Abstract:

Objective　To observe the effect of dagliprazin combined with insulin degludec and liraglutide injection in the treatment of patients with diabetic nephropathy (DN) and poor blood glucose control. Methods　A total of 167 patients with DN and poor blood glucose control treated at Hanzhong Nanzheng District People's Hospital from February 2022 to February 2024 were selected for the randomized controlled trial, and were divided into a study group (83 cases) and a control group (84 cases) by the random number table method. There were 47 males and 36 females in the study group; they were (57.39±8.16) years old; their disease course was (12.51±2.23) years; there were 48 cases of DN stage Ⅱ and stage 35 cases of stageⅢ. There were 50 males and 34 females in the control group; they were (56.47±8.23) years old; their disease course was (12.36±2.19) years; there were 51 cases of DN stage Ⅱ and 33 cases of stage Ⅲ. The study group were treated with dagliprazin and insulin degludec and liraglutide injection, and the control group with dagaglizin and insulin glargine, for 3 months. The clinical efficacies, renal function, blood glucose, markers of renal injury, peripheral blood cytokines, and the incidence rates of adverse drug reactions were compared between the two groups by t and χ² tests. Results　Before the treatment, there were no statistical differences in the levels of serum creatinine (Scr) and blood urea nitrogen (BUN) and urine albumin-to-creatinine ratio (UACR) between the two groups (all P>0.05). After the treatment, the levels of Scr and BUN and UACR in the study group were lower than those in the control group [(65.24±8.93) μmol/L vs. (76.12±10.43) μmol/L, (6.23±1.12) mmol/L vs. (8.04±1.41) mmol/L, and (92.32±14.26) mg/g vs. (106.21±18.35) mg/g], with statistical differences (all P<0.05). Before the treatment, there were no statistical differences in the levels of fasting blood glucose (FBG), 2-hour postprandial blood glucose (2hPBG), and glycosylated hemoglobin (HbA1c) between the two groups (all P>0.05). After the treatment, the levels of FBG, 2hPBG, and HbA1c in the study group were lower than those in the control group [(6.14±0.76) mmoL/L vs. (7.01±0.89) mmoL/L, (8.16±1.49) mmol/L vs. (9.32±1.73) mmol/L, and (5.21±0.59)% vs. (5.82±0.68)%], with statistical differences (all P<0.05). Before the treatment, there were no statistical differences in the levels of N-acetyl-β-D-glucosidase (NAG), retinol-binding protein (RBP), and neutrophil gelatinase-associated lipocalin (NGAL) between the two groups (all P>0.05). After the treatment, the levels of NAG, RBP, and NGAL in the study group were lower than those in the control group [(15.12±2.54) U/L vs. (18.84±3.01) U/L, (1.08±0.21) mg/L vs. (1.37±0.26) mg/L, and (51.26±8.13) μg/L vs. (62.13±10.28) μg/L], with statistical differences (all P<0.05). Before the treatment, there were no statistical differences in the levels of free fatty acid (FFA) and peroxisome surge activator receptor γ (PPARγ) between the two groups (both P>0.05). After the treatment, the levels of FFA and PPARγ in the study group were lower than those in the control group [(9.03±1.76) μg/L vs. (11.26±2.51) μg/L and (1 306.49±201.43) ng/L vs. (1 148.52±159.47) ng/L], with statistical differences (both P<0.05). The total effective rate of the study group was higher than that of the control group [85.54% (71/83) vs. 70.24% (59/84); P<0.05]. The incidence rates of adverse drug reactions in the study group and the control group were 6.02% (5/83) and 4.76% (4/84), respectively, with no statistical difference (P>0.05). Conclusion　Dagliprazin combined with insulin degludec and liraglutide injection in the treatment of patients with DN and poor blood glucose control is effective, can improve their renal function, blood glucose, markers of kidney injury, and peripheral blood cytokines, and does not increase adverse drug reactions.

