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Effect of Dapagliflozin on Urine Metabolome in Patients with Type 2 Diabetes

Evdoxia Bletsa1, Sebastien Filippas-Dekouan2, Christina Kostara3

  • 1Third Internal Medicine Department, General Hospital of Nikaia, Athens, Greece.

The Journal of Clinical Endocrinology and Metabolism
|February 16, 2021
PubMed
Abstract

Insights

Sodium-glucose cotransporter-2 inhibitors like dapagliflozin alter urine metabolome in type 2 diabetes patients. These changes, independent of glucose lowering, may explain dapagliflozin's cardio- and renoprotective effects.

Area of Science:

  • Nephrology
  • Endocrinology
  • Metabolomics

Background:

  • Sodium-glucose cotransporter-2 (SGLT2) inhibitors demonstrate cardio- and renoprotective effects in patients with type 2 diabetes.
  • The precise mechanisms underlying these benefits remain incompletely understood.

Purpose of the Study:

  • To investigate the impact of dapagliflozin on the renal metabolic profile of patients with type 2 diabetes using urine metabolome analysis.
  • To determine if observed metabolic changes are independent of glycemic control.

Main Methods:

  • A prospective cohort study involving 80 patients with type 2 diabetes (hemoglobin A1c > 7%) on metformin monotherapy.
  • Urine metabolome analysis using proton-nuclear magnetic resonance (NMR) spectroscopy before and after 3 months of treatment with either dapagliflozin (n=50) or insulin degludec (n=30).

Main Results:

  • Dapagliflozin significantly altered the urine metabolome (multivariate analysis, P < 0.001), while insulin degludec did not.
  • Treatment with dapagliflozin led to significant increases in urine concentrations of ketone bodies, lactate, branched-chain amino acids, betaine, myo-inositol, N-methylhydantoin, alanine, creatine, sarcosine, and citrate.
  • Anserine levels significantly decreased following dapagliflozin treatment.

Conclusions:

  • Dapagliflozin induces significant, glucose-lowering-independent changes in the urine metabolome of patients with type 2 diabetes.
  • The observed metabolic alterations, including increased ketone bodies and altered amino acid profiles, are potentially beneficial and may contribute to the renoprotective properties of dapagliflozin.
Keywords:
branched chain amino acidsdapagliflozinkidneymetabolomicsosmolytes

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