{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T06:02:20Z","timestamp":1790229740704,"version":"4.1.0"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"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. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Diabetic foot complications affect up to 25% of patients with type 2 diabetes (T2D) and represent a major cause of morbidity. The dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist - tirzepatide (TZP) has demonstrated superior glycemic control compared with semaglutide however, evidence regarding its effects on diabetic foot complications (DFCs) remains limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a retrospective cohort study using the TriNetX network. Adults with T2D initiating TZP, sulfonylurea (SU), dipeptidyl peptidase-4 inhibitors (DPP-4is), sodium\u2013glucose cotransporter-2 inhibitors (SGLT2is), and glucagon-like peptide-1 receptor agonists (GLP-1RAs) between January 2022 and July 2025 were included. Propensity score matching created balanced cohorts for four comparisons. The primary outcome was the risk of DFC - a composite of ulcers, infections, critical limb ischemia, and revascularization or amputation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>After matching, four cohorts included 141,002 patients per arm (TZP vs. SU), 131,449 patients per arm (TZP vs. DPP-4i), 146,321 patients per arm (TZP vs. SGLT2i), and 97,457 patients per arm (TZP vs. GLP-1RA). Compared with SU, TZP was associated with reduced diabetic foot complications (HR, 0.80; 95% CI, 0.76\u20130.84). Similar reductions were observed versus DPP-4i (HR, 0.83; 95% CI, 0.78\u20130.87) and SGLT2i (HR, 0.88; 95% CI, 0.83\u20130.92). No difference was found versus GLP-1RA (HR, 0.97; 95% CI, 0.91\u20131.03).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>TZP was associated with a reduction in diabetic foot complications compared with SU, DPP-4i, and SGLT2i, with outcomes similar to GLP-1RA. These findings suggest tirzepatide may be a valuable option for patients at risk of ulceration or amputation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1880132","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T05:37:45Z","timestamp":1790228265000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Tirzepatide versus other anti-diabetic agents for the prevention of diabetic foot complications in patients with type 2 diabetes"],"prefix":"10.3389","volume":"17","author":[{"given":"Chia-Yu","family":"Kuo","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Chi Mei Medical Center","place":["Tainan, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jheng-Yan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Chi Mei Medical Center","place":["Tainan, Taiwan"]},{"name":"Department of Public Health, College of Medicine, National Cheng Kung University","place":["Tainan, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya-Wen","family":"Tsai","sequence":"additional","affiliation":[{"name":"Division of Preventive Medicine, Chi Mei Medical Center","place":["Tainan, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Cheng","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Medicine, Chi Mei Medical Center","place":["Tainan, Taiwan"]},{"name":"School of Medicine, College of Medicine, National Sun Yat-sen University","place":["Kaohsiung, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiun-Ling","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University","place":["Tainan, Taiwan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2367","DOI":"10.1056\/NEJMra1615439","article-title":"Diabetic foot ulcers and their recurrence","volume":"376","author":"Armstrong","year":"2017","journal-title":"N. 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