Third Internal Medicine Department, General Hospital of Nikaia, Athens, Greece.
Department of Internal Medicine, University of Ioannina, Ioannina, Greece.
J Clin Endocrinol Metab. 2021 Apr 23;106(5):1269-1283. doi: 10.1210/clinem/dgab086.
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.
钠-葡萄糖共转运蛋白-2 抑制剂具有心脏和肾脏保护作用。然而，其潜在机制尚不确定。
评估达格列净对 2 型糖尿病患者尿液代谢组分析评估的肾脏代谢的影响。
前瞻性队列研究。
三级学术中心的门诊糖尿病诊所。
80 例接受二甲双胍单药治疗、糖化血红蛋白（HbA1c）>7%的患者被前瞻性纳入。
50 例患者接受达格列净治疗 3 个月。为排除观察到的尿液代谢组变化仅仅是血糖改善的结果，30 例接受胰岛素地特胰岛素治疗的患者用于比较。
使用质子核磁共振波谱法评估达格列净和胰岛素地特胰岛素给药前后尿液代谢谱的变化。
在多变量分析中，达格列净显著改变了尿液代谢组（R2X=0.819，R2Y=0.627，Q2Y=0.362，方差分析协方差分析，P<0.001），但胰岛素没有。达格列净后，尿液中酮体、乳酸、支链氨基酸（P<0.001）、甜菜碱、肌醇（P<0.001）和 N-甲基海因（P<0.005）的浓度显著升高。此外，尿液中丙氨酸、肌酸、肌氨酸和柠檬酸的水平也升高（P<0.0001，P<0.0001 和 P<0.0005，分别），而鹅肌肽降低（P<0.0005）。
达格列净以不依赖于降低血糖的方式显著影响 2 型糖尿病患者的尿液代谢组。观察到的大多数变化可被认为是有益的，并可能有助于达格列净的肾脏保护作用。
