Depression following the initiation of glucagon‐like‐peptide‐1 receptor agonist therapy:   A multinational self‐controlled case series study

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

doi:10.1111/joim.70098

Depression following the initiation of glucagon‐like‐peptide‐1 receptor agonist therapy: A multinational self‐controlled case series study

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

^*Corresponding author for this work

The Chinese University of Hong Kong
National Cheng Kung University
Queen Mary Hospital

Research output: Contribution to journal › Letter, comment/opinion or interview › peer-review

Abstract

Glucagon-like-peptide-1 receptor agonists (GLP-1RAs) are increasingly used as adjunctive treatment in type-2 diabetes and weight management in obesity. However, prior case reports suggested possible neuropsychiatric side effects, potentially linked to glucagon-like-peptide-1 receptor expression in the brain. Consequently, the European Medicines Agency initiated a safety review on the possible association between GLP-1RAs and suicidal thoughts or self-harm [1]. The US Food and Drug Administration (FDA) recommends monitoring for depression or suicidal thoughts and includes warnings concerning suicidal behaviour for some GLP1-RA formulations.

Original language	English
Number of pages	5
Journal	Journal of Internal Medicine
DOIs	https://doi.org/10.1111/joim.70098
Publication status	E-pub ahead of print - 16 Apr 2026

Bibliographical note

© 2026 The Author(s). Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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 (Huang-Tz Ou) on request. HK and UK sites: The underlying data supporting this analysis cannot be directly shared as they are obtained under licence 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.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

multinational
depression
glucagon‐like‐peptide‐1 receptor agonist
self‐controlled case series

Access to Document

10.1111/joim.70098Licence: CC BY 4.0

Journal of Internal Medicine - 2026 - Yan - Depression following the initiation of glucagon‐like‐peptide‐1 receptor agonist
© 2026 The Author(s). Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Final published version, 238 KBLicence: CC BY 4.0

Cite this

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title = "Depression following the initiation of glucagon‐like‐peptide‐1 receptor agonist therapy: A multinational self‐controlled case series study",

abstract = "Glucagon-like-peptide-1 receptor agonists (GLP-1RAs) are increasingly used as adjunctive treatment in type-2 diabetes and weight management in obesity. However, prior case reports suggested possible neuropsychiatric side effects, potentially linked to glucagon-like-peptide-1 receptor expression in the brain. Consequently, the European Medicines Agency initiated a safety review on the possible association between GLP-1RAs and suicidal thoughts or self-harm [1]. The US Food and Drug Administration (FDA) recommends monitoring for depression or suicidal thoughts and includes warnings concerning suicidal behaviour for some GLP1-RA formulations.",

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AU - Wan, Eric Yuk Fai

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