Ding Lu, Sun Bang, Xiao Xinhua
Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Diabetes Research Center of Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
Int J Endocrinol. 2020 Sep 28;2020:1626484. doi: 10.1155/2020/1626484. eCollection 2020.
To conduct the first meta-analysis of randomized controlled trials (RCTs) comparing glucagon-like peptide 1 receptor agonists (GLP-1RAs) with sodium-glucose cotransporter 2 inhibitors (SGLT-2is) for obese type 2 diabetes (T2D) patients uncontrolled on metformin.
We searched Pubmed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Ovid, and Web of Science from inception to May 14, 2020, without language restrictions for eligible RCTs. The primary outcome is the mean change from baseline in glycated haemoglobin (HbA1c).
Totally, 3 RCTs enrolled 2066 patients were identified. Compared with SGLT-2is, treatment with GLP-1RAs achieved significant reduced HbA1c by 0.40% (95% CI: -0.54, -0.25; < 0.00001), fasting blood glucose (FBG) by 0.17 mmol/L (95% CI: -0.31, -0.04; =0.01), and postprandial blood glucose (PBG) by 0.32 mmol/L (95% CI: -0.49, -0.14; =0.0003) for obese T2D patients uncontrolled on metformin. The significant benefit of weight loss was seen in semaglutide (MD: -0.75; 95% CI: -1.18, -0.31; < 0.0007). No significant difference was detected between GLP-1RAs and SGLT-2is in overall adverse events (RR: 1.03; 95% CI: 0.98, 1.09; =0.76), but gastrointestinal events showed higher occurrence in GLP-1RAs groups compared with SGLT-2is (RR: 1.62; 95% CI: 1.37, 1.93; < 0.00001). Subgroup analyses revealed that follow-up time did not statistically influence glycemic control.
GLP-1RAs are superior to SGLT-2is for obese T2D patients uncontrolled on metformin in glycemic control without an increase in adverse events except for a higher occurrence in gastrointestinal events. Future large longer-term follow-up clinical trials are needed to provide more evidence about the sustainable effects and safety of GLP-1RAs compared with SGLT-2is.
开展首项比较胰高血糖素样肽1受体激动剂（GLP-1RAs）与钠-葡萄糖协同转运蛋白2抑制剂（SGLT-2is）对二甲双胍治疗未达控制的肥胖2型糖尿病（T2D）患者疗效的随机对照试验（RCT）的荟萃分析。
检索了PubMed、Embase、Cochrane对照试验中心注册库（CENTRAL）、Ovid和Web of Science，检索时间从建库至2020年5月14日，纳入的RCT不受语言限制。主要结局是糖化血红蛋白（HbA1c）较基线的平均变化。
共纳入3项RCT，涉及2066例患者。与SGLT-2is相比，对于二甲双胍治疗未达控制的肥胖T2D患者，使用GLP-1RAs治疗可使HbA1c显著降低0.40%（95%CI：-0.54，-0.25；P<0.00001），空腹血糖（FBG）降低0.17 mmol/L（95%CI：-0.31，-0.04；P=0.01），餐后血糖（PBG）降低0.32 mmol/L（95%CI：-0.49，-0.14；P=0.0003）。司美格鲁肽有显著的减重益处（MD：-0.75；95%CI：-1.18，-0.31；P<0.0007）。GLP-1RAs与SGLT-2is在总体不良事件方面未检测到显著差异（RR：1.03；95%CI：0.98，1.09；P=0.76），但GLP-1RAs组胃肠道事件的发生率高于SGLT-2is组（RR：1.62；95%CI：1.37，1.93；P<0.00001）。亚组分析显示随访时间对血糖控制无统计学影响。
对于二甲双胍治疗未达控制的肥胖T2D患者，GLP-1RAs在血糖控制方面优于SGLT-2is，且不良事件未增加，除了胃肠道事件发生率较高。未来需要开展更多大型长期随访临床试验，以提供更多关于GLP-1RAs与SGLT-2is相比的持续疗效和安全性的证据。
