利拉鲁肽联合胰岛素治疗成人2型糖尿病文献的疗效及安全性评估

Assessment the Efficacy and Safety of Liraglutide Combined with Insulin in the Treatment of Adult Type 2 Diabetes Mellitus

目的:评估利拉鲁肽联用胰岛素的疗效与安全性。方法:检索CNKI、万方数据、PubMed、cochrane library等数据库收集有关利拉鲁肽联用预混胰岛素、每日多次胰岛素注射(MDI)、胰岛素皮下持续输注(CSII)等文献,评估糖化血红蛋白(HbAlc)变化值、空腹血糖(FPG)、餐后2h血糖(2h-PPG)、体质指数(BMI)变化值、体质量(BW)变化值和日胰岛素总用量等疗效指标;低血糖发生情况、严重低血糖事件发生情况以及胃肠道不良反应事件发生情况等安全性指标。结果:利拉鲁肽联用胰岛素(MDI、预混、CSII)较单用胰岛素相比,降低BW、改善HbA1c、减少日胰岛素总用量优势显著,HbA1c<7%达标率更高对FPG、2h-PPG控制效果更好或相当。利拉鲁肽组均未见严重低血糖事件发生然而胃肠道不良反应较为明显,但多较轻微且能耐受并在4周内逐渐缓解。结论:利拉鲁肽与预混胰岛素联用未显著增加低血糖发生率,临床获益风险相对明显,而利拉鲁肽联合MDI或CSII研究较少,低血糖风险可能更高,但尚缺乏系统性评价、Meta分析等高质量证据支持,与其他胰岛素联用后期还需开展多中心、大样本随机双盲对照试验或真实世界研究,为临床用药提供可靠依据。

Objective:To evaluate the efficacy and safety of liraglutide combined with insulin.Methods:The related literatures about the efficacy and safety of liraglutide combined with premixed insulin were searched,and multiple daily insulin injections(MDI)and continuous subcutaneous insulin infusion(CSII)in the treatment of adult type 2 diabetes mellitus were reviewed in CNKI,Wan Fang,Pubmed and the Cochrane library databases.The outcome indicators for efficacy included glycosylated hemoglobin(HbAlC)changes in value,the ratio of HbAlC<7%,fasting plasma glucose(FPG),2 h postprandial blood glucose(2 h-PPG),body mass index(BMI)changes in value,changes in body weight(BW)and total daily insulin dosage,etc.The safety indicators included occurrence of hypoglycemia,occurrence of severe hypoglycemia events and occurrence of overall adverse events.Results:Compared with insulin alone,liraglutide combined with basal-prandial insulin(MDI,premixed or CSII)had more significant weight loss and total daily insulin dosage reduction.The efficacy,HbAlC%changes in value,ratio of HbAlC<7%,FPG,2 h-PPG,BMI and BW changes in value were also better or similar.No severe hypoglycemia events occurred in liraglutide group with each combined regimen,and gastrointestinal adverse reactions were more common,while most of them were mild,tolerable and gradually relieved within 4 weeks.Conclusion:Liraglutide combined with premixed insulin did not significantly increase the risk of hypoglycemia,and the clinical benefits maybe greater than the risks.While few studies have been conducted on liraglutide in combination with MDI or CSII,the risk of hypoglycemia may be higher,while highly quality evidences are lack,such as systematic reviews and Meta analysis,to support the guess.The efficacy and safety of liraglutide combined with insulin still need to be confirmed by carrying out multi-center randomized double-blind controlled trials and real world research to provide reliable evidences for clinicians.