Association of glucagon-like peptide-1 receptor agonists with atrial fibrillation, cardiac arrest, and ventricular fibrillation: Casual evidence from a drug target Mendelian randomization
Abstract Background Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown benefits for cardiorenal outcomes in patients with type 2 diabetes mellitus. Although some observational studies suggest that GLP-1RAs protect against arrhythmias, the evidence remains inconclusive. Methods This stud...
Saved in:
| Main Authors: | , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-05-01
|
| Series: | Diabetology & Metabolic Syndrome |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13098-025-01712-w |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849704711821721600 |
|---|---|
| author | Xinyi Zhang Nanqin Peng Xiaoyue Zhang Zicheng Zhu Yan Miao Yuting Wu Jitao Ling Chen Li Wenli Gu Jing Zhang Abudukeremu Ayiguli Ziheng Zheng Peng Yu Xiao Liu |
| author_facet | Xinyi Zhang Nanqin Peng Xiaoyue Zhang Zicheng Zhu Yan Miao Yuting Wu Jitao Ling Chen Li Wenli Gu Jing Zhang Abudukeremu Ayiguli Ziheng Zheng Peng Yu Xiao Liu |
| author_sort | Xinyi Zhang |
| collection | DOAJ |
| description | Abstract Background Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown benefits for cardiorenal outcomes in patients with type 2 diabetes mellitus. Although some observational studies suggest that GLP-1RAs protect against arrhythmias, the evidence remains inconclusive. Methods This study aimed to assess the causal relationship between GLP-1RAs and arrhythmias, including atrial fibrillation (AF), cardiac arrest, and ventricular fibrillation. We performed a two-sample Mendelian randomization (MR) analysis to examine the associations between genetically proxied GLP-1RAs and the risk of arrhythmias. Genetic instruments for GLP-1RAs were obtained from the cis-expression quantitative trait loci of the GLP1R gene, on the basis of data from the eQTLGen Consortium. Genome-wide association study (GWAS) data for AF were sourced from FinnGen10, whereas data for cardiac arrest and ventricular fibrillation came from the GWAS Catalog. Bayesian colocalization and multivariable Mendelian randomization (MVMR) analyses were conducted as supplementary analyses. Results Twelve independent single nucleotide polymorphisms were identified as genetic instruments for GLP-1RAs. MR analysis indicated that genetically proxied GLP-1RAs were associated with a reduced risk of AF (odds ratio [OR] = 0.78, 95% confidence interval [CI] = 0.71–0.85, p = 4.45E-08, posterior probability of hypothesis 4 [PP.H4] = 0.007) and a lower risk of cardiac arrest and ventricular fibrillation (OR = 0.60, 95% CI = 0.42–0.85, p = 0.0039, PP.H4 = 0.018). Bayesian colocalization analysis revealed that genetically proxied GLP-1RAs did not share genetic variation with arrhythmias. MVMR analysis revealed that, after adjusting for body mass index and type 2 diabetes mellitus, genetically proxied GLP-1RAs did not have a significant effect on the risk of arrhythmias. Conclusions Our findings suggest that genetically proxied GLP-1RAs are causally associated with a reduced risk of AF, cardiac arrest, and ventricular fibrillation. Further randomized controlled trials are needed to confirm these results. |
| format | Article |
| id | doaj-art-dcc8fcdcfa5f4fe2bce672aaa1745743 |
| institution | DOAJ |
| issn | 1758-5996 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Diabetology & Metabolic Syndrome |
