SGLT2 inhibitors in autoimmune diseases: emerging therapeutic potential and clinical challenges

Autoimmune diseases (AIDs) are conditions where the immune system mistakenly attacks self-antigens, leading to tissue and organ damage. The exact mechanisms underlying AIDs pathogenesis remain unclear, and effective treatments are currently limited, posing significant therapeutic challenges. Recent...

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Main Authors: Taimin Luo, Liaoyun Zhang, Kun Tu, Gen Li, Hao Su, Guanli Gong, Yilan Huang, Min Li, Xuping Yang
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1589341/full
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author Taimin Luo
Liaoyun Zhang
Kun Tu
Kun Tu
Gen Li
Hao Su
Hao Su
Guanli Gong
Guanli Gong
Yilan Huang
Yilan Huang
Min Li
Min Li
Xuping Yang
Xuping Yang
author_facet Taimin Luo
Liaoyun Zhang
Kun Tu
Kun Tu
Gen Li
Hao Su
Hao Su
Guanli Gong
Guanli Gong
Yilan Huang
Yilan Huang
Min Li
Min Li
Xuping Yang
Xuping Yang
author_sort Taimin Luo
collection DOAJ
description Autoimmune diseases (AIDs) are conditions where the immune system mistakenly attacks self-antigens, leading to tissue and organ damage. The exact mechanisms underlying AIDs pathogenesis remain unclear, and effective treatments are currently limited, posing significant therapeutic challenges. Recent studies suggest that targeting T cell immune metabolism could be a promising approach for treating AIDs. Repurposed type 2 diabetes mellitus (T2DM) medications, which modulate immune metabolic processes, have shown potential in various inflammatory conditions. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, a novel class of oral antidiabetic agents, not only regulate metabolic dysfunction but also offer protective effects on the heart and kidneys. Emerging preclinical evidence indicates that SGLT2 inhibitors possess immunomodulatory properties, highlighting their potential in enhancing T cell-mediated autoimmune therapy. Clinical studies further validate that SGLT2 inhibitors significantly reduce the risk of chronic kidney disease (CKD) progression in non-diabetic patient groups, such as those with chronic glomerulonephritis like IgA nephropathy. This review aims to evaluate current preclinical and clinical research on the impact of SGLT2 inhibitors on the immune system and explore their mechanisms of action relevant to treating AIDs.
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spelling doaj-art-c036201ff4c5467d9d67dc23ace4f3412025-08-20T03:15:03ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.15893411589341SGLT2 inhibitors in autoimmune diseases: emerging therapeutic potential and clinical challengesTaimin Luo0Liaoyun Zhang1Kun Tu2Kun Tu3Gen Li4Hao Su5Hao Su6Guanli Gong7Guanli Gong8Yilan Huang9Yilan Huang10Min Li11Min Li12Xuping Yang13Xuping Yang14Department of Pharmacy, Chengdu Seventh People’s Hospital (Affiliated Cancer Hospital of Chengdu Medical College), Chengdu, ChinaDepartment of pharmacy, Sichuan Provincial Woman’s and Children’s Hospital & The Affliated Women’s and Children’s Hospital of Chengdu Medical College, Chengdu, Sichuan, ChinaDepartment of Pharmacy, The Affiliated Hospital, Southwest Medical University, Luzhou, ChinaSchool of Pharmacy, Southwest Medical University, Luzhou, ChinaDepartment of pharmacy, Sichuan Provincial Woman’s and Children’s Hospital & The Affliated Women’s and Children’s Hospital of Chengdu Medical College, Chengdu, Sichuan, ChinaDepartment of Pharmacy, The Affiliated Hospital, Southwest Medical University, Luzhou, ChinaSchool of Pharmacy, Southwest Medical University, Luzhou, ChinaDepartment of Pharmacy, The Affiliated Hospital, Southwest Medical University, Luzhou, ChinaSchool of Pharmacy, Southwest Medical University, Luzhou, ChinaDepartment of Pharmacy, The Affiliated Hospital, Southwest Medical University, Luzhou, ChinaSchool of Pharmacy, Southwest Medical University, Luzhou, ChinaDepartment of Pharmacy, The Affiliated Hospital, Southwest Medical University, Luzhou, ChinaSchool of Pharmacy, Southwest Medical University, Luzhou, ChinaDepartment of Pharmacy, The Affiliated Hospital, Southwest Medical University, Luzhou, ChinaSchool of Pharmacy, Southwest Medical University, Luzhou, ChinaAutoimmune diseases (AIDs) are conditions where the immune system mistakenly attacks self-antigens, leading to tissue and organ damage. The exact mechanisms underlying AIDs pathogenesis remain unclear, and effective treatments are currently limited, posing significant therapeutic challenges. Recent studies suggest that targeting T cell immune metabolism could be a promising approach for treating AIDs. Repurposed type 2 diabetes mellitus (T2DM) medications, which modulate immune metabolic processes, have shown potential in various inflammatory conditions. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, a novel class of oral antidiabetic agents, not only regulate metabolic dysfunction but also offer protective effects on the heart and kidneys. Emerging preclinical evidence indicates that SGLT2 inhibitors possess immunomodulatory properties, highlighting their potential in enhancing T cell-mediated autoimmune therapy. Clinical studies further validate that SGLT2 inhibitors significantly reduce the risk of chronic kidney disease (CKD) progression in non-diabetic patient groups, such as those with chronic glomerulonephritis like IgA nephropathy. This review aims to evaluate current preclinical and clinical research on the impact of SGLT2 inhibitors on the immune system and explore their mechanisms of action relevant to treating AIDs.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1589341/fullSGLT2 inhibitorsautoimmune diseasesT cellsmetabolic reprogramminginflammatory response
spellingShingle Taimin Luo
Liaoyun Zhang
Kun Tu
Kun Tu
Gen Li
Hao Su
Hao Su
Guanli Gong
Guanli Gong
Yilan Huang
Yilan Huang
Min Li
Min Li
Xuping Yang
Xuping Yang
SGLT2 inhibitors in autoimmune diseases: emerging therapeutic potential and clinical challenges
Frontiers in Immunology
SGLT2 inhibitors
autoimmune diseases
T cells
metabolic reprogramming
inflammatory response
title SGLT2 inhibitors in autoimmune diseases: emerging therapeutic potential and clinical challenges
title_full SGLT2 inhibitors in autoimmune diseases: emerging therapeutic potential and clinical challenges
title_fullStr SGLT2 inhibitors in autoimmune diseases: emerging therapeutic potential and clinical challenges
title_full_unstemmed SGLT2 inhibitors in autoimmune diseases: emerging therapeutic potential and clinical challenges
title_short SGLT2 inhibitors in autoimmune diseases: emerging therapeutic potential and clinical challenges
title_sort sglt2 inhibitors in autoimmune diseases emerging therapeutic potential and clinical challenges
topic SGLT2 inhibitors
autoimmune diseases
T cells
metabolic reprogramming
inflammatory response
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1589341/full
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