Effect of Dapagliflozin on Urine Metabolome in Patients with Type 2 Diabetes.
Aged
Benzhydryl Compounds
/ administration & dosage
Blood Glucose
/ drug effects
Diabetes Mellitus, Type 2
/ drug therapy
Female
Glucosides
/ administration & dosage
Glycated Hemoglobin
/ drug effects
Greece
Humans
Male
Metabolome
/ drug effects
Metformin
/ administration & dosage
Middle Aged
Treatment Outcome
Urinalysis
branched chain amino acids
dapagliflozin
kidney
metabolomics
osmolytes
Journal
The Journal of clinical endocrinology and metabolism
ISSN: 1945-7197
Titre abrégé: J Clin Endocrinol Metab
Pays: United States
ID NLM: 0375362
Informations de publication
Date de publication:
23 04 2021
23 04 2021
Historique:
received:
12
11
2020
pubmed:
17
2
2021
medline:
28
9
2021
entrez:
16
2
2021
Statut:
ppublish
Résumé
Inhibitors of sodium-glucose cotransporters-2 have cardio- and renoprotective properties. However, the underlying mechanisms remain indeterminate. To evaluate the effect of dapagliflozin on renal metabolism assessed by urine metabolome analysis in patients with type 2 diabetes. Prospective cohort study. 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. 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. 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 (P < 0.001), betaine, myo-inositol (P < 0001), and N-methylhydantoin (P < 0.005) were significantly increased. Additionally, the urine levels of alanine, creatine, sarcosine, and citrate were also increased (P < 0001, P <0.0001, and P <0.0005, respectively) whereas anserine decreased (P < 0005). 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.
Identifiants
pubmed: 33592103
pii: 6139141
doi: 10.1210/clinem/dgab086
pmc: PMC8063232
doi:
Substances chimiques
Benzhydryl Compounds
0
Blood Glucose
0
Glucosides
0
Glycated Hemoglobin A
0
dapagliflozin
1ULL0QJ8UC
Metformin
9100L32L2N
Banques de données
ClinicalTrials.gov
['NCT02798757']
Types de publication
Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1269-1283Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.
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