达格列净与二甲双胍联合利拉鲁肽对2型糖尿病肾病患者内脏脂肪及肾功能影响

Effect of dapagliflozin and metformin combined with liraglutide on visceral fat and renal function in patients with type 2 diabetic nephropathy

目的 探究二甲双胍与达格列净联合利拉鲁肽对2型糖尿病肾病患者内脏脂肪及肾功能的影响。方法 回顾性选择2022年12月至2023年12月于宁波大学附属第一医院治疗的2型糖尿病肾病患者159例,经倾向评分匹配后最终纳入研究的试验组和对照组患者均为51例,试验组患者行二甲双胍、达格列净联合利拉鲁肽治疗,对照组患者行二甲双胍、达格列净联合治疗。用药前和用药6个月后检测患者的血糖指标、血脂指标和肾功能指标、测量内脏脂肪面积、并对比不良反应发生情况。结果 空腹血糖(FPG)、餐后2 h血糖(2 h PG)、糖化血红蛋白(Hb A_lc)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)和内脏脂肪面积方面,两组治疗后均有所降低,试验组数据分别为(6.35±1.05) mmol·L^(-1)、(7.43±1.36) mmol·L^(-1)、(7.15±1.79)%、(4.15±1.18) mmol·L^(-1)、(1.17±0.33) mmol·L^(-1)、(2.75±0.53) mmol·L^(-1)和(74.12±5.43) cm^(2),低于对照组(6.83±1.11) mmol·L^(-1)、(9.58±1.47) mmol·L^(-1)、(7.98±1.87)%、(4.68±1.23) mmol·L^(-1)、(1.87±0.51) mmol·L^(-1)、(3.27±0.64) mmol·L^(-1)和(79.66±6.81) cm^(2),差异有统计学意义(t=2.243、7.667、2.290、2.220、8.229、4.469、4.542,P=0.027、<0.001、0.024、0.029、<0.001、<0.001、<0.001);治疗后两组尿素氮(BUN)、血肌酐(Scr)、β_(2)-微球蛋白(β_(2)-MG)含量、尿白蛋白/肌酐比值(UACR)均较治疗前降低,试验组数据分别为(7.01±1.25) mmol·L^(-1)、(52.12±8.81)μmol·L^(-1)、(3.75±0.88) mg·L^(-1)和(25.57±2.86) mg·g^(-1),低于对照组(7.53±1.28) mmol·L^(-1)、(57.47±9.18)μmol·L^(-1)、(4.95±1.58) mg·L^(-1)、(28.34±3.02) mg·g^(-1)(t=2.076、3.003、4.738、4.756,P=0.040、0.003、<0.001、<0.001);治疗后两组高密度脂蛋白胆固醇(HDL-C)有所升高,且试验组(1.42±0.21) mmol·L^(-1)高于对照组(1.29±0.16) mmol·L^(-1),差异有统计学意义(t=3.517,P<0.001);两组治疗期间均有低血糖、皮疹、胃肠道反应等不良反应发生,试验组发生率分别为9.80%、7.84%、9.80%,对照组发生率分别为5.88%、7.84%、9.80%,差异无统计学意义(χ^(2)=0.136、0.136、0.111,P=0.713、0.713、0.739)。结论 对2型糖尿病肾病患者予以二甲双胍、达格列净结合利拉鲁肽治疗,能显著降低患者的血糖和血脂水平,在减少内脏脂肪的同时还能减轻肾损伤,并具有较高的安全性。

Objective To explore the effect of dapagliflozin and metformin in combination with liraglutide on visceral fat and renal function in patients with type 2 diabetic nephropathy.Methods A total of 159 patients with type 2 diabetic nephropathy treated in the First Affiliated Hospital of Ningbo University from December 2022 to December 2023 were retrospectively selected as the research subjects.After PSM matching,102 patients were included in this study and divided into the experimental group and the control group,with 51 patients in each group.The patients in the experimental group were treated with metformin and dapagliflozin combined with liraglutide while those in the control group were treated with metformin and dapagliflozin in combination.The patient’s blood sugar indexes,blood lipid indexes,renal function indexes and the fat content of the heart,liver and kidney was determined before medication and 6 months after the end of the medication.Results The levels of FPG,2 hPG,HbAlc,TC,TG,LDL-C,and visceral fat area were all decreased after treatment,and they were(6.35±1.05)mmol·L^(-1),(7.43±1.36)mmol·L^(-1),(7.15±1.79)%,(4.15±1.18)mmol·L^(-1),(1.17±0.33)mmol·L^(-1),(2.75±0.53)mmol·L^(-1),and(74.12±5.43)cm^(2) in the experimental group,which were lower than those of(6.83±1.11)mmol·L^(-1),(9.58±1.47)mmol·L^(-1),(7.98±1.87)%,(4.68±1.23)mmol·L^(-1),(1.87±0.51)mmol·L^(-1),(3.27±0.64)mmol·L^(-1) and(79.66±6.81)cm^(2) in the control(t=2.243,7.667,2.290,2.220,8.229,4.469,4.542,all P<0.05).The serum levels of nitrogen(BUN),blood creatinine(Scr),β2-microglobulin(β2-MG)and urinary microalbumin to creatinine ratio(UACR)were all decreased after treatment,and they were(7.01±1.25)mmol·L^(-1),(52.12±8.81)μmol·L^(-1),(3.75±0.88)mg·L^(-1) and(25.57±2.86)mg·g^(-1) in the experimental group,which were lower than those of(7.53±1.28)mmol·L^(-1),(57.47±9.18)μmol·L^(-1),(4.95±1.58)mg·L^(-1) and(28.34±3.02)mg·g^(-1)(t=2.076,3.003,4.738,4.756,all P<0.05).The level of high-density lipoprotein cholesterol(HDL-C)was increased in both groups after treatment and it was significantly higher in the experimental group than in the control((1.42±0.21)mmol·L^(-1) vs(1.29±0.16)mmol·L^(-1))(t=3.517,P<0.001).Adverse reaction such as hypoglycemia,rash,and gastrointestinal reactions occurred in both groups after treatment.Their occurring rates in the experimental group were 9.80%,7.84%,and 9.80%respectively,and they were 5.88%,7.84%,and 9.80%in the control.The difference was not statistically significant(χ^(2)=0.136,0.136,0.111,P=0.713,0.713,0.739).Conclusion Treatment of patients with type 2 diabetic nephropathy by using dapagliflozin and metformin combined with liraglutide can significantly decrease the blood sugar and blood lipid levels and reduce visceral fat to result in reduction of kidney damage.