{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:55:22Z","timestamp":1791474922198,"version":"4.3.4"},"reference-count":13,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Tirzepatide is a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist used in patients with type 2 diabetes and obesity. Although tirzepatide improves metabolic and cardiovascular risk factors, its association with venous thromboembolism, including pulmonary embolism and deep vein thrombosis, remains insufficiently characterized in real-world populations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a population-based retrospective cohort study using the TriNetX US Collaborative Network. Adults with type 2 diabetes and overweight or obesity who initiated tirzepatide were propensity score matched to patients receiving lifestyle intervention alone with no exposure to weight-loss medications. Outcomes included incident pulmonary embolism, deep vein thrombosis, and superficial vein thrombosis occurring between 30 days and 12 months after index. Additional analyses included a 90-day landmark sensitivity analysis and an active comparator analysis comparing tirzepatide with semaglutide.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      After propensity score matching for demographic, metabolic, and clinical covariates, 235, 200 patients were included in the primary analysis (117, 600 per cohort). Tirzepatide use was associated with a significantly lower 12-month risk of pulmonary embolism compared with lifestyle intervention alone (RR, 0.215; 95% CI, 0.185\u20130.250; HR, 0.258; 95% CI, 0.222\u20130.299; log-rank\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.001). Similar reductions were observed for deep vein thrombosis (RR, 0.303; 95% CI, 0.270\u20130.340; HR, 0.361; 95% CI, 0.322\u20130.406; log-rank\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.001). No statistically significant difference was observed for superficial vein thrombosis (RR, 0.716; 95% CI, 0.484\u20131.060; HR, 0.868; 95% CI, 0.586\u20131.286; log-rank P\u00a0=\u00a00.480). Findings for pulmonary embolism and deep vein thrombosis remained significant in the 90-day landmark analysis. In the semaglutide comparator analysis, tirzepatide was associated with a significantly lower risk of deep vein thrombosis, while the pulmonary embolism association was significant by risk-ratio analysis but not by Cox regression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In this large multicenter cohort study, tirzepatide use was associated with a lower risk of pulmonary embolism and deep vein thrombosis compared with lifestyle intervention alone. These findings suggest a potential association between tirzepatide use and lower observed rates of thromboembolic events in patients with diabetes and obesity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1885961","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T04:41:40Z","timestamp":1782880900000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Tirzepatide and reduced risk of pulmonary embolism and deep vein thrombosis: a multicenter U.S. cohort study"],"prefix":"10.3389","volume":"17","author":[{"given":"Fredy","family":"Kahkedjian","sequence":"first","affiliation":[{"name":"Faculty of Medicine, American University of Beirut","place":["Beirut, Lebanon"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaffer","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Weill Cornell Medicine","place":["New York, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Firas","family":"Kreidieh","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Hematology-Oncology, American University of Beirut Medical Center","place":["Beirut, Lebanon"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.115.306841","article-title":"Global burden of thrombosis: Epidemiologic aspects","volume":"118","author":"Wendelboe","year":"2016","journal-title":"Circ Res"},{"key":"B2","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1186\/s12933-021-01372-w","article-title":"Hypofibrinolysis in type 2 diabetes and its clinical implications: From mechanisms to pharmacological modulation","volume":"20","author":"Bryk-Wi\u0105zania","year":"2021","journal-title":"Cardiovasc Diabetol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3390\/ph14100991","article-title":"Efficacy and safety of tirzepatide in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of randomized phase II\/III trials","volume":"14","author":"Bhagavathula","year":"2021","journal-title":"Pharm (Basel)"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2025015871","article-title":"Glucagon-like peptide 1 receptor agonists and venous thromboembolism in type 2 diabetes: A target trial emulation","volume":"9","author":"Chiang","year":"2025","journal-title":"Blood Adv"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.aed.2026.02.005","article-title":"A heavy price for lightness: Pulmonary embolism following tirzepatide initiation","author":"Aleem","year":"2026","journal-title":"AACE Endocrinol 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Elm","year":"2007","journal-title":"Bmj"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3390\/ijms262110292","article-title":"The interplay between obesity and venous thromboembolism: From molecular aspects to clinical issue","volume":"26","author":"Zawadzka","year":"2025","journal-title":"Int J Mol Sci"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2206038","article-title":"Tirzepatide once weekly for the treatment of obesity","volume":"387","author":"Jastreboff","year":"2022","journal-title":"N Engl J Med"},{"key":"B11","doi-asserted-by":"publisher","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":"B12","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa2404881","article-title":"Tirzepatide for the treatment of obstructive sleep apnea and obesity","volume":"391","author":"Malhotra","year":"2024","journal-title":"N Engl J Med"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/jvd3010001","article-title":"Factors associated with the evolution of superficial vein thrombosis and its impact on the quality of life: Results from a prospective, unicentric study","volume":"3","author":"Ros G\u00f3mez","year":"2024","journal-title":"J Vasc Dis"}],"container-title":["Frontiers in 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