{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:59:06Z","timestamp":1790744346411,"version":"4.1.0"},"reference-count":93,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T00:00:00Z","timestamp":1751414400000},"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:p>The prevalence of diabetes mellitus is increasing and is linked to several complications, including diabetic foot. Novel glucose-lowering agents are sought that also have beneficial effects in reducing diabetic complications. Among the novel glucose-lowering agents demonstrating clinical promise, three classes stand out: dipeptidyl peptidase-4 inhibitors (DPP-4is), glucagon-like peptide-1 receptor agonists (GLP-1RAs), and sodium-glucose cotransporter-2 inhibitors (SGLT2is). Some of these agents provide cardiovascular and kidney benefits, and there is evidence suggesting they also offer protective effects against diabetic foot complications. In this review, we summarize the preclinical and clinical evidence proof these three glucose-lowering agents for diabetic foot, highlighting their potential in enhancing diabetic wound healing and limb preservation. In conclusion, existing available trials have shown that certain DPP-4is and GLP-1RAs possess protective effects against diabetic foot conditions. However, SGLT2is have not demonstrated a significant protective effect. We encourage larger-scale studies on the protective effects of these three types of drugs for diabetic foot to guide physicians in providing personalized treatment strategies, achieving blood glucose targets, and promoting the healing of chronic wounds in patients.<\/jats:p>","DOI":"10.3389\/fendo.2025.1581403","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T04:14:26Z","timestamp":1751429666000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Novel glucose-lowering agents that benefit diabetic foot: icing on the cake"],"prefix":"10.3389","volume":"16","author":[{"given":"Qin","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyan","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunli","family":"Rui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobu","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David G.","family":"Armstrong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wuquan","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2018.02.023","article-title":"IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045","volume":"138","author":"Cho","year":"2018","journal-title":"Diabetes Res Clin Pract"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.2337\/dci22-0043","article-title":"Etiology, epidemiology, and disparities in the burden of diabetic foot ulcers","volume":"46","author":"McDermott","year":"2023","journal-title":"Diabetes Care"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.reth.2025.02.005","article-title":"Platelet concentrates in diabetic foot ulcers: A comparative review of PRP, PRF, and CGF with case insights","volume":"28","author":"Yang","year":"2025","journal-title":"Regener Ther"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1615439","article-title":"Diabetic foot ulcers and their recurrence","volume":"376","author":"Armstrong","year":"2017","journal-title":"N Engl J Med"},{"key":"B5","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/s13047-020-00383-2","article-title":"Five year mortality and direct costs of care for people with diabetic foot complications are comparable to cancer","volume":"13","author":"Armstrong","year":"2020","journal-title":"J Foot Ankle Res"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1177\/2050312120987385","article-title":"Prevalence and associated factors of diabetic foot ulcers among type 2 diabetic patients attending chronic follow-up clinics at governmental hospitals of Harari Region, Eastern Ethiopia: A 5-year (2013-2017) retrospective study","volume":"9","author":"Tola","year":"2021","journal-title":"SAGE Open Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jconrel.2024.06.050","article-title":"Exosomal miRNA-26b-5p from PRP suppresses NETs by targeting MMP-8 to promote diabetic wound healing","volume":"372","author":"Rui","year":"2024","journal-title":"J Control Release"},{"key":"B8","doi-asserted-by":"publisher","first-page":"37","DOI":"10.4239\/wjd.v6.i1.37","article-title":"Literature review on the management of diabetic foot ulcer","volume":"6","author":"Yazdanpanah","year":"2015","journal-title":"World J Diabetes"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1093\/burnst\/tkad003","article-title":"Sphingosine-1-phosphate derived from PRP-Exos promotes angiogenesis in diabetic wound healing via the S1PR1\/AKT\/FN1 signalling pathway","volume":"11","author":"Chen","year":"2023","journal-title":"Burns Trauma"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1177\/15347346221097283","article-title":"Major amputation in non-healing ulcers: outcomes and economic issues. 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