{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:01:12Z","timestamp":1789084872067,"version":"build-2803163510"},"reference-count":65,"publisher":"Korean Diabetes Association","issue":"1","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["e-dmj.org"],"crossmark-restriction":true},"short-container-title":["Diabetes Metab J"],"published-print":{"date-parts":[[2026,1,1]]},"abstract":"<jats:p>Sodium-glucose cotransporter 2 (SGLT2) inhibitors are established treatments for type 2 diabetes mellitus, heart failure, and chronic kidney disease, with well-documented metabolic and cardiorenal benefits. Emerging evidence indicates that these agents may also exert anticancer effects through mechanisms independent of glucose lowering. Preclinical studies have demonstrated functional SGLT2 expression in tumors such as prostate, pancreatic, breast, colorectal, and bone cancers. Inhibition of SGLT2 decreases tumor glucose uptake, disrupts mitochondrial respiration with subsequent adenosine monophosphate-activated protein kinase activation, and induces endoplasmic reticulum stress and autophagy. Immunomodulatory effects, including programmed death-ligand 1 (PD-L1) degradation and stimulator of interferon genes (STING)\u2013interferon regulatory factor 3 (IRF3)\u2013interferon-\u03b2 (IFN-\u03b2) pathway activation, further illustrate their pleiotropic effects. Observational cohort studies, particularly from nationwide Korean databases, report reduced risks of pancreatic and prostate cancer among new users of SGLT2 inhibitors. In contrast, randomized controlled trials and meta-analyses focused on cardiovascular outcomes demonstrate neutral effects on overall cancer risk, providing reassurance regarding safety. Early translational studies suggest that combining SGLT2 inhibitors with chemotherapy is feasible and tolerable. In this review, we summarize the biological rationale and mechanistic insights underlying the anticancer effects of SGLT2 inhibitors, highlight preclinical and clinical evidence across different cancer types, and discuss challenges and future directions for their integration into oncology.<\/jats:p>","DOI":"10.4093\/dmj.2025.0964","type":"journal-article","created":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T08:49:04Z","timestamp":1767343744000},"page":"1-18","update-policy":"https:\/\/doi.org\/10.4093\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Sodium-Glucose Cotransporter 2 Inhibitors as Emerging Anticancer Agents"],"prefix":"10.4093","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4089-1376","authenticated-orcid":true,"given":"Yun Kyung","family":"Cho","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4043-2396","authenticated-orcid":true,"given":"Chang Hee","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2567","reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-021-00514-z"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.4093\/dmj.2020.0175"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2017.31"},{"key":"ref5","first-page":"S181","volume-title":"9. Pharmacologic approaches to glycemic treatment: standards of care in diabetes-2025","year":"2025"},{"key":"ref6","first-page":"582","volume-title":"2025 Clinical practice guidelines for diabetes management in Korea: recommendation of the Korean Diabetes Association","author":"Kang","year":"2025"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.3390\/cancers17030466"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1511698112"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.728759"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1186\/s11658-024-00599-1"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1590\/s1677-5538.ibju.2018.0271"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines11071867"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-023-05289-w"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1172\/jci154754"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-022-04980-w"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabet.2025.101605"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.4093\/dmj.2024.0693"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2015.12.001"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1097\/cco.0b013e328356da72"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2025.167805"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1507\/endocrj.ej19-0428"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2016.08.014"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23147966"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2020.5120"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2536"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1186\/s40170-019-0203-1"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2024.176803"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2020.113856"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2021.07.035"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1186\/s12935-022-02496-z"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/789174"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2011.01517.x"},{"key":"ref33","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-0273-y"},{"key":"ref34","doi-asserted-by":"publisher","DOI":"10.1007\/s00404-011-2166-5"},{"key":"ref35","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1443045"},{"key":"ref36","doi-asserted-by":"publisher","DOI":"10.1186\/s40170-023-00306-2"},{"key":"ref37","doi-asserted-by":"publisher","DOI":"10.1186\/s40001-025-02749-3"},{"key":"ref38","doi-asserted-by":"publisher","DOI":"10.1021\/acsptsci.0c00144"},{"key":"ref39","doi-asserted-by":"publisher","DOI":"10.3390\/ph18050681"},{"key":"ref40","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaccao.2024.12.004"},{"key":"ref41","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaccao.2024.08.001"},{"key":"ref42","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20205237"},{"key":"ref43","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.31193"},{"key":"ref44","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabet.2025.101698"},{"key":"ref45","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2023.7118"},{"key":"ref46","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-60133-3"},{"key":"ref47","doi-asserted-by":"publisher","DOI":"10.1002\/1878-0261.13508"},{"key":"ref48","doi-asserted-by":"publisher","DOI":"10.1007\/s13340-021-00494-6"},{"key":"ref49","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.16039"},{"key":"ref50","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2020.09.005"},{"key":"ref51","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-022-01221-8"},{"key":"ref52","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-017-4370-8"},{"key":"ref53","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2023.110621"},{"key":"ref54","doi-asserted-by":"publisher","DOI":"10.2337\/db16-0058"},{"key":"ref55","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabet.2024.101571"},{"key":"ref56","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabet.2024.101585"},{"key":"ref57","doi-asserted-by":"publisher","DOI":"10.1186\/s13098-025-01898-z"},{"key":"ref58","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-025-13966-8"},{"key":"ref59","first-page":"159","volume-title":"The cardioprotective and anticancer effects of SGLT2 inhibitors: JACC: cardiooncology state-of-the-art review","author":"Dabour","year":"2024"},{"key":"ref60","doi-asserted-by":"publisher","DOI":"10.1186\/s13098-024-01354-4"},{"key":"ref61","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2022.03.006"},{"key":"ref62","doi-asserted-by":"publisher","DOI":"10.2147\/dddt.s485755"},{"key":"ref63","doi-asserted-by":"publisher","DOI":"10.2337\/dc15-0843"},{"key":"ref64","doi-asserted-by":"publisher","DOI":"10.1136\/bmjdrc-2023-003666"},{"key":"ref65","doi-asserted-by":"publisher","DOI":"10.4093\/dmj.2023.0072"}],"container-title":["Diabetes &amp; Metabolism Journal"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/e-dmj.org\/upload\/pdf\/dmj-2025-0964.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/e-dmj.org\/journal\/view.php?doi=10.4093\/dmj.2025.0964","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/e-dmj.org\/upload\/pdf\/dmj-2025-0964.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T23:34:27Z","timestamp":1768260867000},"score":1,"resource":{"primary":{"URL":"http:\/\/e-dmj.org\/journal\/view.php?doi=10.4093\/dmj.2025.0964"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,1]]},"references-count":65,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"URL":"https:\/\/doi.org\/10.4093\/dmj.2025.0964","relation":{},"ISSN":["2233-6079","2233-6087"],"issn-type":[{"value":"2233-6079","type":"print"},{"value":"2233-6087","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,1]]},"assertion":[{"value":"2025-09-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-01","order":2,"name":"published","label":"Published online","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-01","order":3,"name":"published","label":"Print publication","group":{"name":"publication_history","label":"Publication History"}}]}}