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New research · Endocrinology
Science translational medicine · 1d
Randomized trialScience translational medicine · 2026

SGLT2 inhibition modulates metabolic, vascular, and inflammatory molecular markers in the kidney in youth with type 1 diabetes.

Petter Bjornstad, Ye Ji Choi, Phoom Narongkiatikhun … Matthias Kretzler
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EndocrinologyRandomized trial

Dapagliflozin shifts over half of kidney genes toward healthy patterns in youth with type 1 diabetes.

SGLT2 inhibition modulates metabolic, vascular, and inflammatory molecular markers in the kidney in youth with type 1 diabetes.

Petter Bjornstad et al. · Science translational medicine · 2026
Background

Sodium-glucose cotransporter-2 (SGLT2) inhibitors slow diabetic kidney disease progression, but their intrarenal mechanisms remain incompletely understood, particularly in type 1 diabetes (T1D), where kidney protection has not been definitively established.

Methods

Underwent sequential kidney biopsies, multiparametric kidney MRI, and plasma and urine proteomics.

n = 16,
more than 55%
Results
kidney genes affected by dapagliflozin became more like healthy genes
n = 16,
More results

Single-cell RNA sequencing of 214,415 cells across 27 biopsies revealed coordinated transcriptional shifts across nephron, vascular, and immune compartments.

In the proximal tubule, the primary site of SGLT2 expression, dapagliflozin down-regulated glycolysis, gluconeogenesis, and oxidative stress markers.

More results

Endothelial cells showed reduced profibrotic and inflammatory gene expression with increased protective factors.

Podocytes demonstrated enhanced cytoskeletal reinforcement and suppressed interferon signaling.

“
Conclusion

These convergent molecular mechanisms, metabolic reprogramming, dampened inflammation, and normalized oxygen handling provide hypothesis-generating mechanistic insights into potential kidney-protective mechanisms of SGLT2 inhibitor therapy in youth with T1D.

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