胰高糖素样肽-1受体激动剂周制剂对2型糖尿病患者血糖波动的影响:1项多中心、前瞻性研究  

Effect of weekly glucagon-like peptide-1 receptor agonist on improving glycemic variability with continuous glucose monitoring in type 2 diabetes patients: a multi-center, prospective study

作　　者：刘雨晨 周尊海 杨架林 顾明君[4] 吴坚 陆灏[6] 黄珊[7] 陈凤玲[8] 刘志文[9] 苏青[10] 孙姣 李晓华[12] 冯波 刘连勇[14] 鲁瑾 张敏 雷涛[17] 季黎明 赵琳 李小英 Liu Yuchen;Zhou Zunhai;Yang Jialin;Gu Mingjun;Wu Jian;Lu Hao;Huang Shan;Chen Fengling;Liu Zhiwen;Su Qing;Sun Jiao;Li Xiaohua;Feng Bo;Liu Lianyong;Lu Jin;Zhang Min;Lei Tao;Ji Liming;Zhao Lin;Li Xiaoying(Department of Endocrinology and Metabolism,Zhongshan Hospital,Fudan University,Shanghai 200032,China;Department of Endocrinology and Metabolism,Shanghai Yangpu Central Hospital,Yangpu Hospital of Tongji University,Shanghai 200090,China;Department of Endocrinology and Metabolism,Shanghai Minhang Hospital,Shanghai 201100,China;Department of Endocrinology and Metabolism,Shanghai Pudong Gongli Hospital,Shanghai 200135,China;Department of Endocrinology and Metabolism,Shanghai Traditional Chinese and Western Medicine Integrated Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200082,China;Department of Endocrinology and Metabolism,Shuguang Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200021,China;Department of Endocrinology and Metabolism,Tongren Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200336,China;Department of Endocrinology and Metabolism,Shanghai Third People's Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 201999,China;Department of Endocrinology and Metabolism,Shanghai Xuhui Hospital,Shanghai 200020,China;Department of Endocrinology and Metabolism,Xinhua Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200092,China;Department of Endocrinology and Metabolism,Huadong Hospital,Fudan University,Shanghai 200040,China;Department of Endocrinology and Metabolism,Shanghai Seventh People’s Hospital,Shanghai 200025,China;Department of Endocrinology and Metabolism,Dongfang Hospital,Tongji University,Shanghai 200120,China;Department of Endocrinology and Metabolism,Shanghai Pudong Punan Hospital,Shanghai 200125,China;Department of Endocrinology and Metabolism,Changhai Hospital,Shanghai 200433,China;Department of Endocrinology and Metabolism,Shanghai Qingpu Hospital,Qingpu Hospital of Zhongshan Hospital Affiliated to Fu

机构地区：[1]复旦大学附属中山医院内分泌科,上海200032 [2]上海市杨浦区中心医院同济大学附属杨浦医院内分泌科,上海200090 [3]上海市闵行区中心医院内分泌科,上海201100 [4]上海市浦东新区公利医院内分泌科,上海200135 [5]上海中医药大学附属上海市中西医结合医院内分泌科,上海200082 [6]上海中医药大学附属曙光医院内分泌科,上海200021 [7]上海交通大学医学院附属同仁医院内分泌科,上海200336 [8]上海交通大学医学院附属第三人民医院内分泌科,上海201999 [9]上海市徐汇区中心医院内分泌科,上海200020 [10]上海交通大学医学院附属新华医院内分泌科,上海200092 [11]复旦大学附属华东医院内分泌科,上海200040 [12]上海市第七人民医院内分泌科,上海200025 [13]上海市东方医院同济大学附属东方医院内分泌科,上海200120 [14]上海市浦东新区浦南医院内分泌科,上海200125 [15]上海长海医院内分泌科,上海200433 [16]复旦大学附属中山医院青浦分院上海市青浦区中心医院内分泌科,上海201799 [17]上海市普陀区中心医院内分泌科,上海200062 [18]上海市静安区市北医院内分泌科,上海200025

