Dapagliflozin modulates plasma lipidomic profile and urinary metabolite excretion in type 2 diabetes
Authors' conclusion
DAPA treatment has major effects on the plasma lipidomic and the urine metabolomic profiles, with significant increased renal excretion of several metabolites, especially amino-acids, independently of increased diuresis. These data offer insights into the complex metabolic pathways leading to kidney protection by SGLT2 inhibitors.
Study context
- Population
- Subjects with T2D and hypertension
- Comparison
- Dapagliflozin (DAPA) 10 mg/day vs hydrochlorothiazide 12.5 mg/day for four weeks
- Primary endpoint
- Changes in plasma metabolomic/lipidomic profile and urinary excretion of metabolites, by high resolution mass spectrometry in fasting plasma and 24-h urine
- Follow-up
- Before and after four weeks of treatment
Methodological detailstwo-armed, parallel-design
- Two-armed
- Parallel-design
Primary result
As reported in the abstract
four weeks
- Vs hydrochlorothiazide, DAPA significantly increased plasma isoleucine, methionine, citrate, β-hydroxybutyrate and decreased lactate
- DAPA induced plasma lipid remodeling towards a significant rise in free fatty acids (FFAs) and some sphingomyelins and lysophosphatidylcholines containing these fatty acids
- Significant change in plasma medium- and short-chain acylcarnitines, positively correlated with changes in plasma FFAs and β-hydroxybutyrate
- DAPA, but not hydrochlorothiazide, significantly increased 24-h urinary excretion of several amino-acids, lactate, TCA cycle metabolites, β-hydroxybutyrate and electrolytes, except for a decrease in malate excretion
Original publication
Dapagliflozin modulates plasma lipidomic profile and urinary metabolite excretion in type 2 diabetes. Cardiovasc Diabetol. Published 30 December 2025. doi:10.
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