Sitagliptin reduces the urine albumin-to-creatinine ratio in type 2 diabetes through decreasing both blood pressure and estimated glomerular filtration rate 西格列汀通过降低2型糖尿病患者的血压以及估算的肾小球滤过率来减少尿白蛋白/肌酐的比值

Background We investigated the change in the urine albumin-to-creatinine ratio (ACR) to examine the effect of sitagliptin on diabetic nephropathy. Methods Sitagliptin at a dose of 50 mg was administered to 247 outpatients with type 2 diabetes. Data were collected on the patients' laboratory results (including the ACR), blood pressure, and body weight. Clinical data were compared before and after 3 months' administration of sitagliptin. Results The ACR changed from 150.0 ± 538.6 mg/gCre to 148.3 ± 764.6 mg/gCre over 3 months. In the patients with micro- and macro-albuminuria, the ACR after 3 months significantly decreased compared with the baseline (P = 0.04 and P = 0.02, respectively). The subjects whose ACR decreased experienced significantly larger decreases over the 3-month period in blood pressure and estimated glomerular filtration rate (eGFR) than the other subjects. There was no significant correlation between change in ACR (ΔACR) and change in hemoglobin A1c (ΔHbA1c) during 3 months (r = 0.04, P = 0.59), but there was a significant correlation between change in ΔACR and change in systolic blood pressure (r = 0.16, P = 0.03). Multiple regression analysis revealed that the significant predictors for ΔACR were change in systolic blood pressure (β = 0.21, P = 0.016) and change in eGFR (β = 0.20, P = 0.024) over 3 months (r = 0.35, P = 0.04). Conclusions Sitagliptin reduces the ACR through decreasing both blood pressure and eGFR, with no correlation with a decrease in HbA1c over a 3-month period. These results may reflect the direct action of sitagliptin on the kidneys. 摘要 背景：通过调查尿白蛋白/肌酐比值（ACR）的变化了解西格列汀对糖尿病肾病的影响。 方法：共有247名门诊2型糖尿病患者参加研究，给予西格列汀50 mg/日进行治疗。收集患者的实验室检查结果（包括ACR）、血压以及体重等数据。对比了使用西格列汀治疗前3个月与治疗后3个月的临床数据。 结果：3个月后ACR从150.0 ± 538.6 mg/gCre降至148.3 ± 764.6 mg/gCre。合并微量以及大量蛋白尿的患者治疗3个月后与基线相比较ACR都显著下降（分别P = 0.04与P = 0.02）。3个月后，与其他受试者相比，ACR下降的受试者其血压以及估算的肾小球滤过率（estimated glomerular filtration rate，eGFR）下降程度更大。在3个月期间，ACR的变化（ΔACR）与HbA1c的变化（ΔHbA1c）之间没有显著性的相关性（r = 0.04，P = 0.59），但是ΔACR的变化与收缩压的变化之间具有显著的相关性（r = 0.16，P = 0.03）。3个月后，多元回归分析结果显示，收缩压的变化（β = 0.21，P = 0.016）和eGFR的变化（β = 0.20，P = 0.024）是ΔACR的重要预测因子（r = 0.35，P = 0.04）。 结论：3个月的西格列汀治疗通过降低血压以及eGFR来减少ACR，与HbA1c的下降没有相关性。这些结果可能反映了西格列汀对肾脏具有直接的作用。