{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T12:34:00Z","timestamp":1793795640225,"version":"4.6.1"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T00:00:00Z","timestamp":1788825600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,11,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) carry side-effects such as dizziness and nausea related to increased vagal tone. This study investigated associations between GLP-1 RA use and the risk of vagal activity-related (VAR) events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Using the Danish health registers, patients with type 2 diabetes mellitus (T2DM) first-time initiated on GLP-1 RAs (exposure) or sodium-glucose cotransporter-2 inhibitors (SGLT-2i) (active control) were identified between January 2010 and October 2022. Standardized 1-year absolute risks of VAR events (syncope, fractures, bradyarrhythmia, or cardiac device implantation) were computed to compare risk associated with GLP-1 RA and SGLT-2i initiation. Complementary analyses in patients treated for obesity were performed as well. During the study period, 50 076 and 73 138 patients with T2DM were initiated on GLP-1 RA [47% women, median age: 59 years (interquartile range {IQR}: 50\u201368)] or SGLT-2i [39% women, median age: 64 years (IQR: 55\u201372)]. Comorbidity was equally prevalent. The standardized 1-year absolute risk of syncope was 0.58% [95% confidence interval (CI): 0.51\u20130.66%] among patients initiated on GLP-1 RA and comparable to patients initiated on SGLT-2i [0.56% (95% CI: 0.50\u20130.62%)]. One-year risks of fractures, bradyarrhythmia, and cardiac device implantation were equally low and with corresponding standardized risk ratios of 0.90 (95% CI: 0.79\u20131.01), 0.97 (95% CI: 0.67\u20131.28), and 0.86 (95% CI: 0.62\u20131.10), respectively. No associations were found in the group treated for obesity either.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In nationwide cohorts of patients treated for T2DM or obesity, initiation of GLP-1 RA was not associated with an elevated risk of VAR events. Despite a proposed argumentation of vagal activity, GLP-1 RA use was not associated with an increased risk in real-life users.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ehjcvp\/pvag072","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T11:25:33Z","timestamp":1788780333000},"page":"546-555","source":"Crossref","is-referenced-by-count":1,"title":["Vagal activity-related events and glucagon-like peptide-1 receptor agonists"],"prefix":"10.1093","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-0813-0661","authenticated-orcid":false,"given":"Lina","family":"Al-Ansary","sequence":"first","affiliation":[{"name":"Department of Cardiology, Copenhagen University Hospital \u2013 Herlev and Gentofte , Gentofte, Borgmester Ib Juuls Vej 1, Herlev DK-2730 ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3157-8468","authenticated-orcid":false,"given":"Sebastian","family":"Kinnberg Nielsen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Copenhagen University Hospital \u2013 Herlev and Gentofte , Gentofte, Borgmester Ib Juuls Vej 1, Herlev DK-2730 ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3423-5495","authenticated-orcid":false,"given":"Mads","family":"Hashiba Jensen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Copenhagen University Hospital \u2013 Herlev and Gentofte , Gentofte, Borgmester Ib Juuls Vej 1, Herlev DK-2730 ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4891-7358","authenticated-orcid":false,"given":"Nina","family":"Nouhravesh","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Copenhagen University Hospital \u2013 Herlev and Gentofte , Gentofte, Borgmester Ib Juuls Vej 1, Herlev DK-2730 ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9130-3506","authenticated-orcid":false,"given":"Caroline","family":"Sindet-Pedersen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Copenhagen University Hospital \u2013 Herlev and Gentofte , Gentofte, Borgmester Ib Juuls Vej 1, Herlev DK-2730 ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0548-402X","authenticated-orcid":false,"given":"Gunnar","family":"Gislason","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Copenhagen University Hospital \u2013 Herlev and Gentofte , Gentofte, Borgmester Ib Juuls Vej 1, Herlev DK-2730 ,","place":["Denmark"]},{"name":"Department of Clinical Medicine, University of Copenhagen , Blegdamsvej 3B, Copenhagen S 2200 ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4593-3854","authenticated-orcid":false,"given":"Peter","family":"Vibe Rasmussen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Rigshospitalet , Inge Lehmanns Vej 7, Copenhagen \u00d8 2100 ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9827-440X","authenticated-orcid":false,"given":"Morten","family":"Lamberts","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Copenhagen University Hospital \u2013 Herlev and Gentofte , Gentofte, Borgmester