雷诺嗪治疗2型糖尿病的疗效与安全性的Meta分析

Efficacy and safety of ranolazine in the treatment of type 2 diabetes mellitus:a Meta-analysis

目的:系统评价雷诺嗪治疗2型糖尿病(diabetes mellitus type 2,T2DM)的疗效与安全性。方法:全面检索CENTRAL、Medline、Embase、CNKI、VIP、CBM、Wanfang数据库,以及WHO临床试验注册平台和美国临床试验注册平台,对检索到的随机对照试验(randomized controlled trial,RCT)按Cochrane系统评价方法进行质量评价,并用Rev Man 5.2软件进行Meta分析。结果:共纳入7个RCTs,3 131例患者。Meta分析显示:雷诺嗪(1 000 mg bid)单药治疗与安慰剂相比可降低糖化血红蛋白(glycosylated hemoglobin,Hb A1c)(MD=-0.55,95%CI=-0.73^-0.37,P=0.000),空腹血糖(fasting plasma glucose,FPG)(SMD=-0.19,95%CI=-0.37^-0.01,P=0.04),餐后2 h血糖(postprandial 2 hours blood glucose,2h PG)(SMD=-0.34,95%CI=-0.53^-0.15,P=0.0005)。在降糖药治疗基础上,雷诺嗪(1 000 mg bid)与安慰剂相比可降低Hb A1c(MD=-0.47,95%CI=-0.62^-0.32,P=0.000),两组降低FPG(SMD=-0.00,95%CI=-0.21~0.20,P=0.97)及2h PG(SMD=-0.12,95%CI=-0.33~0.09,P=0.28)的作用相当;雷诺嗪(750 mg bid)与安慰剂相比可降低Hb A1c(MD=-0.48,95%CI=-0.85^-0.11,P=0.01),两组降低FPG(SMD=0.11,95%CI=-0.26~0.48,P=0.57)的作用相当;雷诺嗪(500 mg bid)与曲美他嗪相比降低Hb A1c(MD=-0.30,95%CI=-1.35~0.75,P=0.58),FPG(SMD=-0.36,95%CI=-0.94~0.22,P=0.22)及2h PG(SMD=0.15,95%CI=-0.42^-0.73,P=0.60)的作用相当。雷诺嗪不增加低血糖风险(RR=1.24,95%CI=0.80~1.93,P=0.34)。结论:雷诺嗪对T2DM患者有一定降低Hb A1c水平作用且安全性良好,其降糖机制与抑制胰高血糖素释放有关。

Objective ：To evaluate the efficacy and safety of ranolazine in the treatment of diabetes mellitus type 2 （T2DM）. Methods： CENTRAL, Medline, EMbase, CNKI, VIP, CBM, Wanfang database, WHO Clinical Trials Registry Platform and ClinicalTrials.gov were searched. The quality of included randomized controlled trials was assessed according to the Cochrane Collaboration system review, and then Meta-analysis was performed using RevMan 5.2. Results：A total of 7 randomized controlled trials （RCTs） were enrolled in- cluding 3 131 patients. Meta-analysis showed that ranolazine（ 1 000 mg bid） monotherapy compared with placebo resulted in a signif- icant reduction in HbA1c（MD=-0.55,95%CI=-0.73 to -0.37,P=0.000）,in FPG（SMD=-0.19,95%CI=-0.37 to -0.01,P=0.04）,in 2hPG （SMD=-0.34,95%CI=-0.53 to -0.15, P=0.000 5）. As an add-on interaction with antidiabetes compared with placebo, ranolazine（ 1 000 mR bid）resulted in a significant reduction in glycosylated hemoglobin（HbAlc）（MD=-0.47,95%CI=-0.62 to -0.32,P=0.000） ,a similar reduction in fasting blood-glucose（FPG） （SMD=-0.00,95%CI=-0.21 to 0.20, P--0.97）, in postprandial 2 hours blood glucose （2hPG） （SMD=-0. 12,95%CI=-0.33 to 0.09, P=0.28）, ranolazine （750 mg bid） resulted in a significant reduction in HbAlc （MD=-0.48,95%CI=-0.85 to -0.l 1, P=0.01 ）, a similar reduction in FPG（SMD=0. 11,95%CI=-0.26 to 0.48 ,P=0.57）. When add-on to antidiabetes ranolazine （500 mg bid） compared with trimetazidine elicited a similar reduction in HbAle（MD=-0.30,95%CI=-l.35 to 0.75,P=0.58）,in FPG（SMD=-0.36,95%CI=-0.94 to 0.22,P=0.22）, in 2hPG（SMD=O.15,95%CI=-0.42 to -0.73 ,P=0.60）. Ranolazine didn＇t increase the risk of hypoglycemia（RR=l.24, 95%CI=0.80 to 1.93 ,P=0.34）. Conclusion：Ranolazine can effectively reduce HbAlc level by inhibiting glucagon secretion and safe for adults with T2DM.