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Preclinical evidence demonstrates functional SGLT2 expression in multiple tumor types and links SGLT2 inhibition to reduced tumor glucose uptake, impaired mitochondrial function, and induction of endoplasmic reticulum stress and autophagy. Additional immunomodulatory effects include PD-L1 degradation and activation of STING–IRF3–IFN-β signaling. Observational studies suggest lower pancreatic and prostate cancer risks, while trials and meta-analyses report neutral overall cancer risk. Translational work supports combination strategies with chemotherapy, and future biomarker-guided patient selection is needed.",{"@graph":69,"@context":123},[70,84,106],{"@type":71,"itemListElement":72},"BreadcrumbList",[73,77,79,82],{"item":74,"name":75,"@type":76,"position":8},"https://docshare.wps.com","Home","ListItem",{"item":78,"name":9,"@type":76,"position":14},"https://docshare.wps.com/document/",{"item":80,"name":35,"@type":76,"position":81},"https://docshare.wps.com/document/healthcare/",3,{"item":83,"name":65,"@type":76,"position":19},"https://docshare.wps.com/document/sodium-glucose-cotransporter-2-inhibitors-as-emerging-anticancer-agents-review/344636/",{"url":83,"name":65,"@type":85,"image":86,"author":91,"headline":65,"publisher":94,"fileFormat":97,"inLanguage":63,"description":67,"dateModified":98,"datePublished":99,"encodingFormat":97,"isAccessibleForFree":100,"interactionStatistic":101},"DigitalDocument",{"url":87,"@type":88,"width":89,"height":90},"https://docshare.wps.com/thumbnails/sodium-glucose-cotransporter-2-inhibitors-as-emerging-anticancer-agents-review/344636.png","ImageObject",300,407,{"name":92,"@type":93},"Logic","Person",{"url":74,"name":95,"@type":96},"DocShare","Organization","application/pdf","2026-11-01","2026-09-22",true,{"@type":102,"interactionType":103,"userInteractionCount":105},"InteractionCounter",{"@type":104},"ViewAction",11,{"@type":107,"mainEntity":108},"FAQPage",[109,115,119],{"name":110,"@type":111,"acceptedAnswer":112},"What anticancer mechanisms are proposed for SGLT2 inhibitors beyond glucose lowering?","Question",{"text":113,"@type":114},"The review describes reduced tumor glucose uptake, mitochondrial dysfunction with AMPK activation, and induction of endoplasmic reticulum stress and autophagy. It also highlights immunomodulation such as PD-L1 degradation and STING–IRF3–IFN-β pathway activation.","Answer",{"name":116,"@type":111,"acceptedAnswer":117},"Which cancer types show functional SGLT2 expression in preclinical studies?",{"text":118,"@type":114},"Preclinical studies cited in the review identify functional SGLT2 expression in tumors including prostate, pancreatic, breast, colorectal, and bone cancers.",{"name":120,"@type":111,"acceptedAnswer":121},"How do randomized trials and observational studies differ regarding cancer risk?",{"text":122,"@type":114},"Observational cohort studies reported reduced risks of pancreatic and prostate cancer among new users. In contrast, randomized controlled trials and meta-analyses focused on cardiovascular outcomes showed neutral effects on overall cancer risk, supporting safety reassurance.","https://schema.org",{"og:url":83,"og:type":125,"og:title":65,"og:site_name":95,"og:description":67},"article",{"robots":127,"canonical":83},"index,follow",{"doc_id":129,"site_id":62},344636,1790098934,{"code":4,"msg":5,"data":132},{"doc_id":129,"user_id":133,"nickname":92,"user_avatar":134,"doc_module":4,"category_id":34,"category_name":35,"doc_title":65,"doc_description":67,"doc_content":135,"file_id":136,"file_url":137,"file_type":138,"file_size":139,"view_count":105,"is_deleted":4,"is_public":8,"is_downloadable":8,"audit_status":8,"page_count":56,"language":140,"language_code":63,"site_id":62,"html_lang":63,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":67,"update_tm":144,"read_time":145},1099513958762,"https://ap-avatar.wpscdn.com/avatar/1000023916a998db790?x-image-process=image/resize,m_fixed,w_180,h_180&k=1784791008015729253","DIABETES & METABOLISM JOURNAL  \nSodium-Glucose Cotransporter 2 Inhibitors as Emerging Anticancer Agents  \nYun Kyung Cho, Chang Hee Jung  \nDiabetes MetabJ 2026;50:1-18 | [https://doi.org/10.4093/dmj.2025.0964](https://doi.org/10.4093/dmj.2025.0964)  \nHighlights  \n• SGLT2 inhibitors emerge as promising anticancer drug candidates.  \n• SGLT2 inhibition decreases tumor glucose uptake and disrupts mitochondrial function in cancer cells.  \n• These agents also enhance antitumor immunity by promoting PD-L1 degradation.  \n• Observational studies suggest reduced risks of pancreatic and prostate cancers.  \n• Future strategies for biomarker-guided patient selection and monitoring are needed.  \nHow to cite this article:  \nCho YK, Jung CH. Sodium–Glucose Cotransporter 2 Inhibitors as Emerging Anticancer Agents. Diabetes Metab J. Diabetes Metab J 2026;50:1-18. [https://doi.org/10.4093/dmj.2025.0964](https://doi.org/10.4093/dmj.2025.0964)  \nReview  \nPharmacotherapy  \nDiabetes Metab J 2026;50:1-18 [https://doi.org/10.4093/dmj.2025.0964](https://doi.org/10.4093/dmj.2025.0964)[ ](https://doi.org/10.4093/dmj.2025.0964)pISSN 2233-6079 · eISSN 2233-6087  \nDIABETES & METABOLISM JOURNAL  \nSodium-Glucose Cotransporter 2 Inhibitors as Emerging Anticancer Agents  \nYun Kyung Cho, Chang Hee Jung  \nDepartment of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea  \nSodium-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)–interferon regulatory factor 3 (IRF3)– interferon-β (IFN-β) 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.  \nKeywords: Antineoplastic agents; Neoplasms; Sodium-glucose transporter 2 inhibitors  \nINTRODUCTION  \nCancer is the leading cause of death worldwide, with 19.3 million new cases and 10 million deaths reported in 2020, and the burden is expected to rise in coming decades [1,2]. In Korea, cancer is also the foremost cause of mortality, particularly among individuals with diabetes mellitus, who face higher risks of both cancer incidence and mortality [3]. Despite progress in precision medicine and targeted therapies, development of new anticancer agents remains time-and resource-intensive, requiring approximately 10 years and 2.6 billion US dollars for a single drug to reach clinical application [4] . These challenges underscore the importance of alternative strategies such as drug repurposing, which leverages the known safety  \nand pharmacology of existing therapies to accele","cbCainQ2zAhKTANl","https://ap.wps.com/l/cbCainQ2zAhKTANl","pdf",2161873,"English","# Highlights\n# Review\n## Pharmacotherapy\n## Introduction","[{\"question\":\"What anticancer mechanisms are proposed for SGLT2 inhibitors beyond glucose lowering?\",\"answer\":\"The review describes reduced tumor glucose uptake, mitochondrial dysfunction with AMPK activation, and induction of endoplasmic reticulum stress and autophagy. It also highlights immunomodulation such as PD-L1 degradation and STING–IRF3–IFN-β pathway activation.\"},{\"question\":\"Which cancer types show functional SGLT2 expression in preclinical studies?\",\"answer\":\"Preclinical studies cited in the review identify functional SGLT2 expression in tumors including prostate, pancreatic, breast, colorectal, and bone cancers.\"},{\"question\":\"How do randomized trials and observational studies differ regarding cancer risk?\",\"answer\":\"Observational cohort studies reported reduced risks of pancreatic and prostate cancer among new users. In contrast, randomized controlled trials and meta-analyses focused on cardiovascular outcomes showed neutral effects on overall cancer risk, supporting safety reassurance.\"}]","Sodium-Glucose Cotransporter 2 Inhibitors as Emerging Anticancer Agents - Review | PDF",1790054716,48]