Greece: Dapagliflozin Treatment and Urine Metabolome in T2D Patients

Dapagliflozin treatment is associated with a significant change in urine metabolome in patients with type 2 diabetes (T2D) independent of glucose-lowering, finds a recent study. According to the study results, published in the Journal of Clinical Endocrinology & Metabolism, most of the observed changes can be considered beneficial and may contribute to the renoprotective properties of dapagliflozin.

Sodium-glucose cotransporters-2 (SGLT2) inhibitors have cardio- and renoprotective properties. However, there are no determinate underlying mechanisms. Evdoxia Bletsa, Third Internal Medicine Department, General Hospital of Nikaia, Athens, Greece, and colleagues, therefore, conducted the study to evaluate the effect of dapagliflozin on renal metabolism assessed by urine metabolome analysis in patients with type 2 diabetes.

For this purpose, the researchers performed a prospective cohort study in an outpatient diabetes clinic of a tertiary academic center. Eighty patients with hemoglobin A1c > 7% on metformin monotherapy were prospectively enrolled.

Fifty patients were treated with dapagliflozin for 3 months. Thirty patients treated with insulin degludec were used for comparison, to exclude that the changes observed in urine metabolome were merely the result of the improvement in glycemia.

Changes in urine metabolic profile before and after the administration of dapagliflozin and insulin degludec were assessed by proton-nuclear magnetic resonance spectroscopy.

Key Findings of the Study

• In multivariate analysis, urine metabolome was significantly altered by dapagliflozin (R²X = 0.819, R²Y = 0.627, Q²Y = 0.362, and coefficient of variation analysis of variance, P < 0.001) but not insulin.
• After dapagliflozin, the urine concentrations of ketone bodies, lactate, branched chain amino acids, betaine, myo-inositol, and N-methylhydantoin were significantly increased.
• Additionally, the urine levels of alanine, creatine, sarcosine, and citrate were also increased whereas anserine decreased.

"Dapagliflozin significantly affects urine metabolome in patients with type 2 diabetes in a glucose lowering-independent way. Most of the observed changes can be considered beneficial and may contribute to the renoprotective properties of dapagliflozin," wrote the authors.

"Further studies are needed to confirm our results and to explore the mechanisms that underlie them," they concluded.

Reference

The study titled, "Effect of Dapagliflozin on Urine Metabolome in Patients with Type 2 Diabetes," is published in the Journal of Clinical Endocrinology & Metabolism.

DOI: https://academic.oup.com/jcem/advance-article/doi/10.1210/clinem/dgab086/6139141