcome
IncreaseDepression/suicidal reporting
Study
n: not reported in source
Outcome group
Adverse events · Mental health and mood
Studied dose
Dose not stated
Measurements
ROR
14.74 ratio
depression/suicidal
Source sentences
Summary
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).
2 context sentences(design, population, supporting numbers)
Summary · context
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).
Summary · context
We aimed to characterize the ROR of suicidality associated with GLP-1 RAs, as extrapolated from spontaneous reports.
Show in the study text Report a problemFND-3943313304
05HumanObservational studySafety outcome
In VigiBase reports, liraglutide was linked to increased depression/suicidal reporting odds.
In plain wordsIn VigiBase reports, liraglutide was linked to increased depression/suicidal reporting odds.
Peptide
Liraglutide
Outcome
IncreaseDepression/suicidal reporting
Study
n: not reported in source
Outcome group
Adverse events · Mental health and mood
Studied dose
Dose not stated
Measurements
ROR
5.86 ratio
depression/suicidal
Source sentences
Summary
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).
2 context sentences(design, population, supporting numbers)
Summary · context
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).
Summary · context
We aimed to characterize the ROR of suicidality associated with GLP-1 RAs, as extrapolated from spontaneous reports.
Show in the study text Report a problemFND-3943313305
06HumanObservational studySafety outcome
In VigiBase reports, semaglutide was linked to increased suicidal behaviour reporting odds.
In plain wordsIn VigiBase reports, semaglutide was linked to increased suicidal behaviour reporting odds.
Peptide
Semaglutide
Outcome
IncreaseSuicidal behaviour reporting
Study
n: not reported in source
Outcome group
Adverse events · Mental health and mood
Studied dose
Dose not stated
Measurements
ROR
6.52 ratio
suicidal behaviour
Source sentences
Summary
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).
2 context sentences(design, population, supporting numbers)
Summary · context
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).
Summary · context
We aimed to characterize the ROR of suicidality associated with GLP-1 RAs, as extrapolated from spontaneous reports.
Show in the study text Report a problemFND-3943313306
07HumanObservational studySafety outcome
In VigiBase reports, liraglutide was linked to increased suicidal behaviour reporting odds.
In plain wordsIn VigiBase reports, liraglutide was linked to increased suicidal behaviour reporting odds.
Peptide
Liraglutide
Outcome
IncreaseSuicidal behaviour reporting
Study
n: not reported in source
Outcome group
Adverse events · Mental health and mood
Studied dose
Dose not stated
Measurements
ROR
3.9 ratio
suicidal behaviour
Source sentences
Summary
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).
2 context sentences(design, population, supporting numbers)
Summary · context
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).
Summary · context
We aimed to characterize the ROR of suicidality associated with GLP-1 RAs, as extrapolated from spontaneous reports.
Show in the study text Report a problemFND-3943313307
08HumanObservational studySafety outcome
In VigiBase reports, semaglutide was linked to decreased suicide attempt reporting odds.
In plain wordsIn VigiBase reports, semaglutide was linked to decreased suicide attempt reporting odds.
Peptide
Semaglutide
Outcome
DecreaseSuicide attempt reporting
Study
n: not reported in source
Outcome group
Adverse events · Mental health and mood
Studied dose
Dose not stated
Measurements
ROR
0.11 ratio
suicide attempts
Source sentences
Summary
However, for suicide attempts, the ROR was significantly decreased for semaglutide (0.11), dulaglutide (0.075), exenatide (0.047) and liraglutide (0.15).
2 context sentences(design, population, supporting numbers)
Summary · context
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).
Summary · context
We aimed to characterize the ROR of suicidality associated with GLP-1 RAs, as extrapolated from spontaneous reports.
Show in the study text Report a problemFND-3943313308
09HumanObservational studySafety outcome
In VigiBase reports, dulaglutide was linked to decreased suicide attempt reporting odds.
In plain wordsIn VigiBase reports, dulaglutide was linked to decreased suicide attempt reporting odds.
Peptide
Dulaglutide (Trulicity)
Outcome
DecreaseSuicide attempt reporting
Study
n: not reported in source
Outcome group
Adverse events · Mental health and mood
Studied dose
Dose not stated
Measurements
ROR
0.075 ratio
suicide attempts
Source sentences
Summary
However, for suicide attempts, the ROR was significantly decreased for semaglutide (0.11), dulaglutide (0.075), exenatide (0.047) and liraglutide (0.15).
