{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T18:09:53Z","timestamp":1790273393973,"version":"4.1.0"},"reference-count":30,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"\n Introduction<\/jats:title>\n Individuals with co-morbid T2D and IBD represent a uniquely high-risk group, facing amplified cardiovascular risk through synergistic inflammatory and metabolic pathways, in whom conventional cardiometabolic strategies (such as dietary and lifestyle changes, weight loss, blood pressure and lipid optimization, metformin therapy, SGLT2 inhibitor therapy) may be insufficient due to the overlap between metabolic disease and chronic inflammatory disease processes. At present, the literature available on the role of incretin-based therapy in the treatment of T2D in patients with co-morbid IBD is limited. We aimed to evaluate the association of GLP-1 receptor agonists and dual GLP-1\/GIP receptor agonists with cardiovascular outcomes in individuals with T2DM and IBD. This study is not intended as a direct comparison of the efficacy of GLP-1 agonists and dual GLP-1\/GIP receptor agonists in patients with T2D and IBD. Both drug classes were analyzed as a combined incretin-based therapy exposure group to reflect real-world prescribing patterns and maximize statistical power.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We conducted a retrospective cohort study using the TriNetX global federated research network, identifying adults (\u226518 years) with T2D and IBD between 2015\u20132024. Patients prescribed GLP-1 or dual GLP-1\/GIP were compared with non-users following 1:1 propensity score matching on demographics, comorbidities, and medication use. Relative risks (RR) and Hazard Ratios (HR) with 95% confidence intervals (CI) were calculated, with significance defined as p\u2009<\u20090.05.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n After matching 16,118 patients per cohort from among a total matched population of 32,236 patients, GLP-1 or GLP-1\/GIP receptor agonist therapy was associated with lower hazard ratios across all outcomes, including myocardial infarction (HR 0.701, 95% CI 0.637\u20130.771), chronic ischemic heart disease (HR 0.936, 95% CI 0.896\u20130.978), heart failure (HR 0.777, 95% CI 0.737\u20130.820), atrial fibrillation\/flutter (HR 0.838, 95% CI 0.788\u20130.890), sudden cardiac death (HR 0.694, 95% CI 0.605\u20130.795), ischemic stroke (HR 0.781, 95% CI 0.707\u20130.862), deep vein thrombosis (HR 0.642, 95% CI 0.586\u20130.702), and pulmonary embolism (HR 0.722, 95% CI 0.640\u20130.815).<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n In patients with comorbid T2D and IBD, GLP-1 and GLP-1\/GIP receptor agonists were associated with significant reductions in ischemic, arrhythmic, and thromboembolic cardiovascular outcomes. These findings highlight the potential role of incretin-based therapies in improving cardiovascular risk management in this high-risk population. However, the present study does not establish the comparative efficacy of the two classes of drugs in this patient population, and the findings may be associational rather than causal. Both drug classes were analyzed as a combined exposure group. Mechanistic explanations proposed in this paper should be considered hypothesis-generating rather than confirmed by the current observational study design.<\/jats:p>\n <\/jats:sec>","DOI":"10.1371\/journal.pone.0358659","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:32:17Z","timestamp":1790271137000},"page":"e0358659","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cardiovascular outcomes associated With GLP-1 and dual GLP-1\/GIP receptor agonists in patients with type 2 diabetes and inflammatory bowel disease: A retrospective real-world cohort study"],"prefix":"10.1371","volume":"21","author":[{"given":"Muhammad Ali Ibrahim","family":"Kazi","sequence":"first","affiliation":[{"name":"Anne Arundel Medical Center","place":["Annapolis, Maryland, United States of America"],"department":["Department of Internal Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed Musa","family":"Mufarrih","sequence":"additional","affiliation":[{"name":"Aga Khan University","place":["Karachi, Pakistan"],"department":["Department of Internal Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4184-3097","authenticated-orcid":true,"given":"Akanksha","family":"Sirohi","sequence":"additional","affiliation":[{"name":"Anne Arundel Medical Center","place":["Annapolis, Maryland, United States of America"],"department":["Department of