达格列净联合聚乙二醇洛塞那...病患者的有效性及安全性研究_叶启宝.pdf

基金项目:安徽医科大学校科研基金资助项目(2015xkj061)作者单位:230061安徽医科大学第三附属医院(合肥市第一人民医院滨湖院区)内分泌科通信作者:王国娟,电子信箱:dfwangguojuan 达格列净联合聚乙二醇洛塞那肽治疗超重/肥胖2 型糖尿病患者的有效性及安全性研究叶启宝陈望李颖张倩倩陈丽王国娟摘要目的探讨达格列净联合聚乙二醇洛塞那肽治疗超重/肥胖 2 型糖尿病的有效性及安全性。方法选择 2020 年 4月 2021 年 1 月笔者医院收治的超重/肥胖 2 型糖尿病患者 80 例,分为对照组(n=40)和观察组(n=40)。对照组为达格列净联合二甲双胍治疗,观察组在对照组的基础上加用聚乙二醇洛塞那肽治疗。两组均治疗 12 周,测量治疗前后两组患者的体重、身高、体重指数(body mass index,BMI)、收缩压(systolic blood pressure,SBP)、肝功能、空腹血糖(fasting blood glucose,FPG)、糖化血红蛋白(glycosylated hemoglobin,HbA1c)、空腹胰岛素(fasting insulin,FINS)、空腹 C 肽(fasting C-peptide,FC-P)、计算胰岛素抵抗指数(insulin resistance index,HOMA-IR)、总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、低密度脂蛋白胆固醇(low density lipoprotein-cholesterol,LDL-C)、高密度脂蛋白胆固醇(high density lipoprotein-cholesterol,HDL-C)、尿白蛋白/肌酐(urinary albumin/creatinine,UACR)、估算的肾小球滤过率(estimated glomerular filtration rate,eGFR)等指标,观察并记录治疗期间的不良反应。结果两组治疗后体重、BMI、SBP、FPG、HbA1c、TC、TG、LDL-C、HOMA-IR、UACR 均低于治疗前,HDL-C、FC-P 高于治疗前,差异有统计学意义(P 0.05),尤其是体重、BMI、SBP、FPG、HbA1c、TC、HDL-C、HOMA-IR 方面,观察组改善更明显。两组患者均有 1 例出现低血糖,2 例出现泌尿道感染,观察组有 6 例出现恶心、呕吐等消化道反应,但症状较轻。结论针对超重/肥胖 2 型糖尿病患者,应用聚乙二醇洛塞那肽联合达格列净能更好地控制血糖,减轻体重,调节血压、血脂代谢,保护肾功能,且无严重不良反应发生。关键词 2 型糖尿病肥胖聚乙二醇洛塞那肽达格列净中图分类号R587文献标识码ADOI 10.11969/j.issn.1673-548X.2023.02.023Efficacy and Safety of Dapagliflozin Combined with Polyethylene Glycol Loxenatide in the Treatment of Overweight or Obese Patients withType 2 Diabetes Mellitus.YE Qibao,CHEN Wang,LI Ying,et al.Department of Endocrinology,The Third Affiliated Hospital of AnhuiMedical University(Binhu Hospital,Hefei First Peoples Hospital),Anhui 230061,ChinaAbstractObjectiveTo explore the efficacy and safety of Dapagliflozin combined with Polyethylene glycol loxenatide in the treat-ment of overweight or obese patients with type 2diabetes mellitus.MethodsA total of 80 overweight or obese patients with type 2diabeticmellitus admitted to the Third Affiliated Hospital of Anhui Medical University(Binhu Hospital,Hefei First Peoples Hospital)from April2020 to January 2021 were selected and divided into control group(n=40)and observation group(n=40).The patients of control groupwere treated with Dapagliflozin combined with Metformin,and the patients of observation group were treated with polyethylene glycol lox-enatide on the basis of the control group.Both groups were treated for 12 weeks.The weight,height,body mass index(BMI),systolicblood pressure(SBP),liver function,fasting blood glucose(FPG),glycosylated hemoglobin(HbA1c),fasting insulin(FINS),fastingC-peptide(FC-P),insulin