Use of GLP-1 receptor agonists and risks of suicide attempts or self-harm in patients with type 2 diabetes: a multicountry self-control case series study

Zi-Yang Peng; Vincent Ka Chun Yan; Vincent Kai Chung Wong; Ian Chi Kei Wong; Esther Wai Yin Chan; Eric Yuk Fai Wan; Huang-Tz Ou

doi:10.1136/bmjment-2025-301635

Use of GLP-1 receptor agonists and risks of suicide attempts or self-harm in patients with type 2 diabetes: a multicountry self-control case series study

Zi-Yang Peng
, Vincent Ka Chun Yan
, Vincent Kai Chung Wong
, Ian Chi Kei Wong
, Esther Wai Yin Chan
, Eric Yuk Fai Wan^*
, Huang-Tz Ou^*

^*Corresponding author for this work

Aston Pharmacy School

Department of Pharmacy, Queen Mary Hospital, Hong Kong SAR, China.
The University of Hong Kong, Shenzhen Institute of Research and Innovation, Shenzhen, China.
Department of Family Medicine and Primary Care, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.

Research output: Contribution to journal › Article › peer-review

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Abstract

Background: Inconclusive findings regarding the association between suicidal ideation/suicide attempt and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been recently revealed in a small number of studies.

Methods: This was a multinational self-controlled case series analysis using Hong Kong’s Clinical Data Analysis and Reporting System (2008−2023), Taiwan’s National Health Insurance Research Database (2012−2020) and the UK’s IQVIA Medical Research Database with The Health Improvement Network (2000−2021). A total of 642 suicide attempt or self-harm cases with GLP-1RA use were included to assess pooled incident rate ratios (IRRs) of suicide attempts or self-harm associated with GLP-1RA treatment versus non-treatment with their 95% CIs.

Results: The pooled IRR (95% CI) of suicide attempts or self-harm associated with GLP-1RA treatment versus non-treatment was 0.67 (0.51 to 0.88). The suicide attempt or self-harm risk varied with the time window of GLP-1RA use, with pooled IRRs (95% CIs) of 1.94 (0.86 to 4.37), 0.61 (0.23 to 1.63), 0.72 (0.37 to 1.41), 0.60 (0.32 to 1.09) and 0.63 (0.49 to 0.87) for the pretreatment period and Days 1−30, Days 31−90, Days 91−180 and Days>180 of GLP-1RA treatment, respectively. Subgroup analyses by age, sex and individual GLP-1RAs and sensitivity analyses showed no significant increase in the suicide attempt or self-harm risk associated with GLP-1RA use. The point estimate and CI of the E-value for suicide attempts or self-harm were 2.35 and 1.53, respectively.

Conclusions: We found no increase in the risks of suicide attempts or self-harm following GLP-1RA treatment, and even in the long-term use of GLP-1RAs. Close monitoring of potential suicide attempts or self-harm and ensuring treatment tolerability during treatment initiation are required, and well-controlled or pragmatic trials remain warranted to validate our findings.

Original language	English
Pages (from-to)	1-8
Number of pages	8
Journal	BMJ Mental Health
Volume	28
Issue number	1
DOIs	https://doi.org/10.1136/bmjment-2025-301635
Publication status	Published - 26 Jun 2025

Bibliographical note

Data Access Statement

Data may be obtained from a third party and are not publicly available. Taiwan site: Raw data were generated at Taiwan’s National
Health Insurance Research Database. Derived data supporting the findings of this study are available from the corresponding author (H-TO) on request. HK and UK sites: The underlying data supporting this analysis cannot be directly shared as they are obtained under license from IQVIA (for UK data) and owned by Hospital Authority of Hong Kong (for HK data) and data custodians have not given permission for sharing.

Funding

This study was supported by a grant from the National Science and Technology Council of Taiwan (grant number NSTC 112-2628-B- 006-008-MY3) (recipient: H- TO), and from National Natural Science Foundation of China (NSFC) Excellent Young Scientists Fund (Hong Kong and Macau) (Ref No. 82222902) (recipient: EYFW).

Keywords

Suicide & self-harm

Access to Document

10.1136/bmjment-2025-301635Licence: CC BY-NC 4.0

Z-Y Peng et al_Use of GLP-1 receptor agonists and risks of suicide attempts or self-harm in patients w type 2 diabetes_multicountry self-control case series study
Copyright © Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. Published by BMJ Group.
Final published version, 511 KBLicence: CC BY-NC 4.0

Cite this

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title = "Use of GLP-1 receptor agonists and risks of suicide attempts or self-harm in patients with type 2 diabetes: a multicountry self-control case series study",