Key words:

Diabetic nephropathy, Daglizin, Insulin degludec and liraglutide injection, Blood glucose, Curative effect, Safety

摘要：

目的　观察达格列净联合德谷胰岛素利拉鲁肽注射液治疗血糖控制欠佳的糖尿病肾病（diabetic nephropathy，DN）患者的效果。方法　选取2022年2月至2024年2月汉中市南郑区人民医院收治的167例血糖控制欠佳的DN患者进行随机对照试验。采用随机数字表法将其分为研究组（83例）和对照组（84例）。研究组男47例，女36例，年龄（57.39±8.16）岁，病程（12.51±2.23）年；DN分期：Ⅱ期48例，Ⅲ期35例。对照组男50例，女34例，年龄（56.47±8.23）岁，病程（12.36±2.19）年；DN分期：Ⅱ期51例，Ⅲ期33例。研究组给予达格列净联合德谷胰岛素利拉鲁肽注射液治疗，对照组给予甘精胰岛素联合达格列净治疗。两组均治疗3个月。比较两组临床疗效、肾功能、血糖、肾脏损伤标志物、外周血细胞因子以及药物不良反应的发生情况。采用t检验、χ²检验进行统计分析。结果　治疗前，两组血肌酐（serum creatinine，Scr）、血尿素氮（blood urea nitrogen，BUN）水平和尿白蛋白/肌酐比值（urine albumin-to-creatinine ratio，UACR）比较，差异均无统计学意义（均P>0.05）；治疗后，研究组Scr、BUN水平和UACR均低于对照组［（65.24±8.93）μmol/L比（76.12±10.43）μmol/L、（6.23±1.12）mmol/L比（8.04±1.41）mmol/L、（92.32±14.26）mg/g比（106.21±18.35）mg/g］，差异均有统计学意义（均P<0.05）。治疗前，两组空腹血糖（fasting blood glucose，FBG）、餐后2 h血糖（2-hour postprandial blood glucose，2hPBG）、糖化血红蛋白（glycosylated hemoglobin，HbA1c）水平比较，差异均无统计学意义（均P>0.05）；治疗后，研究组FBG、2hPBG、HbA1c水平均低于对照组［（6.14±0.76）mmoL/L比（7.01±0.89）mmoL/L、（8.16±1.49）mmol/L比（9.32±1.73）mmol/L、（5.21±0.59）%比（5.82±0.68）%］，差异均有统计学意义（均P<0.05）。治疗前，两组N-乙酰-β-D-葡萄糖苷酶（N-acetyl-β-D-glucosidase，NAG）、尿视黄醇结合蛋白（retinol-binding protein，RBP）、尿中性粒细胞明胶酶相关脂质运载蛋白（neutrophil gelatinase-associated lipocalin，NGAL）水平比较，差异均无统计学意义（均P>0.05）；治疗后，研究组NAG、RBP、NGAL水平均低于对照组［（15.12±2.54）U/L比（18.84±3.01）U/L、（1.08±0.21）mg/L比（1.37±0.26）mg/L、（51.26±8.13）μg/L比（62.13±10.28）μg/L］，差异均有统计学意义（均P<0.05）。治疗前，两组游离脂肪酸（free fatty acid，FFA）、过氧化物酶体激增物激活受体γ（peroxisome surge activator receptor γ，PPAR γ）水平比较，差异均无统计学意义（均P>0.05）；治疗后，研究组FFA、PPAR γ水平均低于对照组［（9.03±1.76）μg/L比（11.26±2.51）μg/L、（1 306.49±201.43）ng/L比（1 148.52±159.47）ng/L］，差异均有统计学意义（均P<0.05）。研究组总有效率高于对照组［85.54%（71/83）比70.24%（59/84），P<0.05］。研究组和对照组总药物不良反应发生率分别为6.02%（5/83）和4.76%（4/84），差异无统计学意义（P>0.05）。结论　达格列净联合德谷胰岛素利拉鲁肽注射液治疗血糖控制欠佳的DN患者效果良好，可改善患者肾功能、血糖、肾脏损伤标志物、外周血细胞因子，且不增加药物不良反应。

关键词:

糖尿病肾病, 达格列净, 德谷胰岛素利拉鲁肽注射液, 血糖, 疗效, 安全性