resistance index(HOMA-IR),total cholesterol(TC),triglyceride(TG),low density lipoprotein-cho-lesterol(LDL-C),high density lipoprotein-cholesterol(HDL-C),urinary albumin/creatinine(UACR),estimated glomerular filtra-tion rate(eGFR)were measured before and after treatment.Adverse reactions during treatment were observed and recorded.Adverse re-actions during treatment were observed and recorded.ResultsAfter treatment,the weight,BMI,SBP,FPG,HbA1c,TC,TG,LDL-C,HOMA-IR and UACR of the two groups were lower than those before treatment,and HDL-C and FC-P were higher than those be-fore treatment,the differences were statistically significant(P 7%;BMI24kg/m2。排除标准:糖尿病的急性并发症(糖尿病酮症酸中毒、糖尿病高渗状态、低血糖症等);感染及严重的心脏、脑、肝脏、肾脏等并发症;妊娠期糖尿病。本研究通过笔者医院医学伦理学委员会批准(伦理审批号:2021432),患者及其家属均签署知情同意书。2.研究方法:所有患者入组时均为同一名护士测量身高、体重、血压,并计算体重指数(BMI);测定丙氨酸氨基转移酶(alanine aminotransferase,ALT)、天门冬氨酸氨基转移酶(aspartate transaminase,AST);总胆固醇(total cholesterol,TC)、甘油三酯(triglycer-ide,TG)、低密度脂蛋白胆固醇(low density lipoprotein-cholesterol,LDL-C)、高 密 度 脂 蛋 白 胆 固 醇(highdensity lipoprotein-cholesterol,HDL-C);空腹血糖(fasting blood glucose,FPG)、HbA1c、尿白蛋白/肌酐(urinary albumin/creatinine,UACR)、估算的肾小球滤过率(estimated glomerular filtration rate,eGFR);测定空腹 C 肽(fasting C-peptide,FC-P)、空腹胰岛素(fasting insulin,FINS),计算稳态模型胰岛素抵抗指数(HOMA-IR=FPG FINS/22.5),所有患者均接受健康教育,适当运动。入院后对照组患者停用所有降糖药物(二甲双胍缓释片 500mg 每日两次除外),予以达格列净(无锡阿斯利康制药有限公司)10mg 每日一次,早餐前口服。观察组在对照组的基础上加用聚乙二醇洛塞那肽注射液(江苏豪森医药集团有限公司)0.2mg 每周 1 次,皮下注射。所有入选病例均完成 12 周的观察。出院后患者每周固定 3 天自我监测空腹及餐后指尖血糖,每月复查尿常规,并记录:有无低血糖情况,低血糖判断标准为血糖3.9mmol/L伴或不伴有心慌、手抖、出冷汗、乏力等症状;有无恶心、呕吐等胃肠道反应;有无尿频、尿急、尿痛等不良反应。治疗 12 周后复查入组时所有指标。3.统计学方法:应用 SPSS 21.0 统计学软件对数据进行统计分析。计量资料以均数 标准差(x s)表示,组间比较采用 t 检验,计数资料以例数(百分比)(%)表示,组间比较采用 2检验,以 P 0.05),具有可比性,详见表 1。511医学研究杂志 2023 年 2 月第 52 卷第 2 期论著表 1两组患者基线资料的比较n(%),x s项目对照组(n=40)观察组(n=40)t/2P年龄(岁)52.0 11.653.9 11.8-0.9050.378男性31(77.5)32(80.0)0.0001.100体重(kg)75.8 7.675.4 8.10.3040.764BMI(kg/m2)28.3 2.728.1 2.90.3040.751SBP(mmHg)131.3 11.0 132.1 10.4-0.4010.589FPG(mmol/L)8.3 2.68.1 1.80.3680.614HbA1c(%)8.7 0.98.7 0.80.5310.587FC-P(ng/ml)1.0 0.61.1 0.70.7470.456FINS(IU/ml)18.9 4.119.4 4.2-0.0470.963HOMA-IR7.0 2.17.0 1.30.8950.925TC(mmol/L)5.0 1.34.9 1.01.6650.098TG(mmol/L)3.4 1.12.6 0.91.0230.309LDL-C(mmol/L)3.1 0.83.2 0.70.5210.603HDL-C(mmol/L)1.2 0.21.3 0.5-1.8180.072AST(U/L)20.4 12.921.7 11.50.5260.600ALT(U/L)23.3 12.521.4 7.41.2560.312UACR(mg/mmol)30.6 3.131.5 3.00.1050.618eGFRml/(min 1.73m2)108.6 12.1 108.8 12.2-0.0820.935 2.两组治疗前后各项指标的变化比较:与治疗前比较,两组患者治疗 12 周后,体重、BMI、SBP、FPG、HbA1c、TC、TG、LDL-C、HOMA-IR、UACR 均明