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

**Authors:** Taimin Luo, Liaoyun Zhang, Kun Tu, Gen Li, Hao Su, Guanli Gong, Yilan Huang, Min Li, Xuping Yang

PMC · DOI: 10.3389/fimmu.2025.1589341 · Frontiers in Immunology · 2025-07-03

## TL;DR

This paper reviews how SGLT2 inhibitors, originally used for diabetes, may help treat autoimmune diseases by modulating immune metabolism and protecting organs like the kidneys.

## Contribution

The paper explores the novel application of SGLT2 inhibitors in autoimmune diseases through their immunomodulatory and protective effects.

## Key findings

- SGLT2 inhibitors show immunomodulatory properties that could benefit autoimmune therapy.
- Clinical studies confirm their protective effects on kidney disease in non-diabetic patients.
- Preclinical evidence suggests these inhibitors can regulate immune metabolism relevant to autoimmune diseases.

## Abstract

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.

## Linked entities

- **Diseases:** type 2 diabetes mellitus (MONDO:0005148), chronic kidney disease (MONDO:0005300), IgA nephropathy (MONDO:0005342)

## Full-text entities

- **Genes:** SLC5A2 (solute carrier family 5 member 2) [NCBI Gene 6524] {aka SGLT2}
- **Diseases:** diabetic (MESH:D003920), IgA nephropathy (MESH:D005922), AIDs (MESH:D001327), chronic glomerulonephritis (MESH:D005921), metabolic dysfunction (MESH:D008659), inflammatory (MESH:D007249), CKD (MESH:D051436), T2DM (MESH:D003924)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12267200/full.md

## References

90 references — full list in the complete paper: https://tomesphere.com/paper/PMC12267200/full.md

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Source: https://tomesphere.com/paper/PMC12267200