abstract = "Background: Inconclusive findings regarding the association between suicidal ideation/suicide attempt and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been recently revealed in a small number of studies. Methods: This was a multinational self-controlled case series analysis using Hong Kong{\textquoteright}s Clinical Data Analysis and Reporting System (2008−2023), Taiwan{\textquoteright}s National Health Insurance Research Database (2012−2020) and the UK{\textquoteright}s IQVIA Medical Research Database with The Health Improvement Network (2000−2021). A total of 642 suicide attempt or self-harm cases with GLP-1RA use were included to assess pooled incident rate ratios (IRRs) of suicide attempts or self-harm associated with GLP-1RA treatment versus non-treatment with their 95\% CIs. Results: The pooled IRR (95\% CI) of suicide attempts or self-harm associated with GLP-1RA treatment versus non-treatment was 0.67 (0.51 to 0.88). The suicide attempt or self-harm risk varied with the time window of GLP-1RA use, with pooled IRRs (95\% CIs) of 1.94 (0.86 to 4.37), 0.61 (0.23 to 1.63), 0.72 (0.37 to 1.41), 0.60 (0.32 to 1.09) and 0.63 (0.49 to 0.87) for the pretreatment period and Days 1−30, Days 31−90, Days 91−180 and Days>180 of GLP-1RA treatment, respectively. Subgroup analyses by age, sex and individual GLP-1RAs and sensitivity analyses showed no significant increase in the suicide attempt or self-harm risk associated with GLP-1RA use. The point estimate and CI of the E-value for suicide attempts or self-harm were 2.35 and 1.53, respectively. Conclusions: We found no increase in the risks of suicide attempts or self-harm following GLP-1RA treatment, and even in the long-term use of GLP-1RAs. Close monitoring of potential suicide attempts or self-harm and ensuring treatment tolerability during treatment initiation are required, and well-controlled or pragmatic trials remain warranted to validate our findings.",

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AU - Peng, Zi-Yang

AU - Yan, Vincent Ka Chun

AU - Wong, Vincent Kai Chung

AU - Wong, Ian Chi Kei

AU - Chan, Esther Wai Yin

AU - Wan, Eric Yuk Fai

AU - Ou, Huang-Tz

PY - 2025/6/26

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N2 - Background: Inconclusive findings regarding the association between suicidal ideation/suicide attempt and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been recently revealed in a small number of studies. Methods: This was a multinational self-controlled case series analysis using Hong Kong’s Clinical Data Analysis and Reporting System (2008−2023), Taiwan’s National Health Insurance Research Database (2012−2020) and the UK’s IQVIA Medical Research Database with The Health Improvement Network (2000−2021). A total of 642 suicide attempt or self-harm cases with GLP-1RA use were included to assess pooled incident rate ratios (IRRs) of suicide attempts or self-harm associated with GLP-1RA treatment versus non-treatment with their 95% CIs. Results: The pooled IRR (95% CI) of suicide attempts or self-harm associated with GLP-1RA treatment versus non-treatment was 0.67 (0.51 to 0.88). The suicide attempt or self-harm risk varied with the time window of GLP-1RA use, with pooled IRRs (95% CIs) of 1.94 (0.86 to 4.37), 0.61 (0.23 to 1.63), 0.72 (0.37 to 1.41), 0.60 (0.32 to 1.09) and 0.63 (0.49 to 0.87) for the pretreatment period and Days 1−30, Days 31−90, Days 91−180 and Days>180 of GLP-1RA treatment, respectively. Subgroup analyses by age, sex and individual GLP-1RAs and sensitivity analyses showed no significant increase in the suicide attempt or self-harm risk associated with GLP-1RA use. The point estimate and CI of the E-value for suicide attempts or self-harm were 2.35 and 1.53, respectively. Conclusions: We found no increase in the risks of suicide attempts or self-harm following GLP-1RA treatment, and even in the long-term use of GLP-1RAs. Close monitoring of potential suicide attempts or self-harm and ensuring treatment tolerability during treatment initiation are required, and well-controlled or pragmatic trials remain warranted to validate our findings.

AB - Background: Inconclusive findings regarding the association between suicidal ideation/suicide attempt and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been recently revealed in a small number of studies. Methods: This was a multinational self-controlled case series analysis using Hong Kong’s Clinical Data Analysis and Reporting System (2008−2023), Taiwan’s National Health Insurance Research Database (2012−2020) and the UK’s IQVIA Medical Research Database with The Health Improvement Network (2000−2021). A total of 642 suicide attempt or self-harm cases with GLP-1RA use were included to assess pooled incident rate ratios (IRRs) of suicide attempts or self-harm associated with GLP-1RA treatment versus non-treatment with their 95% CIs. Results: The pooled IRR (95% CI) of suicide attempts or self-harm associated with GLP-1RA treatment versus non-treatment was 0.67 (0.51 to 0.88). The suicide attempt or self-harm risk varied with the time window of GLP-1RA use, with pooled IRRs (95% CIs) of 1.94 (0.86 to 4.37), 0.61 (0.23 to 1.63), 0.72 (0.37 to 1.41), 0.60 (0.32 to 1.09) and 0.63 (0.49 to 0.87) for the pretreatment period and Days 1−30, Days 31−90, Days 91−180 and Days>180 of GLP-1RA treatment, respectively. Subgroup analyses by age, sex and individual GLP-1RAs and sensitivity analyses showed no significant increase in the suicide attempt or self-harm risk associated with GLP-1RA use. The point estimate and CI of the E-value for suicide attempts or self-harm were 2.35 and 1.53, respectively. Conclusions: We found no increase in the risks of suicide attempts or self-harm following GLP-1RA treatment, and even in the long-term use of GLP-1RAs. Close monitoring of potential suicide attempts or self-harm and ensuring treatment tolerability during treatment initiation are required, and well-controlled or pragmatic trials remain warranted to validate our findings.

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Use of GLP-1 receptor agonists and risks of suicide attempts or self-harm in patients with type 2 diabetes: a multicountry self-control case series study

Abstract

Bibliographical note

Data Access Statement

Funding

Keywords

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