{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T19:39:47Z","timestamp":1790797187672,"version":"4.1.0"},"reference-count":120,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T00:00:00Z","timestamp":1753660800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: Chronic Kidney Disease (CKD) is a major global health issue, with diabetes being its primary cause and cardiovascular disease contributing significantly to patient mortality. Recently, two classes of medications\u2014sodium\u2013glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs)\u2014have shown promise in protecting both kidney and heart health beyond their effects on blood sugar control. Methods: We conducted a narrative review summarizing the findings of different clinical trials and mechanistic studies evaluating the effect of SGLT2i and GLP-1 RAs on kidney function, cardiovascular outcomes, and overall disease progression in patients with CKD and DKD. Results: SGLT2i significantly mitigate kidney injury by restoring tubuloglomerular feedback, reducing intraglomerular hypertension, and attenuating inflammation, fibrosis, and oxidative stress. GLP-1 RAs complement these effects by enhancing endothelial function, promoting weight and blood pressure control, and exerting direct anti-inflammatory and anti-fibrotic actions on renal tissues. Landmark trials\u2014CREDENCE, DAPA-CKD, and EMPA-KIDNEY\u2014demonstrate that SGLT2i reduce the risk of kidney failure and renal or cardiovascular death by 25\u201340% in both diabetic and non-diabetic CKD populations. Likewise, trials such as LEADER, SUSTAIN, and AWARD-7 confirm that GLP-1 RAs slow renal function decline and improve cardiovascular outcomes. Early evidence suggests that using both drugs together may offer even greater benefits through multiple mechanisms. Conclusions: SGLT2i and GLP-1 RAs have redefined the therapeutic landscape of CKD by offering organ-protective benefits that extend beyond glycemic control. Whether used individually or in combination, these agents represent a paradigm shift toward integrated cardiorenal-metabolic care. A deeper understanding of their mechanisms and clinical utility in both diabetic and non-diabetic populations can inform evidence-based strategies to slow disease progression, reduce cardiovascular risk, and improve long-term patient outcomes in CKD.<\/jats:p>","DOI":"10.3390\/ph18081130","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T14:50:03Z","timestamp":1753714203000},"page":"1130","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Repurposing Diabetes Therapies in CKD: Mechanistic Insights, Clinical Outcomes and Safety of SGLT2i and GLP-1 RAs"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8454-8158","authenticated-orcid":false,"given":"Syed Arman","family":"Rabbani","sequence":"first","affiliation":[{"name":"RAK College of Pharmacy, RAK Medical and Health Sciences University, Ras Al Khaimah 11172, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"El-Tanani","sequence":"additional","affiliation":[{"name":"RAK College of Pharmacy, RAK Medical and Health Sciences University, Ras Al Khaimah 11172, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rakesh","family":"Kumar","sequence":"additional","affiliation":[{"name":"Amity Institute of Pharmacy, Amity University, Gurgaon 122413, Haryana, India"},{"name":"Department of Pharmacy, Jagannath University, Bahadurgarh 124507, Haryana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manita","family":"Saini","sequence":"additional","affiliation":[{"name":"Amity Institute of Pharmacy, Amity University, Gurgaon 122413, Haryana, India"},{"name":"Geeta Institute of Pharmacy, Geeta University, Panipat 132145, Haryana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yahia","family":"El-Tanani","sequence":"additional","affiliation":[{"name":"Royal Cornwall Hospital, NHS Trust, Truro TR1 3LJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shrestha","family":"Sharma","sequence":"additional","affiliation":[{"name":"Amity Institute of Pharmacy, Amity University, Gurgaon 122413, Haryana, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9519-6338","authenticated-orcid":false,"given":"Alaa A. A.","family":"Aljabali","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Yarmouk University, Irbid 21163, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0164-8753","authenticated-orcid":false,"given":"Eman","family":"Hajeer","sequence":"additional","affiliation":[{"name":"Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PL, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9549-8504","authenticated-orcid":false,"given":"Manfredi","family":"Rizzo","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Childcare, Internal Medicine and Medical Specialties, School of Medicine, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/s41581-023-00784-z","article-title":"Differences in the epidemiology, management and outcomes of kidney disease in men and women","volume":"20","author":"Hesnaye","year":"2024","journal-title":"Nat. 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