那格列奈联合二甲双胍对比单用那格列奈治疗2型糖尿病疗效和安全性的Meta分析

Efficacy and Safety of Nateglinide Combined with Metformin versus Nateglinide Alone for Type 2 Diabetes Mellitus:A Meta-analysis

目的:系统评价那格列奈联合二甲双胍对比单用那格列奈治疗2型糖尿病(T2DM)的疗效和安全性,以为临床提供循证参考。方法:计算机检索PubMed、EMBase、Medline、Cochrane Library、中国期刊全文数据库、维普数据库和万方数据库,收集那格列奈联合二甲双胍(试验组)与单用那格列奈(对照组)比较治疗T2DM的随机对照试验(RCT)。由两位评价员按照纳入与排除标准独立筛选文献、提取资料,根据Cochrane Handbook 5.1.0评价纳入研究的质量,并采用Cochrane协作网提供的Rev Man 5.2统计软件进行Meta分析。结果:共纳入7项RCT,合计1 188例患者。Meta分析结果显示,试验组患者空腹血糖[MD=-0.87,95%CI(-1.64,-0.11),P=0.03]、餐后2 h血糖[MD=-0.66,95%CI(-1.20,-0.11),P=0.02]、甘油三酯[MD=-0.11,95%CI(-0.13,-0.09),P<0.000]均显著低于对照组,总胆固醇[MD=0.11,95%CI(0.09,0.13),P<0.000]、低密度脂蛋白[MD=0.10,95%CI(0.01,0.20),P=0.04]、低血糖发生率[OR=2.41,95%CI(1.66,3.52),P<0.000]、胃肠道不良反应发生率[OR=2.51,95%CI(1.55,4.06),P<0.000]均显著高于对照组,而两组患者糖化血红蛋白[MD=0.01,95%CI(-0.35,0.38),P=0.94]、血压[收缩压:MD=8.80,95%CI(-0.87,18.48),P=0.07;舒张压:MD=8.67,95%CI(-3.02,20.36),P=0.15]、高密度脂蛋白[MD=-0.00,95%CI(-0.01,0.01),P=0.98]比较差异无统计学意义。结论:那格列奈联合二甲双胍治疗T2DM患者,在控制血糖、降低甘油三酯方面优于单用那格列奈,但低血糖和胃肠道不良反应发生率较高。由于纳入研究样本量较小、质量不高,该结论仍需更多大样本、多中心、高质量的RCT进一步验证。

OBJECTIVE： To evaluate the efficacy and safety of nateglinide combined with metformin versus nateglinide alone for type 2 diabetes mellitus （T2DM） , and to provide evidence-based reference for the clinic, METHODS： Retrieved from PubMed, EMBase, Medline, Cochrane Library, CNK1, VIP and Wanfang database, RCT about nateglinide combined with metfor- rain （trial group） and nateglinide alone （control group） in the treatment of T2DM were collected. The data were extracted accord- ing to the inclusion and exclusion criteria by two researchers independently, and the quality of included studies was assessed accord- ing to the Cochrane Handbook 5.1.0. Meta-analysis was conducted by using Cochrane network Rev Man 5.2 software. RESULTS： A total of 7 RCT included, involving 1 188 patients. Meta-analysis showed that FPG [MD= - 0.87,95 % CI （ - 1.64 , - 0.11 ）, P= 0.03], 2 hPG [MD： -- 0.66,95 % CI （ - 1.20, - 0.11 ）, P= 0.02] and TG [MD=- 0.11,95 % CI （ - 0.13, - 0.09 ）, P〈 0.000] of trial group were significantly lower than those of control group; TC [MD： 0.11,95 % CI （0.09, 0.13）, P〈：0.000], LDL-C [MD = 0.10, 95%CI（0.01,0.20） ,P=0.04], hypoglycemia [OR：2.41,95%CI（1.66,3.52） ,P〈0.000] and gastrointestinal discomfort [OR=2.51, 95% CI （1.55,4.06）, P〈0.000] of trial group were significantly higher than those of control group; there was no statistical signifi- cance in HbA1c [MD=0.01,95% CI（ - 0.35,0.38）, P：0.94] , blood pressure [SBP： MD=8.80,95% CI （ - 0.87, 18.48）, P=0.07 ; DBP： MD = 8.67,95 % CI （ - 3.02,20.36 ）, P= 0.15] and HDL-C [MD =- 0.00,95 % CI （ -0.01,0.01 ）, P = 0.98]. CONCLUSIONS ： Nateglinide combined with metformin is better than nateglinide alone in blood glucose control and the decrease of TG in T2DM pa- tients, but result in the high incidence of hypoglycemia and gastrointestinal discomfort.