Glucagon-Like Peptide-1 Receptor Agonism and Suicide Risk: Evidence From Mendelian Randomization.

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dc.creatorZhao, Sizheng Steven
dc.creatorBurgess, Stephen
dc.creatorGill, Dipender
dc.date2024-05-31T23:31:17Z
dc.date2024-06-18
dc.date.accessioned2026-08-03T02:39:55Z
dc.descriptionGlucagon-like peptide-1 receptor agonists (GLP1Ra) have proven efficacious for treating type 2 diabetes (T2D), obesity, and cardiovascular disease (1). However, suicidal thoughts and self-injury have been reported following treatment with semaglutide, leading to investigations by the European Medicines Agency, and the Medicines and Healthcare Products Regulatory Agency in the United Kingdom. It remains unclear whether these potential adverse events are attributable to semaglutide, the GLP1Ra drug class, the underlying conditions, or other factors. A large observational study found that semaglutide use was associated with lower risk of incident and recurrent suicidal ideation, compared with other anti-obesity or anti-diabetes medications (2). However, it is difficult to draw causal inference from traditional epidemiological associations due to the potential for residual confounding and reverse causation. For this reason, it is important to triangulate evidence using methods that make orthogonal assumptions. Here, we applied Mendelian randomization (MR) to investigate whether there is human genetic evidence for a causal effect of GLP1Ra on suicide risk. This paradigm uses randomly allocated genetic variants as instrumental variables for studying the effect of GLP1Ra, and is therefore less vulnerable to the environmental confounding and reverse causation bias that can hinder causal inference in traditional epidemiological designs.
dc.formatapplication/pdf
dc.formatimage/tiff
dc.identifier2047-9980
dc.identifierhttps://www.repository.cam.ac.uk/handle/1810/369064
dc.identifierhttps://doi.org/10.17863/CAM.109021
dc.identifier2047-9980
dc.identifier.urihttps://repo.dare.co.zw/handle/123456789/168266
dc.languageeng
dc.publisherWolters Kluwer
dc.publisherMrc Biostatistics Unit
dc.publisherhttps://doi.org/10.1161/jaha.124.035948
dc.rightsAttribution 4.0 International
dc.rightshttps://creativecommons.org/licenses/by/4.0/
dc.subjectdiabetes
dc.subjectglucagon‐like peptide‐1 receptor antagonist
dc.subjectobesity
dc.subjectsuicide
dc.subjectweight loss
dc.subjectHumans
dc.subjectGlucagon-Like Peptide-1 Receptor
dc.subjectHypoglycemic Agents
dc.subjectMendelian Randomization Analysis
dc.subjectRisk Assessment
dc.subjectRisk Factors
dc.subjectSuicide
dc.subjectGlucagon-Like Peptide-1 Receptor Agonists
dc.titleGlucagon-Like Peptide-1 Receptor Agonism and Suicide Risk: Evidence From Mendelian Randomization.
dc.typeArticle

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