{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T10:05:26Z","timestamp":1785492326006,"version":"3.56.0"},"reference-count":153,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T00:00:00Z","timestamp":1757376000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Contemporary diabetes management is progressively moving away from a glucocentric approach, with growing expectations that novel antidiabetic agents offer benefits beyond glycaemic control. Sodium\u2013glucose cotransporter 2 inhibitors (SGLT2i) have emerged as a cornerstone in the treatment of type 2 diabetes mellitus (T2DM). In addition to reducing blood glucose levels by promoting renal glucose excretion, these agents contribute significantly to cardio\u2013renal\u2013metabolic protection and are associated with improved cardiovascular outcomes and prolonged survival. Although SGLT2 inhibitors do not exhibit a class effect in all clinical aspects, growing evidence suggests their potential in a variety of additional therapeutic areas. We conducted an in-depth review of current scientific literature and clinical studies regarding this class of drugs. SGLT2 inhibitors demonstrate neuroprotective properties and may provide benefits in neurodegenerative disorders such as Alzheimer\u2019s and Parkinson\u2019s disease, potentially through the improvement of mitochondrial function and attenuation of inflammatory responses. Their anti-inflammatory and antioxidative effects are closely linked to reductions in cardiac and renal fibrosis. Other observed benefits include weight loss, improved insulin sensitivity, normalization of serum uric acid, and a reduction in hepatic steatosis\u2014each with important metabolic implications. Furthermore, SGLT2 inhibitors have been shown to positively influence iron metabolism and improve erythrocyte indices. Emerging data also indicate beneficial effects in women with polycystic ovary syndrome. Another promising area of investigation involves the modulation of Klotho protein expression and support of vascular homeostasis. In oncology, SGLT2 inhibitors are gaining attention, with encouraging preclinical results observed in malignancies such as pancreatic, thyroid, breast, and lung cancers. Based on a comprehensive evaluation of the existing body of evidence, it is anticipated that the clinical indications for SGLT2 inhibitors will expand beyond the cardio\u2013renal\u2013metabolic axis in the near future.<\/jats:p>","DOI":"10.3390\/jcm14186348","type":"journal-article","created":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T08:43:54Z","timestamp":1757493834000},"page":"6348","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Beyond the Cardio\u2013Renal\u2013Metabolic Axis: Emerging Therapeutic Targets and Novel Mechanisms of Action of Flozins"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8279-0373","authenticated-orcid":false,"given":"Wojciech","family":"Matuszewski","sequence":"first","affiliation":[{"name":"Clinic of Endocrinology, Diabetology and Internal Medicine, School of Medicine, Collegium Medicum, University of Warmia and Mazury, 10-082 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0842-285X","authenticated-orcid":false,"given":"Lena","family":"Tomaszek","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, School of Medicine, Collegium Medicum, University of Warmia and Mazury, 10-082 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micha\u0142","family":"Szklarz","sequence":"additional","affiliation":[{"name":"Clinic of Endocrinology, Diabetology and Internal Medicine, School of Medicine, Collegium Medicum, University of Warmia and Mazury, 10-082 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8167-6658","authenticated-orcid":false,"given":"Jan Marek","family":"G\u00f3rny","sequence":"additional","affiliation":[{"name":"Clinic of Endocrinology, Diabetology and Internal Medicine, School of Medicine, Collegium Medicum, University of Warmia and Mazury, 10-082 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7590-5790","authenticated-orcid":false,"given":"Bernard","family":"Kordas","sequence":"additional","affiliation":[{"name":"Department of Human Physiology and Pathophysiology, University of Warmia and Mazury, 10-082 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Rutkowska","sequence":"additional","affiliation":[{"name":"Clinic of Endocrinology, Diabetology and Internal Medicine, School of Medicine, Collegium Medicum, University of Warmia and Mazury, 10-082 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8665-6606","authenticated-orcid":false,"given":"Judyta","family":"Juranek","sequence":"additional","affiliation":[{"name":"Department of Human Physiology and Pathophysiology, University of Warmia and Mazury, 10-082 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e143","DOI":"10.1038\/nutd.2014.40","article-title":"Efficacy, safety and regulatory status of SGLT2 inhibitors: Focus on canagliflozin","volume":"4","author":"Haas","year":"2014","journal-title":"Nutr. 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