胰高血糖素样肽1受体激动剂治疗合并超重或肥胖的2型糖尿病的疗效和安全性的Meta分析

Efficacy and safety of glucagon-like peptide 1 receptor agonists in the treatment of overweight or obese patients with type 2 diabetes:a Meta-analysis

目的系统评价胰高血糖素样肽1受体激动剂(GLP-1RA)治疗合并超重或肥胖2型糖尿病(T2DM)患者的有效性与安全性。方法计算机检索PubMed、Embase、Cochrane Library、Ovid、ClinicalTrial.gov、SinoMed、CNKI、WanFang Data和VIP数据库,搜集有关GLP-1RA治疗T2DM合并超重或肥胖患者的随机对照试验(RCT),检索时限均从2005年1月1日至2023年11月1日。由2位研究者独立筛选文献、提取资料并评价纳入研究的偏倚风险后,采用R软件进行Meta分析,并采用GRADE系统进行证据质量评价。结果共纳入71个RCT,包括29476例患者。Meta分析结果显示,相比于其他降糖药,GLP-1RA在改善糖化血红蛋白[WMD=-0.55,95%CI(-0.65,-0.45),P<0.001]、减重[WMD=-2.61,95%CI(-3.25,-1.97),P<0.001]方面均具有优势;GLP-1RA对空腹血糖的改善效果呈时间依赖性[16周以内:WMD=0.25,95%CI(-0.17,0.66),P=0.250;16~52周:WMD=-0.06,95%CI(-0.32,0.20),P=0.650;>52~104周:WMD=-1.67,95%CI(-1.91,-1.43),P<0.001];安全性方面,GLP-1RA的总体不良反应发生率较高[RR=1.11,95%CI(1.07,1.15),P<0.001];但低血糖发生率低于胰岛素[RR=0.58,95%CI(0.48,0.71),P<0.001],而与口服降糖药的差异无统计学意义[RR=0.83,95%CI(0.58,1.19),P=0.310]。GRADE系统评价显示,仅低血糖发生率的证据等级为中等,其余结局指标的证据水平均为低级。结论当前证据显示,对于T2DM合并肥胖或超重患者,GLP-1RA尤其是司美格鲁肽相比于安慰剂、胰岛素或口服降糖药,能更有效兼顾降糖和减重,虽总体不良反应较多,但可减少低血糖发生。

Objective To evaluate the efficacy and safety of glucagon-like peptide 1 receptor agonists(GLP-1RA)in type 2 diabetes mellitus(T2DM)patients with overweight or obese.Methods PubMed,Embase,Cochrane Library,Ovid,ClinicalTrial.gov,SinoMed,CNKI,WanFang Data and VIP databases were electronically searched to collect randomized controlled trials(RCTs)on the efficacy of GLP-1RA in the treatment of T2DM patients with overweight or obese from January 1,2005 to November 1,2023.Two researchers independently screened the literature,extracted data and evaluated the risk of bias of the included studies.R software was then used for meta-analysis.The level of evidence was assessed by using the GRADE system.Results A total of 71 RCTs were included,including 29476 patients.The results of Meta-analysis showed that compared with other hypoglycemic drugs,GLP-1RA showed superior effects in improving HbA1c status(WMD=-0.55,95%CI-0.65 to-0.45,P<0.001)and weight loss(WMD=-2.61,95%CI-3.25 to-1.97,P<0.001),while the effect on fasting plasm glucose was time-dependent(within 16 weeks:WMD=0.25,95%CI-0.17 to 0.66,P=0.250;16 to 52 weeks:WMD=-0.06,95%CI-0.32 to 0.20,P=0.650;over 52 to 104 weeks:WMD=-1.67,95%CI-1.91 to-1.43,P<0.001).In terms of safety,the incidence of GLP-1RA’s adverse reactions was higher than other hypoglycemic drugs(RR=1.11,95%CI 1.07 to 1.15,P<0.001);the incidence of hypoglycemia was lower with GLP-1RA than with insulin(RR=0.58,95%CI 0.48 to 0.71,P<0.001)and similar to oral hypoglycemic drugs(RR=0.83,95%CI 0.58 to 1.19,P=0.310).According to the GRADE assessment,only the certainty of the evidence for the results of the incidence of hypoglycemia was moderate,and the certainty of the evidence for the other results was low.Conclusion Current evidence shows that for T2DM patients with overweight or obese,GLP-1RA especially semaglutide,was more effective in lowering blood glucose,controlling body weight and reducing the occurrence of hypoglycemia than placebo,insulin and oral hypoglycemic drugs.