{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T20:44:59Z","timestamp":1792701899286,"version":"4.5.0"},"reference-count":348,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T00:00:00Z","timestamp":1732060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Diabetes mellitus (DM) is a significant risk factor for various cancers, with the impact of anti-diabetic therapies on cancer progression differing across malignancies. Among these therapies, metformin has gained attention for its potential anti-cancer effects, primarily through modulation of the AMP-activated protein kinase\/mammalian target of rapamycin (AMPK\/mTOR) pathway and the induction of autophagy. Beyond metformin, other conventional anti-diabetic treatments, such as insulin, sulfonylureas (SUs), pioglitazone, and dipeptidyl peptidase-4 (DPP-4) inhibitors, have also been examined for their roles in cancer biology, though findings are often inconclusive. More recently, novel medications, like glucagon-like peptide-1 (GLP-1) receptor agonists, dual GLP-1\/glucose-dependent insulinotropic polypeptide (GIP) agonists, and sodium-glucose co-transporter-2 (SGLT-2) inhibitors, have revolutionized DM management by not only improving glycemic control but also delivering substantial cardiovascular and renal benefits. Given their diverse metabolic effects, including anti-obesogenic properties, these novel agents are now under meticulous investigation for their potential influence on tumorigenesis and cancer advancement. This review aims to offer a comprehensive exploration of the evolving landscape of glucose-lowering treatments and their implications in cancer biology. It critically evaluates experimental evidence surrounding the molecular mechanisms by which these medications may modulate oncogenic signaling pathways and reshape the tumor microenvironment (TME). Furthermore, it assesses translational research and clinical trials to gauge the practical relevance of these findings in real-world settings. Finally, it explores the potential of anti-diabetic medications as adjuncts in cancer treatment, particularly in enhancing the efficacy of chemotherapy, minimizing toxicity, and addressing resistance within the framework of immunotherapy.<\/jats:p>","DOI":"10.3390\/biom14111479","type":"journal-article","created":{"date-parts":[[2024,11,21]],"date-time":"2024-11-21T04:46:11Z","timestamp":1732164371000},"page":"1479","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Anti-Diabetic Therapies and Cancer: From Bench to Bedside"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4338-4879","authenticated-orcid":false,"given":"Dimitris","family":"Kounatidis","sequence":"first","affiliation":[{"name":"Diabetes Center, First Department of Propaedeutic Internal Medicine, Medical School, Laiko General Hospital, National and Kapustina University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3874-5393","authenticated-orcid":false,"given":"Natalia G.","family":"Vallianou","sequence":"additional","affiliation":[{"name":"First Department of Internal Medicine, Sismanogleio General Hospital, 15126 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6912-4042","authenticated-orcid":false,"given":"Irene","family":"Karampela","sequence":"additional","affiliation":[{"name":"2nd Department of Critical Care, Medical School, Attikon General University Hospital, University of Athens, 1 Rimini str., 12461 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni","family":"Rebelos","sequence":"additional","affiliation":[{"name":"Diabetes Center, First Department of Propaedeutic Internal Medicine, Medical School, Laiko General Hospital, National and Kapustina University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Kouveletsou","sequence":"additional","affiliation":[{"name":"Diabetes Center, First Department of Propaedeutic Internal Medicine, Medical School, Laiko General Hospital, National and Kapustina University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasileios","family":"Dalopoulos","sequence":"additional","affiliation":[{"name":"First Department of Internal Medicine, Sismanogleio General Hospital, 15126 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petros","family":"Koufopoulos","sequence":"additional","affiliation":[{"name":"First Department of Internal Medicine, Sismanogleio General Hospital, 15126 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evanthia","family":"Diakoumopoulou","sequence":"additional","affiliation":[{"name":"Diabetes Center, First Department of Propaedeutic Internal Medicine, Medical School, Laiko General Hospital, National and Kapustina University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0615-2534","authenticated-orcid":false,"given":"Nikolaos","family":"Tentolouris","sequence":"additional","affiliation":[{"name":"Diabetes Center, First Department of Propaedeutic Internal Medicine, Medical School, Laiko General Hospital, National and Kapustina University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7008-388X","authenticated-orcid":false,"given":"Maria","family":"Dalamaga","sequence":"additional","affiliation":[{"name":"Department of Biological Chemistry, National and Kapodistrian University of Athens, 75 Mikras Asias str., 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e2004","DOI":"10.1002\/hsr2.2004","article-title":"Diabetes mellitus, the fastest growing global public health concern: Early detection should be focused","volume":"7","author":"Hossain","year":"2024","journal-title":"Health Sci. 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