Glucagon-like-peptide 1 receptor agonism and attempted suicide: A Mendelian randomisation study to assess a potential causal association.

Autor: Nguyen A; Department of Medicine, University Health Network, Toronto, Toronto, Canada., Smith E; Centre for Addiction and Mental Health (CAMH), Toronto, Institute of Medical Science, Department of Psychiatry & Pharmacology, Banting and Best Diabetes Centre (BBDC), University of Toronto, Toronto, Canada., Hashemy H; Department of Medicine, University Health Network, Toronto, Toronto, Canada., Agarwal SM; Centre for Addiction and Mental Health (CAMH), Toronto, Institute of Medical Science, Department of Psychiatry & Pharmacology, Banting and Best Diabetes Centre (BBDC), University of Toronto, Toronto, Canada., Hahn MK; Centre for Addiction and Mental Health (CAMH), Toronto, Institute of Medical Science, Department of Psychiatry & Pharmacology, Banting and Best Diabetes Centre (BBDC), University of Toronto, Toronto, Canada., Paterson AD; Genetics and Genome Biology Program, The Hospital for Sick Children, Toronto, Canada.; Divisions of Epidemiology and Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, Canada., Dash S; Department of Medicine, University Health Network, Toronto, Toronto, Canada.
Jazyk: angličtina
Zdroj: Clinical obesity [Clin Obes] 2024 Aug; Vol. 14 (4), pp. e12676. Date of Electronic Publication: 2024 May 23.
DOI: 10.1111/cob.12676
Abstrakt: Glucagon-like-peptide 1 receptor agonists (GLP-1RA) have transformed type 2 diabetes (T2D) and obesity management. Multiple regulatory agencies are investigating reported associations between GLP1-RA and increased suicide attempts (SA), but observational data may be prone to confounding. Randomised control trials (RCT) of GLP-1RA were largely undertaken in people at lower risk of SA. Real-world data suggest semaglutide use associates with reduced suicidal ideation and depression but was under-powered to statistically assess risk of SA. Mendelian randomisation (MR) leverages genetic instrument(s) to infer potential causal association between an exposure and an outcome. We undertook MR using missense variants in the gene encoding GLP1R that improve glycemia, lower T2D risk and/or lower BMI, to investigate potential causal association between GLP-1RA and SA. In people of European ancestry, MR did not find evidence genetically proxied GLP1RA increased SA in a general population cohort: (rs10305492, exposure: HbA1c, odds ratio [OR] and 95% confidence interval [CI]: 1.38, 0.41-4.62, p = .60), (rs10305492, exposure: FG, OR 1.27, 0.52-3.13, p = .60) and (rs1042044, exposure BMI, OR 0.30, 0.06-1.48) with concordant results in a multi-ancestry SA case-control cohort. In conclusion, we did not find MR evidence that increased GLP-1RA impacts SA. This awaits confirmation with RCT and real-world data.
(© 2024 World Obesity Federation.)
Databáze: MEDLINE
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