2 context sentences(design, population, supporting numbers)
Summary · context
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).
Summary · context
We aimed to characterize the ROR of suicidality associated with GLP-1 RAs, as extrapolated from spontaneous reports.
Show in the study text Report a problemFND-3943313309
10HumanObservational studySafety outcome
In VigiBase reports, liraglutide was linked to decreased suicide attempt reporting odds.
In plain wordsIn VigiBase reports, liraglutide was linked to decreased suicide attempt reporting odds.
Peptide
Liraglutide
Outcome
DecreaseSuicide attempt reporting
Study
n: not reported in source
Outcome group
Adverse events · Mental health and mood
Studied dose
Dose not stated
Measurements
ROR
0.15 ratio
suicide attempts
Source sentences
Summary
However, for suicide attempts, the ROR was significantly decreased for semaglutide (0.11), dulaglutide (0.075), exenatide (0.047) and liraglutide (0.15).
2 context sentences(design, population, supporting numbers)
Summary · context
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).
Summary · context
We aimed to characterize the ROR of suicidality associated with GLP-1 RAs, as extrapolated from spontaneous reports.
Show in the study text Report a problemFND-3943313310
11HumanObservational studySafety outcome
In VigiBase reports, semaglutide was linked to decreased completed suicide reporting odds.
In plain wordsIn VigiBase reports, semaglutide was linked to decreased reporting odds for completed suicide.
Peptide
Semaglutide
Outcome
DecreaseCompleted suicide reporting
Study
n: not reported in source
Outcome group
Mortality · Whole body
Studied dose
Dose not stated
Measurements
ROR
0.01 ratio
completed suicide
Source sentences
Summary
For completed suicide, the ROR was also significantly decreased for semaglutide (0.01), dulaglutide (0.003), exenatide (0.002) and liraglutide (0.008).
2 context sentences(design, population, supporting numbers)
Summary · context
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).
Summary · context
We aimed to characterize the ROR of suicidality associated with GLP-1 RAs, as extrapolated from spontaneous reports.
Show in the study text Report a problemFND-3943313311
12HumanObservational studySafety outcome
In VigiBase reports, dulaglutide was linked to decreased completed suicide reporting odds.
In plain wordsIn VigiBase reports, dulaglutide was linked to decreased reporting odds for completed suicide.
Peptide
Dulaglutide (Trulicity)
Outcome
DecreaseCompleted suicide reporting
Study
n: not reported in source
Outcome group
Mortality · Whole body
Studied dose
Dose not stated
Measurements
ROR
0.003 ratio
completed suicide
Source sentences
Summary
For completed suicide, the ROR was also significantly decreased for semaglutide (0.01), dulaglutide (0.003), exenatide (0.002) and liraglutide (0.008).
2 context sentences(design, population, supporting numbers)
Summary · context
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).
Summary · context
We aimed to characterize the ROR of suicidality associated with GLP-1 RAs, as extrapolated from spontaneous reports.
Show in the study text Report a problemFND-3943313312
13HumanObservational studySafety outcome
In VigiBase reports, liraglutide was linked to decreased completed suicide reporting odds.
In plain wordsIn VigiBase reports, liraglutide was linked to decreased reporting odds for completed suicide.
Peptide
Liraglutide
Outcome
DecreaseCompleted suicide reporting
Study
n: not reported in source
Outcome group
Mortality · Whole body
Studied dose
Dose not stated
Measurements
ROR
0.008 ratio
completed suicide
Source sentences
Summary
For completed suicide, the ROR was also significantly decreased for semaglutide (0.01), dulaglutide (0.003), exenatide (0.002) and liraglutide (0.008).
2 context sentences(design, population, supporting numbers)
Summary · context
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).
Summary · context
We aimed to characterize the ROR of suicidality associated with GLP-1 RAs, as extrapolated from spontaneous reports.
Show in the study text Report a problemFND-3943313313

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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 5Current
22 Oct 2026, 02:25 UTC
Study results updated
Versions 2 to 4
21 Oct 2026, 18:59 UTC
The same notice was added 3 times, first on 9 Oct 2026, 03:06 UTC. The status did not change between them.
Study data updated · source update from Europe PMC
Version 1
9 Oct 2026, 03:04 UTC
First added · source update from Europe PMC