{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T13:43:11Z","timestamp":1790602991552,"version":"4.1.0"},"reference-count":37,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T00:00:00Z","timestamp":1766707200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Investigative Medicine"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:p>\n                    Peripheral artery disease (PAD) is associated with a high risk of cardiovascular events. While glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated cardiovascular benefit in patients with diabetes, their role in patients with PAD without diabetes is not well understood. This study aimed to assess the impact of GLP-1RA therapy on cardiovascular outcomes in nondiabetic PAD patients. We conducted a retrospective cohort study using the TriNetX U.S. collaborative network, identifying adults aged 18\u201389 with PAD and no history of diabetes from January 2014 to January 2024. Patients treated with GLP-1RAs were compared with untreated counterparts. A 1:1 greedy nearest neighbor propensity score matching was performed to balance baseline characteristics. The primary outcomes were 3-point major adverse cardiovascular events (MACE) defined as nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death, all-cause mortality; major adverse limb events (MALE) defined as limb-threatening ischemia, revascularization procedures, or major amputation. Cox regression and Kaplan\u2013Meier analysis were used to assess outcomes over a 5-year follow-up period. After matching, 13,555 patients remained in each group with well-balanced covariates. GLP-1RA use was associated with lower risk of MACE (hazard ratio (HR): 0.61; 95% confidence interval (CI): 0.57\u20130.66;\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009&lt;\u20090.001), all-cause mortality (HR: 0.40; 95% CI: 0.35\u20130.46;\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009&lt;\u20090.001), and MALE (HR: 0.22; 95% CI: 0.17\u20130.28;\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009&lt;\u20090.001). In a sensitivity analysis focusing on semaglutide use initiated post-2021, the benefits remained robust for both MACE (HR: 0.55; 95% CI: 0.50\u20130.60) and all-cause mortality (HR: 0.303; 95% CI: 0.25\u20130.36). In this large real-world cohort, GLP-1RA therapy was associated with significantly reduced cardiovascular and limb-related events in nondiabetic patients with PAD. These findings support the potential role of GLP-1RAs in cardiovascular risk reduction beyond diabetes and highlight the need for prospective randomized trials in this population.\n                  <\/jats:p>","DOI":"10.1177\/10815589251393978","type":"journal-article","created":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T04:05:31Z","timestamp":1761365131000},"page":"641-653","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["Impact of GLP-1 receptor agonists on cardiovascular outcomes in patients with peripheral artery disease without diabetes: A propensity score-matched analysis"],"prefix":"10.1177","volume":"74","author":[{"given":"Emmanuel","family":"Daniel","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Trinity Health Ann Arbor, Ypsilanti, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"El-Nayir","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Trinity Health Ann Arbor, Ypsilanti, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kayode","family":"Ogunniyi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Richmond University Medical Center, Mount Sinai, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yash","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Trinity Health Ann Arbor, Ypsilanti, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Olayiwola","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Saint Peter\u2019s University Hospital, New Brunswick, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omotola","family":"Oredipe","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Cook County Health, Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Nwankwo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, CityHealth Specialist Hospital, Abakaliki, Nigeria"},{"name":"Department of Internal Medicine, Suny Upstate Medical University Hospital, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karldon","family":"Nwaezeapu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Trinity Health Ann Arbor, Ypsilanti, MI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tioluwani","family":"Ojo","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, CityHealth Specialist Hospital, Abakaliki, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,12,26]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000001153"},{"key":"e_1_3_3_3_2","doi-asserted-by":"crossref","unstructured":"Eid MA Mehta K Barnes JA et al. The global burden of peripheral artery disease. J Vasc Surg 2023; 77(4): 1119\u20131126.e1.","DOI":"10.1016\/j.jvs.2022.12.015"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.121.318535"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.119.312142"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.033886"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMp1001578"},{"key":"e_1_3_3_8_2","unstructured":"Pillai P and Modarressi T. GLP1RAs in clinical practice: therapeutic advances and safety perspectives. American College of Cardiology Expert Analysis https:\/\/www.acc.org\/Latest-in-Cardiology\/Articles\/2024\/04\/15\/11\/19\/http%3a%2f%2fwww.acc.org%2fLatest-in-Cardiology%2fArticles%2f2024%2f04%2f15%2f11%2f19%2fGLP1RAs-in-Clinical-Practice (accessed 20 January 2025)."},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2307563"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/jamiaopen\/ooad035"},{"key":"e_1_3_3_11_2","unstructured":"Datasets & Analytics. TriNetX https:\/\/trinetx.com\/data-sets-analytics\/code.pdf."},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.705"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(21)00203-5"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1603827"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.118.034516"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1607141"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199202063260605"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2261-5-14"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.19574"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.7326\/ANNALS-24-01590"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)01498-3"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1111\/dom.15869"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2024.1545"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2007.03.054"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdiacomp.2022.108390"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2206038"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/srep10202"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-019-0954-6"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.289.14.1799"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2016.02.005"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-13-0414"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2022.04.004"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.2337\/db15-1141"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.5966\/sctm.2012-0064"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.113.301217"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1709118"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2000052"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehae179"}],"container-title":["Journal of Investigative Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/10815589251393978","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/10815589251393978","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/10815589251393978","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T11:08:43Z","timestamp":1788174523000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/10815589251393978"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,26]]},"references-count":37,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1177\/10815589251393978"],"URL":"https:\/\/doi.org\/10.1177\/10815589251393978","relation":{},"ISSN":["1081-5589","1708-8267"],"issn-type":[{"value":"1081-5589","type":"print"},{"value":"1708-8267","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,26]]}}}