SGLT2 inhibition modulates metabolic, vascular, and inflammatory molecular markers in the kidney in youth with type 1 diabetes.
A diabetes drug reshapes kidney cell metabolism in young people with type 1 diabetes, correcting over half of disease-linked gene changes.
The ATTEMPT RCT randomized 98 youths aged 12-21 with T1D and hyperfiltration to dapagliflozin vs placebo for 16 weeks, with sequential kidney biopsies analyzed by single-cell RNA sequencing revealing coordinated transcriptional improvements across nephron, vascular, and immune compartments. SGLT2 inhibition down-regulated glycolysis, gluconeogenesis, and oxidative stress in proximal tubule cells, normalized medullary oxygenation, and shifted >55% of T1D-dysregulated genes toward healthy control expression—the first mechanistic evidence of SGLT2i renoprotection in youth with T1D.
What the study was
- Study design
- randomized controlled trial
- Population
- youth with type 1 diabetes and hyperfiltration (age 12-21)
- Sample size
- 98
- Category
- Treatment Innovation
- Maturity
- Potentially Practice-Changing
- Journal
- Science Translational Medicine
Why it surfaced
First pediatric T1D RCT with sequential kidney biopsies and single-cell RNAseq; provides mechanistic evidence for SGLT2i renoprotection in a population where kidney protection was previously unestablished, with direct implications for diabetic nephropathy prevention guidelines.
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