Antioxidant Effects of SGLT2 Inhibitors on Cardiovascular–Kidney–Metabolic (CKM) Syndrome
The cardiovascular–kidney–metabolic (CKM) syndrome was recently conceptualized to provide a holistic framework for diagnosing and treating the full spectrum of key age-associated interrelated conditions: overweight/obesity, type 2 diabetes mellitus, acute and chronic kidney disease, and cardiovascul...
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MDPI AG
2025-06-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/14/6/701 |
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| author | Juan Guerrero-Mauvecin Natalia Villar-Gómez Lucia Miño-Izquierdo Adrián Povo-Retana Adrian M. Ramos Gema Ruiz-Hurtado Maria D. Sanchez-Niño Alberto Ortiz Ana B. Sanz |
| author_facet | Juan Guerrero-Mauvecin Natalia Villar-Gómez Lucia Miño-Izquierdo Adrián Povo-Retana Adrian M. Ramos Gema Ruiz-Hurtado Maria D. Sanchez-Niño Alberto Ortiz Ana B. Sanz |
| author_sort | Juan Guerrero-Mauvecin |
| collection | DOAJ |
| description | The cardiovascular–kidney–metabolic (CKM) syndrome was recently conceptualized to provide a holistic framework for diagnosing and treating the full spectrum of key age-associated interrelated conditions: overweight/obesity, type 2 diabetes mellitus, acute and chronic kidney disease, and cardiovascular disease. This conceptualization resulted from epidemiological associations, advances in our understanding of shared and interrelated pathogenic mechanisms, and observations that several drug families improved outcomes in all three components of CKM. Sodium/glucose cotransporter 2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP-1 RA) enhance all CKM spectrum components, although their efficacy varies against specific components. However, the modified mechanisms by these drugs beyond glycemic control in CKM syndrome are poorly understood. We now deeply review the available literature regarding the impact of SGLT2i on oxidative stress and antioxidant defenses in preclinical and clinical studies of type 2 diabetes mellitus, acute and chronic kidney disease, cardiovascular disease, and CKM syndrome. Evidence suggests that SGLT2i may have a secondary antioxidant effect that reduces the vicious cycle of tissue injury—inflammation—tissue injury, even in organs distant from the primary injury. |
| format | Article |
| id | doaj-art-45c569c04cf04753a45ff3794cde72ce |
| institution | Kabale University |
| issn | 2076-3921 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj-art-45c569c04cf04753a45ff3794cde72ce2025-08-20T03:27:26ZengMDPI AGAntioxidants2076-39212025-06-0114670110.3390/antiox14060701Antioxidant Effects of SGLT2 Inhibitors on Cardiovascular–Kidney–Metabolic (CKM) SyndromeJuan Guerrero-Mauvecin0Natalia Villar-Gómez1Lucia Miño-Izquierdo2Adrián Povo-Retana3Adrian M. Ramos4Gema Ruiz-Hurtado5Maria D. Sanchez-Niño6Alberto Ortiz7Ana B. Sanz8Laboratorio de Nefrología Experimental, Instituto de Investigación Sanitaria-Fundacion Jimenez Diaz (IIS-FJD), Universidad Autonoma de Madrid, 28040 Madrid, SpainLaboratorio de Nefrología Experimental, Instituto de Investigación Sanitaria-Fundacion Jimenez Diaz (IIS-FJD), Universidad Autonoma de Madrid, 28040 Madrid, SpainLaboratorio de Nefrología Experimental, Instituto de Investigación Sanitaria-Fundacion Jimenez Diaz (IIS-FJD), Universidad Autonoma de Madrid, 28040 Madrid, SpainDepartamento de Enfermedades Metabólicas e Inmunitarias, Instituto de Investigaciones Biomédicas “Sols-Morreale”, 28029 Madrid, SpainLaboratorio de Nefrología Experimental, Instituto de Investigación Sanitaria-Fundacion Jimenez Diaz (IIS-FJD), Universidad Autonoma de Madrid, 28040 Madrid, SpainRICORS2040, Instituto de Salud Carlos III, 28029 Madrid, SpainLaboratorio de Nefrología Experimental, Instituto de Investigación Sanitaria-Fundacion Jimenez Diaz (IIS-FJD), Universidad Autonoma de Madrid, 28040 Madrid, SpainLaboratorio de Nefrología Experimental, Instituto de Investigación Sanitaria-Fundacion Jimenez Diaz (IIS-FJD), Universidad Autonoma de Madrid, 28040 Madrid, SpainLaboratorio de Nefrología Experimental, Instituto de Investigación Sanitaria-Fundacion Jimenez Diaz (IIS-FJD), Universidad Autonoma de Madrid, 28040 Madrid, SpainThe cardiovascular–kidney–metabolic (CKM) syndrome was recently conceptualized to provide a holistic framework for diagnosing and treating the full spectrum of key age-associated interrelated conditions: overweight/obesity, type 2 diabetes mellitus, acute and chronic kidney disease, and cardiovascular disease. This conceptualization resulted from epidemiological associations, advances in our understanding of shared and interrelated pathogenic mechanisms, and observations that several drug families improved outcomes in all three components of CKM. Sodium/glucose cotransporter 2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP-1 RA) enhance all CKM spectrum components, although their efficacy varies against specific components. However, the modified mechanisms by these drugs beyond glycemic control in CKM syndrome are poorly understood. We now deeply review the available literature regarding the impact of SGLT2i on oxidative stress and antioxidant defenses in preclinical and clinical studies of type 2 diabetes mellitus, acute and chronic kidney disease, cardiovascular disease, and CKM syndrome. Evidence suggests that SGLT2i may have a secondary antioxidant effect that reduces the vicious cycle of tissue injury—inflammation—tissue injury, even in organs distant from the primary injury.https://www.mdpi.com/2076-3921/14/6/701cardiovascular–kidney–metabolic syndrometreatmentSGLT2 inhibitorsoxidative stressantioxidant defenseschronic kidney disease |
| spellingShingle | Juan Guerrero-Mauvecin Natalia Villar-Gómez Lucia Miño-Izquierdo Adrián Povo-Retana Adrian M. Ramos Gema Ruiz-Hurtado Maria D. Sanchez-Niño Alberto Ortiz Ana B. Sanz Antioxidant Effects of SGLT2 Inhibitors on Cardiovascular–Kidney–Metabolic (CKM) Syndrome Antioxidants cardiovascular–kidney–metabolic syndrome treatment SGLT2 inhibitors oxidative stress antioxidant defenses chronic kidney disease |
| title | Antioxidant Effects of SGLT2 Inhibitors on Cardiovascular–Kidney–Metabolic (CKM) Syndrome |
| title_full | Antioxidant Effects of SGLT2 Inhibitors on Cardiovascular–Kidney–Metabolic (CKM) Syndrome |
| title_fullStr | Antioxidant Effects of SGLT2 Inhibitors on Cardiovascular–Kidney–Metabolic (CKM) Syndrome |
| title_full_unstemmed | Antioxidant Effects of SGLT2 Inhibitors on Cardiovascular–Kidney–Metabolic (CKM) Syndrome |
| title_short | Antioxidant Effects of SGLT2 Inhibitors on Cardiovascular–Kidney–Metabolic (CKM) Syndrome |
| title_sort | antioxidant effects of sglt2 inhibitors on cardiovascular kidney metabolic ckm syndrome |
| topic | cardiovascular–kidney–metabolic syndrome treatment SGLT2 inhibitors oxidative stress antioxidant defenses chronic kidney disease |
| url | https://www.mdpi.com/2076-3921/14/6/701 |
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