出　　处：《中华糖尿病杂志》2022年第6期555-562,共8页CHINESE JOURNAL OF DIABETES MELLITUS

摘　　要：目的通过24 h持续葡萄糖监测(CGM)技术,探究短期1.5 mg度拉糖肽周制剂治疗对2型糖尿病(T2DM)患者血糖波动及血糖控制的作用。方法研究采用多中心、前瞻性研究设计,共纳入149例T2DM患者,受试患者均接受度拉糖肽周制剂1.5 mg治疗2~4周,同时使用瞬感CGM设备监测患者动态血糖水平。研究分析的主要指标包括平均血糖波动幅度(MAGE)、日平均血糖(MDG)、葡萄糖在目标范围内时间(TIR)、高血糖时间(TAR)及低血糖时间(TBR),次要指标包括合并药物剂量变化、药物相关不良反应及血压变化情况。使用重复测量资料的混合效应模型(MEM)或配对Mann-Whitney秩和检验对治疗后每周的主要指标间差异进行分析。结果在接受1.5 mg度拉糖肽治疗4周后,受试患者的MDG水平和MAGE分别降低(0.76±0.31)和(0.50±0.13)mmol/L(均P<0.05)。治疗2周后患者每日TIR由治疗后首周内的73.91%(IQR为25.20%)升高至77.49%(IQR为24.89%),中位差异为3.58%(P<0.01),TAR(>10.0 mmol/L)则由首周内的2.95%(IQR为10.76%)降低至1.94%(IQR为7.24%),中位差异为1.01%(P<0.001),而TBR变化无统计学意义(P>0.05)。治疗1周后患者的收缩压较基线降低(5.2±1.5)mmHg(1 mmHg=0.133 kPa),差异有统计学意义(P<0.001)。有14例患者报告了可能的治疗相关不良事件,主要包括胃肠道反应和低血糖事件。结论在T2DM患者人群中,使用1.5 mg度拉糖肽周制剂治疗2~4周可显著降低患者的血糖波动、改善短期血糖控制指标并降低血压,同时不会显著增加患者发生低血糖事件的风险。Objective To investigate the effects of once-weekly dulaglutide 1.5 mg treatment on glucose variability and glucose control in type 2 diabetes patients using 24 h continuous glucose monitoring(CGM)technology.Methods A multi-center,prospective study was carried out.A total of 149 type 2 diabetes patients were recruited,who were treated with dulaglutide for 2 to 4 weeks,wearing CGM devices to monitor the glucose level.The primary evaluation indicators included mean amplitude of glycemic excursions(MAGE),mean daily glucose(MDG),time in target glucose range(TIR),time above range and time below range(TAR,TBR).Secondary indicators included change of concomitant medication dosages,treatment-related adverse events and change of blood pressure.Mixed effects model(MEM)of repeated measurement data or paired Mann-Whitney rank-sum test was used to analysis the differences between CGM parameters in each week during the treatment period.Results MDG and MAGE of patients decreased by(0.76±0.31)and(0.50±0.13)mmol/L(P<0.05),respectively,after the 4-week dulaglutide treatment.When compared with the first week,time in range(TIR)in week 2 increased from 73.91%(IQR 25.20%)to 7.49%(IQR 24.89%),and the mean difference was 3.58%(P<0.01).Time in hyperglycemia decreased from 2.95%(IQR 10.76%)to 1.94%(IQR 7.24%),and the median difference was 1.01%(P<0.001),while the time in hypoglycemia did not change(P>0.05).Mean systolic pressure of patients decreased by(5.2±1.5)mmHg(1 mmHg=0.133 kPa)after the first-week treatment.Furthermore,14 patients reported treatment-related adverse events including gastrointestinal reaction and hypoglycemia.Conclusions Treatment with dulaglutide 1.5 mg weekly for 2 to 4 weeks could significantly reduce glycemic variability,improve short-term glucose control and lower blood pressure in type 2 diabetes patients without significantly increasing the risk of hypoglycemic events.

关 键 词：糖尿病 2型 度拉糖肽 血糖波动 前瞻性研究 

分 类 号：R587.1[医药卫生—内分泌]