Treatment with dapagliflozin and empagliflozin reduces concentrations of N4-acetylcytidine in plasma, a biomarker associated with vascular damage
Authors' conclusion
Treatment with dapagliflozin and empagliflozin reduced plasma concentrations of ac4C, which was correlated with parameters for vascular health.
Study context
- Population
- Diabetic patients; plasma and 24-hour urine samples before and after treatment48 + 24 diabetic patients
- Comparison
- SGLT2 inhibitors (dapagliflozin or empagliflozin) vs placebo; confirmation: empagliflozin + linagliptin vs metformin + insulin glargine
- SGLT2 inhibitorsn = 48
- Outcome
- Changes in plasma metabolites with SGLT2 inhibitors
Methodological detailsuntargeted metabolomics, secondary analysis of two randomized, double-blind, placebo-controlled, cross-over trials, confirmation in a randomized, controlled, parallel-arm, open-label, single centre study
- Untargeted metabolomics
- Secondary analysis of two randomized, double-blind, placebo-controlled, cross-over trials
- Confirmation in a randomized, controlled, parallel-arm, open-label, single centre study
Main finding
As reported in the abstract
- Plasma ac4C reduced by SGLT2 inhibitors (log2fc), adj. p < 0.001; not by non-SGLT2 inhibiting glucose lowering treatment
- - 0.32
- Plasma glucose reduced (log2fc), adj. p < 0.01
- - 0.23
- Plasma uric acid reduced (log2fc), adj. p < 0.001
- - 0.23
- Plasma 3-hydroxybutyric acid increased (log2fc), adj. p < 0.001
- 0.84
- Plasma 3-hydroxybutyrylcarnitine increased (log2fc), adj. p < 0.001
- 0.57
Further findings
Urinary ac4C
- Reduction of urinary ac4C corresponded to its reduction in plasma with SGLT2 inhibitors
Vascular parameters and plasma ac4C
- Wall thickness of retinal arterioles and central systolic blood pressure significantly correlated to plasma ac4C
Original publication
Treatment with dapagliflozin and empagliflozin reduces concentrations of N4-acetylcytidine in plasma, a biomarker associated with vascular damage. Cardiovasc Diabetol. Published 24 July 2026. doi:10.
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