单用二甲双胍控制不佳的2型糖尿病患者分别联用利拉鲁肽与甘精胰岛素26周的疗效及安全性比较

Efficacy and safety of liraglutide compared with insulin glargine in patients with type 2 diabetes mellitus inadequately controlled with metformin

目的 观察比较单用二甲双胍血糖控制不佳的2型糖尿病患者分别联用人胰升糖素样肽1类似物利拉鲁肽与甘精胰岛素的有效性和安全性.方法 纳入90例单用二甲双胍（≥1500 mg/d,疗程≥3个月）后血糖控制不理想（HbA1C7.5％ ～ 10.0％）的2型糖尿病患者（年龄18 ～79岁）.受试者保持初始的二甲双胍口服降糖方案不变,按1∶1的比例随机分配到联用利拉鲁肽组或甘精胰岛素组治疗,利拉鲁肽起始0.6 mg每日1次皮下注射,1周后加至1.2 mg;甘精胰岛素起始剂量为0.1～0.2 U/kg,每周电话随访2次,根据每次随访前连续3d早餐前末梢血糖浓度采用固定胰岛素滴定法则调整剂量.分别于基线及治疗后第4、12、20、26周检测HbA1C、血糖谱、体重、血压和血脂谱等指标.最终86例完成试验.结果 26周后,利拉鲁肽组HbA1C的均值及HbA1C ＜7％的达标率与甘精胰岛素组相当[分别为（7.06±0.87）％对（7.25±1.20）％,47.73％对45.23％,P＞0.05],但利拉鲁肽组复合终点（HbA1C ＜7％且无低血糖发生及无体重增加）达标率更高（P＜0.05）.甘精胰岛素组空腹血糖均值低于利拉鲁肽组,利拉鲁肽组餐后2h血糖均值低于甘精胰岛素组（P＜0.05或P＜0.01）.利拉鲁肽组体重、腰围、体重指数分别较基线下降（3.21±1.18）kg、（3.82± 1.21）cm、（1.95±0.61） kg/m2（P＜0.01或P＜0.05）,甘精胰岛素组分别较基线增加（2.86±0.43） kg、（1.52±0.56） cm、（0.61 ±0.25） kg/m2（均P＜0.05）.利拉鲁肽组收缩压、甘油三酯均较基线显著降低（P＜0.01或P＜0.05）;2组均无严重不良反应,利拉鲁肽组较甘精胰岛素组轻度低血糖发生率低（4.55％对21.43％,P＜0.05）.结论 利拉鲁肽在单用二甲双胍控制不佳的患者中与甘精胰岛素的降糖疗效相当,且具有减轻体重、降低收缩压、改善血脂等降糖外优势,安全性及耐受性良好,对二甲双胍血糖控制不佳后的2型糖尿病患者不失为一种良好的选择.

Objective To observe the effect and safety of the human glucagon-like peptide-1 analogue,liraglutide,versus insulin glargine in patients with type 2 diabetes mellitus inadequately controlled with metformin alone.Method Ninty patients with type 2 diabetes mellitus（aged 18-79 years,HbA1C 7.5％-10.0％,body mass index＜40 kg/m2） who had inadequate glycaemic control on metformin were allocated for the research with an open,randomized,parallel controlled clinical research method.The patients kept the original dose of metformin unchanged and were randomly assigned to the liraglutide group or the insulin glargine group according to a proportion of 1 ∶ 1.Liraglutide group started with a dose of 0.6 mg subcutaneous injection qd,changed to 1.2 mg subcutaneous injection qd after one week and kept unchanged until the end of the research.Insulin glargine group started with a dose of 0.1-0.2 U/kg according to the fingertips peripheral blood glucose level before breakfast on the continuous 3 d before every follow-up.At the baseline,after 4 weeks,12 weeks,20 weeks,and 26 weeks of treatment,HbA1C,blood glucose,lipids weight,blood pressure were arranged to measured.86 patients finally completed the study.Results Mean HbA1C and the success rate of HbA1C ＜7％ were similar between liraglutide group and insulin glargine group [（7.06 ± 0.87） ％ vs （7.25 ± 1.20） ％,47.73 ％ vs 45.23 ％,P＞0.05],while the percentage of subjects reaching the composite endpoint of HbA1C＜7％ with no hypoglycemia and no weight gain was significantly higher in liraglutide group than insulin group（P＜0.05） ; Fasting plasma glucose decreased more markedly in insulin glargine group,2 h postprandial plasma glucose was decreased more markedly in liraglutide group（P＜0.05 or P＜0.01）.Liraglutide significantly reduced mean body weight by （3.21 ± 1.18） kg,waist circumference by （3.82 ± 1.21） cm,and body mass index by （1.95 ± 0.61） kg/m2 （P＜0.01 or P＜0.05）,while in the insulin glargine group there sere rise of respective figure of（2.86 ± 0.43） kg,（1.52 ± 0.56） cm,and （0.61 ± 0.25） kg/m2 （P＜0.05）,systolic blood pressure and serum triglyceride declined.There was no serious adverse affect in both groups,the incidence of mild hypoglycemia was significantly less in liraglutide group and has a statistically significant difference （4.55％ vs 21.43％,P＜0.05）.Conclusions Liraglutide showed a good effect on reducing weight,systolic blood pressure,blood lipid and in addition to blood glucose control which is comparable to insulin glargine.What is more,liraglutide had good safety and tolerability,which can be regarded as a good choice for patients with type 2 diabetes mellitus inadequately controlled with metformin alone.