Internal Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fahad","family":"Hasan","sequence":"additional","affiliation":[{"name":"CMH Lahore Medial College and Institute of Dentistry","place":["Lahore, Pakistan"],"department":["Department of Internal Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akshay","family":"Sharma","sequence":"additional","affiliation":[{"name":"Anne Arundel Medical Center","place":["Annapolis, Maryland, United States of America"],"department":["Department of Internal Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanmeet","family":"Singh","sequence":"additional","affiliation":[{"name":"Anne Arundel Medical Center","place":["Annapolis, Maryland, United States of America"],"department":["Department of Gastroenterology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nargiz","family":"Muganlinskaya","sequence":"additional","affiliation":[{"name":"Anne Arundel Medical Center","place":["Annapolis, Maryland, United States of America"],"department":["Department of Internal Medicine"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nowreen","family":"Haq","sequence":"additional","affiliation":[{"name":"Anne Arundel Medical Center","place":["Annapolis, Maryland, United States of America"],"department":["Department of Endocrinology"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"issue":"17","key":"pone.0358659.ref001","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1136\/heartjnl-2019-316243","article-title":"Diabetes and coronary artery disease: not just a risk factor","volume":"106","author":"PJ Grant","year":"2020","journal-title":"Heart"},{"issue":"3","key":"pone.0358659.ref002","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1586\/egh.11.23","article-title":"Inflammatory bowel disease: beyond the boundaries of the bowel","volume":"5","author":"GC Actis","year":"2011","journal-title":"Expert Rev Gastroenterol Hepatol"},{"key":"pone.0358659.ref003","doi-asserted-by":"crossref","first-page":"107","DOI":"10.2147\/CEG.S243478","article-title":"Cardiovascular risk in individuals with inflammatory bowel disease","volume":"13","author":"RB Biondi","year":"2020","journal-title":"Clin Exp Gastroenterol"},{"issue":"1","key":"pone.0358659.ref004","first-page":"225","article-title":"The dual GIP and GLP-1 receptor agonist tirzepatide","volume":"20","author":"EZ Fisman","year":"2021","journal-title":"Cardiovasc Diabetol"},{"issue":"19","key":"pone.0358659.ref005","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":"SP Marso","year":"2016","journal-title":"N Engl J Med"},{"key":"pone.0358659.ref006","unstructured":"TriNetX. https:\/\/trinetx.com"},{"issue":"2","key":"pone.0358659.ref007","doi-asserted-by":"crossref","DOI":"10.1093\/jamiaopen\/ooad035","article-title":"A global federated real-world data and analytics platform for research","volume":"6","author":"MB Palchuk","year":"2023","journal-title":"JAMIA Open"},{"issue":"4","key":"pone.0358659.ref008","doi-asserted-by":"crossref","first-page":"444","DOI":"10.4239\/wjd.v5.i4.444","article-title":"Type 2 diabetes and cardiovascular disease","volume":"5","author":"I Mart\u00edn-Tim\u00f3n","year":"2014","journal-title":"World J Diabetes"},{"issue":"2","key":"pone.0358659.ref009","article-title":"Cardiovascular manifestations of inflammatory bowel diseases","volume":"325","author":"Y Xiao","year":"2023","journal-title":"Am J Physiol"},{"key":"pone.0358659.ref010","doi-asserted-by":"crossref","first-page":"2568569","DOI":"10.1155\/2018\/2568569","article-title":"Vascular endothelial dysfunction in inflammatory bowel diseases","author":"AG Gravina","year":"2018","journal-title":"Oxid Med Cell Longev"},{"issue":"4","key":"pone.0358659.ref011","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1056\/NEJMoa1603827","article-title":"Liraglutide and cardiovascular outcomes in type 2 diabetes","volume":"375","author":"SP Marso","year":"2016","journal-title":"N Engl J Med"},{"issue":"3","key":"pone.0358659.ref012","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1111\/dom.13955","article-title":"Semaglutide reduces cardiovascular events in T2D (SUSTAIN and PIONEER","volume":"22","author":"M Husain","year":"2020","journal-title":"). Diabetes Obes Metab"},{"issue":"5","key":"pone.0358659.ref013","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1056\/NEJMoa2410027","article-title":"Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity","volume":"392","author":"M Packer","year":"2025","journal-title":"N Engl J Med"},{"issue":"10","key":"pone.0358659.ref014","article-title":"Long-term risk of arrhythmias in IBD","volume":"20","author":"J