Effect of dapagliflozin on urine metabolome in patients with
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Inhibitors of sodium-glucose cotransporters-2 have cardio- and renoprotective properties. However, the underlying mechanisms remain indeterminate.

This study aimed to evaluate the effect of dapagliflozin on renal metabolism assessed by urine metabolome analysis in patients with type 2 diabetes. Eighty patients with HbA1c more than 7% on metformin monotherapy were prospectively enrolled.

Fifty patients were treated with dapagliflozin for 3 months. To exclude that the changes observed in urine metabolome were merely the result of the improvement in glycemia, 30 patients treated with insulin degludec were used for comparison.

Changes in urine metabolic profile before and after the administration of dapagliflozin and insulin degludec were assessed by Proton-Nuclear Magnetic Resonance spectroscopy (1H-NMR).

-- In multivariate analysis urine metabolome was significantly altered by dapagliflozin 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.

Conclusively, 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.

Source: https://academic.oup.com/jcem/advance-article-abstract/doi/10.1210/clinem/dgab086/6139141?redirectedFrom=fulltext