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

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.

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

Podocytes demonstrated enhanced cytoskeletal reinforcement and suppressed interferon signaling.