Sun","year":"2023","journal-title":"PLoS Med"},{"key":"pone.0358659.ref015","doi-asserted-by":"crossref","first-page":"101218","DOI":"10.1016\/j.ijcha.2023.101218","article-title":"Effects of GLP-1 agonists on mortality and arrhythmias in T2D","volume":"47","author":"MA Al-Sadawi","year":"2023","journal-title":"IJC Heart Vasc"},{"key":"pone.0358659.ref016","unstructured":"Heart Rhythm Society. GLP-1 receptor agonists may reduce atrial fibrillation-related events. https:\/\/www.hrsonline.org\/news\/glp1-study-reduces-afib-events\/"},{"issue":"8","key":"pone.0358659.ref017","first-page":"937","article-title":"GLP-1 receptor agonists and atrial fibrillation prevention in T2D","volume":"8","author":"L Stoll","year":"2023","journal-title":"Basic Transl Sci"},{"key":"pone.0358659.ref018","unstructured":"JAMA Network Open 2025. 2025."},{"issue":"10193","key":"pone.0358659.ref019","first-page":"121","article-title":"Dulaglutide and cardiovascular outcomes in T2D (REWIND","volume":"394","author":"HC Gerstein","year":"2019","journal-title":"). Lancet"},{"key":"pone.0358659.ref020","article-title":"Glucagon-like peptide-1 receptor agonists","volume-title":"StatPearls","author":"L Collins","year":"2024"},{"issue":"6","key":"pone.0358659.ref021","first-page":"857","article-title":"IBD and risk of ischemic heart disease","volume":"7","author":"SL Kristensen","year":"2014","journal-title":"Circ Cardiovasc Qual Outcomes"},{"issue":"9","key":"pone.0358659.ref022","doi-asserted-by":"crossref","DOI":"10.1093\/ecco-jcc\/jjaf167","article-title":"Glucagon-like peptide-1 (GLP-1) receptor agonists in inflammatory bowel disease: mechanisms, clinical implications, and therapeutic potential","volume":"19","author":"M Colwill","year":"2025","journal-title":"J Crohns Colitis"},{"issue":"1","key":"pone.0358659.ref023","first-page":"29","article-title":"IBD and cardiovascular diseases: a concise review","volume":"2","author":"H Wu","year":"2022","journal-title":"Eur Heart J Open"},{"issue":"1","key":"pone.0358659.ref024","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1111\/dom.14203","article-title":"Sodium-glucose co-transporter-2 inhibitors and susceptibility to COVID-19: a population-based retrospective cohort study","volume":"23","author":"C Sainsbury","year":"2021","journal-title":"Diabetes Obes Metab"},{"key":"pone.0358659.ref025","article-title":"Why cochrane should prioritise sharing data","volume":"362","author":"F Shokraneh","year":"2018","journal-title":"BMJ"},{"issue":"4","key":"pone.0358659.ref026","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1111\/dom.13619","article-title":"Largest single-centre experience of dulaglutide for management of diabetes mellitus in solid organ transplant recipients","volume":"21","author":"P Singh","year":"2019","journal-title":"Diabetes Obes Metab"},{"issue":"8","key":"pone.0358659.ref027","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1111\/dom.12929","article-title":"Prevalence of elevated liver enzymes in adults with type 1 diabetes: a multicentre analysis of the German\/Austrian DPV database","volume":"19","author":"M Stadler","year":"2017","journal-title":"Diabetes Obes Metab"},{"issue":"6","key":"pone.0358659.ref028","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1038\/s41574-020-0353-9","article-title":"Endocrine and metabolic link to coronavirus infection","volume":"16","author":"SR Bornstein","year":"2020","journal-title":"Nat Rev Endocrinol"},{"key":"pone.0358659.ref029","article-title":"Glucagon-like receptor agonists and next-generation incretin-based medications: metabolic, cardiovascular, and renal benefits. The","author":"MA Nauck","year":"2026","journal-title":"Lancet"},{"issue":"21","key":"pone.0358659.ref030","article-title":"Antiinflammatory actions of glucagon-like peptide-1-based therapies beyond metabolic benefits","volume":"135","author":"CK Wong","year":"2025","journal-title":"J Clin Invest"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0358659","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T17:32:25Z","timestamp":1790271145000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0358659"}},"subtitle":[],"editor":[{"given":"Marwan Salih","family":"Al-Nimer","sequence":"first","affiliation":[{"name":"University of Diyala College of Medicine","place":["IRAQ"]}],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,9,24]]},"references-count":30,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9,24]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0358659","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,24]]}}}