The risk of depression, anxiety, and suicidal behavior in patients with obesity on glucagon like peptide-1 receptor agonist therapy
Open accessAbstract
This large community-based cohort study investigates the impact of glucagon-like peptide-1 receptor agonists (GLP-1 RAs), specifically Liraglutide and Semaglutide, on the risk of developing psychiatric conditions such as depression, anxiety, and suicidal behaviors in patients with obesity. Utilizing post-marketing data, this research compares patients prescribed GLP-1 RAs (cases) with those not taking these medications (controls). The analysis spanned data from January 1, 2015, to December 31, 2023. To minimize selection bias, we employed 1:1 propensity score matching to account for demographic factors such as age, sex, race, and comorbidities. After matching, the study included 162,253 case and control patients. This study showed a significant association between GLP-1 RA treatment and an 98% increased risk of any psychiatric disorders. Notably, patients on GLP-1 RAs exhibited a 195% higher risk of major depression, a 108% increased risk for anxiety, and a 106% elevated risk for suicidal behavior. These findings underscore the critical need for physicians to thoroughly assess patient history before prescribing GLP-1 RAs and highlight the urgent requirement for further prospective clinical trials to fully understand the implications of GLP-1 RA use on mental health in the obese patient population.
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Suicidal ideation is associated with the use of various weight reduction drugs.
“Suicidal ideation is associated with the use of various weight reduction drugs [67,68].”
From Exploring the Side Effects of GLP-1 Receptor Agonist: To Ensure Its Optimal Positioning (2025) · cites this paper as [68]
The Introduction identifies liraglutide and semaglutide as weight-reduction drugs, and the Results report a higher rate of the combined outcome of suicidal ideation or attempts among patients using GLP-1 receptor agonists. The claim extends that finding to weight-reduction drugs generally, which this study does not establish; its reported outcome also does not isolate suicidal ideation. (LLM, conf=0.84)
Experimental — accuracy not yet measuredKornelius et al. reported a three-fold higher risk of major depression, and a doubled risk for anxiety and suicidal behavior in a large retrospective study of GLP-1RA users.
“Kornelius et al. reported a three-fold higher risk of major depression, and a doubled risk for anxiety and suicidal behavior in a large (n = 11,683,623) retrospective study of GLP-1RA users utilizing the TrinetX database (100).”
From The science of safety: adverse effects of GLP-1 receptor agonists as glucose-lowering and obesity medications (2026) · cites this paper as [100]
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- Authors
- Kornelius, E., Huang, J.-Y., Lo, S.-C., Huang, C.-N., & Yang, Y.-S.
- Affiliations
- Chung Shan Medical University Hospital (TW)
- Corresponding author
- Yang, Yi-Sun
- Venue
- Scientific Reports
- Published
- 2024-10-18
- Volume
- 14
- Issue
- 1
- Pages
- 24433-24433
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC11489776
- OpenAlex
- W4403514301
- Cited by
- 143
- References
- 46
- Citations by year
- 2026: 70 · 2025: 68 · 2024: 4 · 2022: 1
- FWCI
- 46.31
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Scientific Reports (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Chung Shan Medical University Hospital (CSH-2020-C-016)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
- Keywords
- GLP-1 receptor agonists, obesity, depression, anxiety, suicidal behavior, psychiatric adverse effects, liraglutide, semaglutide, mental health, drug safety
- MeSH terms
- Liraglutide, Glucagon-Like Peptide-1 Receptor Agonists, Semaglutide, Adult, Aged, Anxiety, Depression, Glucagon-Like Peptides, Female, Humans, Hypoglycemic Agents, Male, Middle Aged, Obesity, Risk Factors, Cohort Studies
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