Ib Juuls Vej 1, Herlev DK-2730 ,","place":["Denmark"]},{"name":"Department of Clinical Medicine, University of Copenhagen , Blegdamsvej 3B, Copenhagen S 2200 ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8196-2599","authenticated-orcid":false,"given":"Anders","family":"Holt","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Copenhagen University Hospital \u2013 Herlev and Gentofte , Gentofte, Borgmester Ib Juuls Vej 1, Herlev DK-2730 ,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,9,8]]},"reference":[{"key":"2026110318515116700_pvag072-B1","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1007\/s00228-025-03823-9","article-title":"Prescribing patterns of glucagon-like peptide-1 receptor agonists in the Swedish capital region\u2014a register-based cross-sectional study","volume":"81","author":"Fors","year":"2025","journal-title":"Eur J Clin Pharmacol"},{"key":"2026110318515116700_pvag072-B2","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1056\/NEJMoa2032183","article-title":"Once-weekly semaglutide in adults with overweight or obesity","volume":"384","author":"Wilding","year":"2021","journal-title":"N Engl J Med"},{"key":"2026110318515116700_pvag072-B3","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1056\/NEJMoa1901118","article-title":"Oral semaglutide and cardiovascular outcomes in patients with type 2 diabetes","volume":"381","author":"Husain","year":"2019","journal-title":"N Engl J Med"},{"key":"2026110318515116700_pvag072-B4","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1056\/NEJMoa2107519","article-title":"Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes","volume":"385","author":"Fr\u00edas","year":"2021","journal-title":"N Engl J Med"},{"key":"2026110318515116700_pvag072-B5","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1093\/cvr\/cvq271","article-title":"GLP-1 receptor stimulation depresses heart rate variability and inhibits neurotransmission to cardiac vagal neurons","volume":"89","author":"Griffioen","year":"2011","journal-title":"Cardiovasc Res"},{"key":"2026110318515116700_pvag072-B6","doi-asserted-by":"crossref","first-page":"323","DOI":"10.3390\/endocrines5030023","article-title":"Glucagon-like peptide-1 receptor agonists: are they as good as they seem? A systematic review of severe adverse effects","volume":"5","author":"Sharma","year":"2024","journal-title":"Endocrines"},{"key":"2026110318515116700_pvag072-B7","first-page":"717","article-title":"The Danish unique personal identifier and the Danish civil registration system as a tool for research and quality improvement","volume":"31","author":"Mainz","year":"2019","journal-title":"Int J Qual Health Care"},{"key":"2026110318515116700_pvag072-B8","doi-asserted-by":"crossref","first-page":"449","DOI":"10.2147\/CLEP.S91125","article-title":"The Danish National Patient Registry: a review of content, data quality, and research potential","volume":"7","author":"Schmidt","year":"2015","journal-title":"Clin Epidemiol"},{"key":"2026110318515116700_pvag072-B9","doi-asserted-by":"crossref","first-page":"e5","DOI":"10.1016\/j.hrthm.2025.09.044","article-title":"Long-term prognosis in early-onset atrial fibrillation without overt cardiovascular disease","volume":"23","author":"Holt","year":"2026","journal-title":"Heart Rhythm"},{"key":"2026110318515116700_pvag072-B10","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1093\/eurheartj\/ehad834","article-title":"Cannabis for chronic pain: cardiovascular safety in a nationwide Danish study","volume":"45","author":"Holt","year":"2024","journal-title":"Eur Heart J"},{"key":"2026110318515116700_pvag072-B11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/EDE.0000000000001666","article-title":"Validation of the \u201cindication for use\u201d (INDO) variable in the Danish National Prescription Registry","volume":"35","author":"Harbi","year":"2024","journal-title":"Epidemiology"},{"key":"2026110318515116700_pvag072-B12","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s40471-015-0053-5","article-title":"The active comparator, new user study design in pharmacoepidemiology: historical foundations and contemporary application","volume":"2","author":"Lund","year":"2015","journal-title":"Curr Epidemiol Rep"},{"key":"2026110318515116700_pvag072-B13","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1093\/ije\/dyp334","article-title":"Illustrating bias due to conditioning on a collider","volume":"39","author":"Cole","year":"2010","journal-title":"Int J Epidemiol"},{"key":"2026110318515116700_pvag072-B14","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1002\/bimj.201800298","article-title":"On the estimation of average treatment effects with right-censored time to event outcome and competing risks","volume":"62","author":"Ozenne","year":"2020","journal-title":"Biometrical J"},{"key":"2026110318515116700_pvag072-B15","author":"Hern\u00e1n"},{"key":"2026110318515116700_pvag072-B16","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.1016\/j.jacc.2024.03.375","article-title":"Long-term