| spelling | doaj-art-dcc8fcdcfa5f4fe2bce672aaa17457432025-08-20T03:16:41ZengBMCDiabetology & Metabolic Syndrome1758-59962025-05-0117111010.1186/s13098-025-01712-wAssociation of glucagon-like peptide-1 receptor agonists with atrial fibrillation, cardiac arrest, and ventricular fibrillation: Casual evidence from a drug target Mendelian randomizationXinyi Zhang0Nanqin Peng1Xiaoyue Zhang2Zicheng Zhu3Yan Miao4Yuting Wu5Jitao Ling6Chen Li7Wenli Gu8Jing Zhang9Abudukeremu Ayiguli10Ziheng Zheng11Peng Yu12Xiao Liu13Department of Endocrinology and Metabolism, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityDepartment of Endocrinology and Metabolism, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityDepartment of Endocrinology and Metabolism, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityDepartment of Anesthesiology, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityDepartment of Endocrinology and Metabolism, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityDepartment of Endocrinology and Metabolism, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityDepartment of Endocrinology and Metabolism, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityDepartment of Pharmacy, the First Affiliated Hospital of Guangxi Medical UniversityCardiology Division, Department of Medicine, Queen Mary Hospital, The University of Hong KongDepartment of Anesthesiology, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityDepartment of Cardiology, Sun Yat-sen Memorial Hospital of Sun Yat-sen UniversityDepartment of Cardiology, Sun Yat-sen Memorial Hospital of Sun Yat-sen UniversityDepartment of Endocrinology and Metabolism, the Second Affiliated Hospital, Jiangxi Medical College, Nanchang UniversityDepartment of Cardiology, Sun Yat-sen Memorial Hospital of Sun Yat-sen UniversityAbstract Background Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown benefits for cardiorenal outcomes in patients with type 2 diabetes mellitus. Although some observational studies suggest that GLP-1RAs protect against arrhythmias, the evidence remains inconclusive. Methods This study aimed to assess the causal relationship between GLP-1RAs and arrhythmias, including atrial fibrillation (AF), cardiac arrest, and ventricular fibrillation. We performed a two-sample Mendelian randomization (MR) analysis to examine the associations between genetically proxied GLP-1RAs and the risk of arrhythmias. Genetic instruments for GLP-1RAs were obtained from the cis-expression quantitative trait loci of the GLP1R gene, on the basis of data from the eQTLGen Consortium. Genome-wide association study (GWAS) data for AF were sourced from FinnGen10, whereas data for cardiac arrest and ventricular fibrillation came from the GWAS Catalog. Bayesian colocalization and multivariable Mendelian randomization (MVMR) analyses were conducted as supplementary analyses. Results Twelve independent single nucleotide polymorphisms were identified as genetic instruments for GLP-1RAs. MR analysis indicated that genetically proxied GLP-1RAs were associated with a reduced risk of AF (odds ratio [OR] = 0.78, 95% confidence interval [CI] = 0.71–0.85, p = 4.45E-08, posterior probability of hypothesis 4 [PP.H4] = 0.007) and a lower risk of cardiac arrest and ventricular fibrillation (OR = 0.60, 95% CI = 0.42–0.85, p = 0.0039, PP.H4 = 0.018). Bayesian colocalization analysis revealed that genetically proxied GLP-1RAs did not share genetic variation with arrhythmias. MVMR analysis revealed that, after adjusting for body mass index and type 2 diabetes mellitus, genetically proxied GLP-1RAs did not have a significant effect on the risk of arrhythmias. Conclusions Our findings suggest that genetically proxied GLP-1RAs are causally associated with a reduced risk of AF, cardiac arrest, and ventricular fibrillation. Further randomized controlled trials are needed to confirm these results.https://doi.org/10.1186/s13098-025-01712-wGlucagon-like peptide-1 receptor agonistsAtrial fibrillationCardiac arrestVentricular fibrillationMendelian randomization |
| spellingShingle | Xinyi Zhang Nanqin Peng Xiaoyue Zhang Zicheng Zhu Yan Miao Yuting Wu Jitao Ling Chen Li Wenli Gu Jing Zhang Abudukeremu Ayiguli Ziheng Zheng Peng Yu Xiao Liu Association of glucagon-like peptide-1 receptor agonists with atrial fibrillation, cardiac arrest, and ventricular fibrillation: Casual evidence from a drug target Mendelian randomization Diabetology & Metabolic Syndrome Glucagon-like peptide-1 receptor agonists Atrial fibrillation Cardiac arrest Ventricular fibrillation Mendelian randomization |
