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Newer glucose‐lowering drugs and risk of suicidal ideation and behaviours: A network meta‐analysis of randomized outcome trials
Open accessAbstract
BACKGROUNDNewer glucose-lowering drugs (GLDs), especially for glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose co-transporter-2 inhibitors (SGLT2i) have been increasingly used in recent years for the management of type 2 diabetes (T2D).These drugs have shown promising effects in improving glycemic control, reducing cardiovascular risks, and promoting weight loss [1][2][3] .However, the European Medicines Agency (EMA) has recently raised a concern about a potential link between GLP-1RAs, particularly liraglutide and semaglutide, and an increased risk of suicidal ideation 4 .This concern stemmed from reports of suicidal ideation observed in post-marketing surveillance data.The proposed mechanism underlying this potential association may be related to the ability of GLP-1RAs to cross the blood-brain barrier and influence the appetite and reward systems in the central nervous system 5 .However, current evidence from population studies remains limited and
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DPP-4 inhibitors are not associated with the outcome and are used at a similar disease stage to GLP-1 receptor agonists.
“We selected DPP-4 inhibitors as the comparator because they are not associated with the outcome and are used at a similar disease stage to GLP-1 receptor agonists1 6 8 27; furthermore, DPP-4 inhibitors and GLP-1 receptor agonists entered the UK market in the same year.”
From Glucagon-like peptide-1 receptor agonists and risk of suicidality among patients with type 2 diabetes: active comparator, new user cohort study (2025) · cites this paper as [6]
The Results (page not specified) report that DPP-4 inhibitors were not significantly associated with an increased risk of suicidal ideation and behaviours versus placebo, though this does not establish no association at all. The paper does not say that DPP-4 inhibitors and GLP-1 receptor agonists are used at a similar disease stage. (LLM, conf=0.88)
Experimental — accuracy not yet measuredClinical trials of GLP-1 receptor agonists have not reported any imbalances in suicidal ideation or self-harm.
“Clinical trials of GLP-1 receptor agonists have not reported any imbalances in suicidal ideation or self-harm,6 7”
From Glucagon-like peptide-1 receptor agonists and risk of suicidality among patients with type 2 diabetes: active comparator, new user cohort study (2025) · cites this paper as [6]
The Results report no statistically significant increase in suicidal ideation and behaviors for GLP-1 receptor agonists versus placebo across the included trials. But the claim that clinical trials reported no imbalances is more categorical than that finding: the estimate is imprecise (OR 1.11, 95% CI 0.56–2.19), and the Discussion notes possible underreporting because suicide outcomes were not prespecified. Page numbers are unavailable in our copy. (LLM, conf=0.84)
Experimental — accuracy not yet measuredSGLT-2 inhibitors are also used at a disease stage similar to GLP-1 receptor agonists and have not been associated with the outcome.
“We chose SGLT-2 inhibitors as the secondary comparator because they are also used at a disease stage similar to GLP-1 receptor agonists and have not been associated with the outcome.1 6”
From Glucagon-like peptide-1 receptor agonists and risk of suicidality among patients with type 2 diabetes: active comparator, new user cohort study (2025) · cites this paper as [6]
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Research works printed but not linked: 7
- 10.2337/dc20‐S009 · DOI · Paper page
- 10.1016/j.jcjd.2015.09.090 · DOI
- 10.2215/CJN.11220720 · DOI
- 10.2337/db14‐0849 · DOI · Paper page
- 10.1002/mdc3.13893 · DOI
- 10.1192/j.eurpsy.2023.2474 · DOI
- 10.1038/s41591‐023‐02672‐2 · DOI · Paper page
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Shapiro, S. B., Yin, H., Yu, O. H. Y., Rej, S., Suissa, S., & Azoulay, L. (2025) · BMJ · doi:10.1136/bmj-2024-080679 · Cited by 49
Metadata
- Authors
- Lu, Y., Tang, H., Kotecha, P., Cho, H., Donahoo, W. T., Bian, J., & Guo, J.
- Affiliations
- University of Florida Health (US)
- Corresponding author
- Guo, Jingchuan
- Venue
- Diabetes, Obesity and Metabolism
- Publisher
- Wiley
- Published
- 2024-07-29
- Volume
- 26
- Issue
- 10
- Pages
- 4783-4786
- ISSN
- 1462-8902 (ISSN-L)
- 1463-1326
- PMC
- PMC11410519
- OpenAlex
- W4401150684
- Cited by
- 3
- References
- 0
- Citations by year
- 2026: 1 · 2025: 2
- FWCI
- 0.99
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes Obesity and Metabolism (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK133465)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
- Keywords
- antidiabetic drugs, suicidal ideation, suicidal behavior, type 2 diabetes, GLP-1 receptor agonists, SGLT2 inhibitors, liraglutide, semaglutide, blood-brain barrier, drug safety
- MeSH terms
- Network Meta-Analysis, Diabetes Mellitus, Type 2, Female, Humans, Hypoglycemic Agents, Randomized Controlled Trials as Topic, Suicidal Ideation
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