Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2025 May 18;14(10):3533.
doi: 10.3390/jcm14103533.

SGLT2 Inhibitors in Glomerulonephritis: Beyond Nephroprotection?

Lucia Del Vecchio  1 , Silvia Peiti  1 , Giulio Pucci Bella  1 , Francesco Locatelli  2
Affiliations
Review

SGLT2 Inhibitors in Glomerulonephritis: Beyond Nephroprotection?

Lucia Del Vecchio et al. J Clin Med. .

Abstract

Sodium-glucose cotransporter 2 (SGLT2) inhibitors, initially developed for glycaemic control in type 2 diabetes, have demonstrated substantial renal and cardiovascular protective effects across various chronic kidney diseases (CKD), including glomerulonephritis. Beyond their established haemodynamic and metabolic benefits, recent evidence points to additional mechanisms of action potentially relevant to immune-mediated kidney diseases, such as the modulation of inflammation, immunometabolism, and oxidative stress. Randomised clinical trials (DAPA-CKD and EMPA-KIDNEY) and real-world observational studies consistently show that SGLT2 inhibitors reduce proteinuria and slow estimated glomerular filtration rate (eGFR) decline in patients with glomerulonephritis, including IgA nephropathy and focal segmental glomerulosclerosis. These benefits may extend to patients with stable immunosuppression. Further data are needed in this subgroup. Importantly, SGLT2 inhibitors display a favourable safety profile, even among those with immunosuppressed status. Again, further evidence is awaited in this respect. Despite these promising findings, unanswered questions remain regarding their efficacy in nephrotic syndrome, early-stage disease, and in comparison or combination with other supportive therapies. Overall, the evolving evidence supports the inclusion of SGLT2 inhibitors as a key component of supportive therapy in glomerulonephritis, with potential benefits extending beyond proteinuria reduction.

Keywords: IgA nephropathy; SGLT2 inhibitors; chronic kidney disease; glomerulonephritis; immunosuppression; lupus nephritis; proteinuria.

PubMed Disclaimer

Conflict of interest statement

S.P., G.P.B. and F.L declare no conflicts of interest. L.D.V. received speaker fees at meetings with the indirect support of Bayer, Astra Zeneca, Boehringer, and Vifor. The grant was not involved in the study design, collection, or analysis, nor with the interpretation of the data, the writing of this article, or the decision to submit it for publication.

Figures

Figure 1
Figure 1
Possible beneficial effects of SGLT2 inhibitors in patients with glomerulonephritis.
Figure 2
Figure 2
Study design of DAPA-CKD [27] and EMPA-KIDNEY [28] focusing on glomerulonephritis. CV, cardiovascular; RAS, renin angiotensin system; GN, glomerulonephritis; *, following protocol amendment.
Figure 3
Figure 3
The percentage distribution of different types of glomerulonephritis in DAPA-CKD [31], EMPA-KIDNEY [34], and in observational study of the Immunonephrology Working Group of the European Renal Society [33]. IgAN, IgA Nephropathy; FSGS, focal segmental glomerulonephritis; MN, membranous nephropathy; MCD, minimal change disease; ANCA VAS, anti-neutrophil cytoplasm antibodies vasculitis; LN, lupus nephritis.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Rieg T., Masuda T., Gerasimova M., Mayoux E., Platt K., Powell D.R., Thomson S.C., Koepsell H., Vallon V. Increase in SGLT1-mediated transport explains renal glucose reabsorption during genetic and pharmacological SGLT2 inhibition in euglycemia. Am. J. Physiol. Physiol. 2014;306:F188–F193. doi: 10.1152/ajprenal.00518.2013. - DOI - PMC - PubMed
    1. Zhang Y., Thai K., Kepecs D.M., Gilbert R.E. Sodium-Glucose Linked Cotransporter-2 inhibition does not attenuate disease progression in the rat remnant kidney model of chronic kidney disease. PLoS ONE. 2016;11:e0144640. doi: 10.1371/journal.pone.0144640. - DOI - PMC - PubMed
    1. Rajasekeran H., Reich H.N., Hladunewich M.A., Cattran D., Lovshin J.A., Lytvyn Y., Bjornstad P., Lai V., Tse J., Cham L., et al. Dapagliflozin in focal segmental glomerulosclerosis: A combined hu-man-rodent pilot study. Am. J. Physiol. Renal Physiol. 2018;314:F412–F422. doi: 10.1152/ajprenal.00445.2017. - DOI - PMC - PubMed
    1. Heerspink H.J.L., Perkins B.A., Fitchett D.H., Husain M., Cherney D.Z.I. Sodium glucose cotransporter 2 inhibitors in the treatment of diabetes mellitus: Cardiovascular and kidney effects, potential mechanisms, and clinical applications. Circulation. 2016;134:752–772. doi: 10.1161/CIRCULATIONAHA.116.021887. - DOI - PubMed
    1. Schönberger E., Mihaljević V., Steiner K., Šarić S., Kurevija T., Majnarić L.T., Ćurčić I.B., Canecki-Varžić S. Immunomodulatory effects of SGLT2 inhibitors-targeting inflammation and oxidative stress in aging. Int. J. Environ. Res. Public Health. 2023;20:6671. doi: 10.3390/ijerph20176671. - DOI - PMC - PubMed

LinkOut - more resources