cardiovascular risk associated with treatment of attention-deficit\/hyperactivity disorder in adults","volume":"83","author":"Holt","year":"2024","journal-title":"J Am Coll Cardiol"},{"key":"2026110318515116700_pvag072-B17","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1161\/CIRCOUTCOMES.110.957951","article-title":"Landmark analysis at the 25-year landmark point","volume":"4","author":"Dafni","year":"2011","journal-title":"Circ Cardiovasc Qual Outcomes"},{"key":"2026110318515116700_pvag072-B18","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1056\/NEJMoa1607141","article-title":"Semaglutide and cardiovascular outcomes in patients with type 2 diabetes","volume":"375","author":"Marso","year":"2016","journal-title":"N Engl J Med"},{"key":"2026110318515116700_pvag072-B19","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1056\/NEJMoa1603827","article-title":"Liraglutide and cardiovascular outcomes in type 2 diabetes","volume":"375","author":"Marso","year":"2016","journal-title":"Drug Ther Bull"},{"key":"2026110318515116700_pvag072-B20","doi-asserted-by":"crossref","first-page":"2221","DOI":"10.1056\/NEJMoa2307563","article-title":"Semaglutide and cardiovascular outcomes in obesity without diabetes","volume":"389","author":"Lincoff","year":"2023","journal-title":"N Engl J Med"},{"key":"2026110318515116700_pvag072-B21","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1186\/s12933-022-01492-x","article-title":"Mechanisms underlying the blood pressure lowering effects of dapagliflozin, exenatide, and their combination in people with type 2 diabetes: a secondary analysis of a randomized trial","volume":"21","author":"van Ruiten","year":"2022","journal-title":"Cardiovasc Diabetol"},{"key":"2026110318515116700_pvag072-B22","doi-asserted-by":"crossref","first-page":"E41","DOI":"10.1161\/HYPERTENSIONAHA.123.22022","article-title":"Tirzepatide reduces 24-hour ambulatory blood pressure in adults with body mass index \u226527 kg\/m2: SURMOUNT-1 Ambulatory Blood Pressure Monitoring Substudy","volume":"81","author":"de Lemos","year":"2024","journal-title":"Hypertension"},{"key":"2026110318515116700_pvag072-B23","doi-asserted-by":"crossref","first-page":"882998","DOI":"10.3389\/fendo.2022.882998","article-title":"The risk of major osteoporotic fractures with GLP-1 receptor agonists when compared to DPP-4 inhibitors: a Danish nationwide cohort study","volume":"13","author":"Al-Mashhadi","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"key":"2026110318515116700_pvag072-B24","doi-asserted-by":"crossref","first-page":"134","DOI":"10.26502\/acbr.50170231","article-title":"The effects of glucagon-like peptide-1 receptor agonists of liraglutide on bone turnover makers among type 2 diabetes mellitus patients: a meta-analysis of randomized controlled trials","volume":"06","author":"Kang","year":"2022","journal-title":"Arch Clin Biomed Res"},{"key":"2026110318515116700_pvag072-B25","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1007\/s11657-026-01657-1","article-title":"Midlife physical activity, BMI, and hip fracture risk five decades later in men: a NOREPOS study","volume":"21","author":"Landgraff","year":"2026","journal-title":"Arch Osteoporos"},{"key":"2026110318515116700_pvag072-B26","first-page":"798","article-title":"Data resource profile: the Danish National Prescription Registry","volume":"46","author":"Potteg\u00e5rd","year":"2017","journal-title":"Int J Epidemiol"},{"key":"2026110318515116700_pvag072-B27","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1093\/ehjcvp\/pvad086","article-title":"New-onset syncope in diabetic patients treated with sodium-glucose cotransporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors: a Chinese population-based cohort study","volume":"10","author":"Gao","year":"2024","journal-title":"Eur Heart J Cardiovasc Pharmacother"}],"container-title":["European Heart Journal - Cardiovascular Pharmacotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ehjcvp\/advance-article-pdf\/doi\/10.1093\/ehjcvp\/pvag072\/70997105\/pvag072.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ehjcvp\/article-pdf\/12\/7\/546\/70997105\/pvag072.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ehjcvp\/article-pdf\/12\/7\/546\/70997105\/pvag072.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T23:52:01Z","timestamp":1793749921000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ehjcvp\/article\/12\/7\/546\/8788047"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,8]]},"references-count":27,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,9,8]]},"published-print":{"date-parts":[[2026,11,4]]}},"URL":"https:\/\/doi.org\/10.1093\/ehjcvp\/pvag072","relation":{},"ISSN":["2055-6837","2055-6845"],"issn-type":[{"value":"2055-6837","type":"print"},{"value":"2055-6845","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,11]]},"published":{"date-parts":[[2026,9,8]]}}}