Effect of Dapagliflozin on Urine Metabolome in Patients with Type 2 Diabetes.
J Clin Endocrinol Metab
; 106(5): 1269-1283, 2021 04 23.
Article
em En
| MEDLINE
| ID: mdl-33592103
ABSTRACT
CONTEXT Inhibitors of sodium-glucose cotransporters-2 have cardio- and renoprotective properties. However, the underlying mechanisms remain indeterminate. OBJECTIVE:
To evaluate the effect of dapagliflozin on renal metabolism assessed by urine metabolome analysis in patients with type 2 diabetes.DESIGN:
Prospective cohort study.SETTING:
Outpatient diabetes clinic of a tertiary academic center. PATIENTS Eighty patients with hemoglobin A1c > 7% on metformin monotherapy were prospectively enrolled. INTERVENTION 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. MAIN OUTCOMEMEASURE:
Changes in urine metabolic profile before and after the administration of dapagliflozin and insulin degludec were assessed by proton-nuclear magnetic resonance spectroscopy.RESULTS:
In multivariate analysis urine metabolome was significantly altered by dapagliflozin (R2Xâ =â 0.819, R2Yâ =â 0.627, Q2Yâ =â 0.362, and coefficient of variation analysis of variance, Pâ <â 0.001) but not insulin. After dapagliflozin, the urine concentrations of ketone bodies, lactate, branched chain amino acids (Pâ <â 0.001), betaine, myo-inositol (Pâ <â 0001), and N-methylhydantoin (Pâ <â 0.005) were significantly increased. Additionally, the urine levels of alanine, creatine, sarcosine, and citrate were also increased (Pâ <â 0001, Pâ <0.0001, and Pâ <0.0005, respectively) whereas anserine decreased (Pâ <â 0005).CONCLUSIONS:
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Compostos Benzidrílicos
/
Diabetes Mellitus Tipo 2
/
Metaboloma
/
Glucosídeos
Tipo de estudo:
Observational_studies
Limite:
Aged
/
Female
/
Humans
/
Male
/
Middle aged
País/Região como assunto:
Europa
Idioma:
En
Revista:
J Clin Endocrinol Metab
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Grécia