{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:17:50Z","timestamp":1790810270732,"version":"4.1.0"},"reference-count":73,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Incubation Competence Centre of the Centre of Excellence for Interdisciplinary Research, Development and Innovation of the University of Szeged","award":["SZTE_SZAOK-KKA_SZAOK-SZBK-2023\/5S809"],"award-info":[{"award-number":["SZTE_SZAOK-KKA_SZAOK-SZBK-2023\/5S809"]}]},{"award":["SZTE_SZAOK-KKA_SZAOK-SZBK-2023\/5S809"],"award-info":[{"award-number":["SZTE_SZAOK-KKA_SZAOK-SZBK-2023\/5S809"]}],"id":[{"id":"https:\/\/ror.org\/01pnej532","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Type 2 diabetes mellitus (T2DM) is a progressive metabolic disease that necessitates individualized therapeutic strategies focusing on both glycemic control and the mitigation of comorbidities. In recent years, sodium-glucose cotransporter-2 (SGLT2) inhibitors have emerged as a cornerstone of modern treatment due to their unique renal mechanism of action. This review summarizes the metabolic mechanisms, pleiotropic effects, and clinical significance of SGLT2 inhibitors in the management of T2DM. This review provides an updated overview of the metabolic and systemic effects of SGLT2 inhibition. By promoting glycosuria, SGLT2 inhibitors induce a negative energy balance that contributes to modest weight loss, improved body composition, and beneficial alterations in lipid metabolism. Beyond their metabolic effects, accumulating preclinical evidence suggests that SGLT2 inhibitors exert anti-inflammatory and antifibrotic actions, partly through modulation of macrophage polarization and attenuation of oxidative stress. The clinical utility of SGLT2 inhibitors is highlighted through the review of major cardiovascular and renal outcome trials, which confirm significant benefits in reducing heart failure hospitalizations and slowing the progression of chronic kidney disease. Finally, we integrate these findings into the context of the latest international guidelines while addressing safety profiles, the rationale for combination therapies, and the transition toward a personalized, risk-based management approach in T2DM.<\/jats:p>","DOI":"10.3390\/antiox15050553","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T09:46:11Z","timestamp":1777455971000},"page":"553","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Sodium-Glucose Cotransporter-2 Inhibitors in Type 2 Diabetes: From Metabolic Mechanisms to International Guidelines"],"prefix":"10.3390","volume":"15","author":[{"given":"Tam\u00e1s","family":"V\u00e1rkonyi","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, 6703 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krisztina","family":"Kupai","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, 6703 Szeged, Hungary"},{"name":"Department of Oral Biology and Experimental Dental Research, Faculty of Dentistry, University of Szeged, 6703 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsu Lin","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Oral Biology and Experimental Dental Research, Faculty of Dentistry, University of Szeged, 6703 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danica","family":"Matusovits-Varga","sequence":"additional","affiliation":[{"name":"Department of Oral Biology and Experimental Dental Research, Faculty of Dentistry, University of Szeged, 6703 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5818-4557","authenticated-orcid":false,"given":"D\u00e1niel","family":"Priksz","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Pharmacotherapy, Faculty of Medicine, Univerity of Debrecen, 4006 Debrecen, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1kos","family":"V\u00e1rkonyi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, 6703 Szeged, Hungary"},{"name":"Department of Oral Biology and Experimental Dental Research, Faculty of Dentistry, University of Szeged, 6703 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Csaba","family":"Lengyel","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, 6703 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anik\u00f3","family":"P\u00f3sa","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, 6703 Szeged, Hungary"},{"name":"Department of Oral Biology and Experimental Dental Research, Faculty of Dentistry, University of Szeged, 6703 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1111\/1753-0407.12524","article-title":"American Diabetes Association Standards of Medical Care in Diabetes 2017","volume":"9","author":"Marathe","year":"2017","journal-title":"J. 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