| title | Association of glucagon-like peptide-1 receptor agonists with atrial fibrillation, cardiac arrest, and ventricular fibrillation: Casual evidence from a drug target Mendelian randomization |
| title_full | Association of glucagon-like peptide-1 receptor agonists with atrial fibrillation, cardiac arrest, and ventricular fibrillation: Casual evidence from a drug target Mendelian randomization |
| title_fullStr | Association of glucagon-like peptide-1 receptor agonists with atrial fibrillation, cardiac arrest, and ventricular fibrillation: Casual evidence from a drug target Mendelian randomization |
| title_full_unstemmed | Association of glucagon-like peptide-1 receptor agonists with atrial fibrillation, cardiac arrest, and ventricular fibrillation: Casual evidence from a drug target Mendelian randomization |
| title_short | Association of glucagon-like peptide-1 receptor agonists with atrial fibrillation, cardiac arrest, and ventricular fibrillation: Casual evidence from a drug target Mendelian randomization |
| title_sort | association of glucagon like peptide 1 receptor agonists with atrial fibrillation cardiac arrest and ventricular fibrillation casual evidence from a drug target mendelian randomization |
| topic | Glucagon-like peptide-1 receptor agonists Atrial fibrillation Cardiac arrest Ventricular fibrillation Mendelian randomization |
| url | https://doi.org/10.1186/s13098-025-01712-w |
| work_keys_str_mv | AT xinyizhang associationofglucagonlikepeptide1receptoragonistswithatrialfibrillationcardiacarrestandventricularfibrillationcasualevidencefromadrugtargetmendelianrandomization AT nanqinpeng associationofglucagonlikepeptide1receptoragonistswithatrialfibrillationcardiacarrestandventricularfibrillationcasualevidencefromadrugtargetmendelianrandomization AT xiaoyuezhang associationofglucagonlikepeptide1receptoragonistswithatrialfibrillationcardiacarrestandventricularfibrillationcasualevidencefromadrugtargetmendelianrandomization AT zichengzhu associationofglucagonlikepeptide1receptoragonistswithatrialfibrillationcardiacarrestandventricularfibrillationcasualevidencefromadrugtargetmendelianrandomization AT yanmiao associationofglucagonlikepeptide1receptoragonistswithatrialfibrillationcardiacarrestandventricularfibrillationcasualevidencefromadrugtargetmendelianrandomization AT yutingwu associationofglucagonlikepeptide1receptoragonistswithatrialfibrillationcardiacarrestandventricularfibrillationcasualevidencefromadrugtargetmendelianrandomization AT jitaoling associationofglucagonlikepeptide1receptoragonistswithatrialfibrillationcardiacarrestandventricularfibrillationcasualevidencefromadrugtargetmendelianrandomization AT chenli associationofglucagonlikepeptide1receptoragonistswithatrialfibrillationcardiacarrestandventricularfibrillationcasualevidencefromadrugtargetmendelianrandomization AT wenligu associationofglucagonlikepeptide1receptoragonistswithatrialfibrillationcardiacarrestandventricularfibrillationcasualevidencefromadrugtargetmendelianrandomization AT jingzhang associationofglucagonlikepeptide1receptoragonistswithatrialfibrillationcardiacarrestandventricularfibrillationcasualevidencefromadrugtargetmendelianrandomization AT abudukeremuayiguli associationofglucagonlikepeptide1receptoragonistswithatrialfibrillationcardiacarrestandventricularfibrillationcasualevidencefromadrugtargetmendelianrandomization AT zihengzheng associationofglucagonlikepeptide1receptoragonistswithatrialfibrillationcardiacarrestandventricularfibrillationcasualevidencefromadrugtargetmendelianrandomization AT pengyu associationofglucagonlikepeptide1receptoragonistswithatrialfibrillationcardiacarrestandventricularfibrillationcasualevidencefromadrugtargetmendelianrandomization AT xiaoliu associationofglucagonlikepeptide1receptoragonistswithatrialfibrillationcardiacarrestandventricularfibrillationcasualevidencefromadrugtargetmendelianrandomization |