Abstract：
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are new drugs for the treatment of obesity.
To assess the weight-loss effects of GLP-1RAs in the treatment of patients with overweight or obesity without diabetes.
This is a systematic review with meta-analysis and trial sequential analysis. PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched from their inception to January 1, 2022. Eligible trials report on outcomes including body weight (BW), body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), or total body fat (TBF). Mean differences (MDs) and standardized mean differences (SMDs) were summarized using random-effects models.
Forty-one trials involving 15,135 participants were included. Compared with controls, GLP-1RAs significantly reduced BW (MD -5.319 kg, 95% CI: -6.465, -4.174), BMI (MD -2.373 kg/m2, 95% CI: -2.821, -1.924), WC (MD -4.302 cm, CI:-5.185 to -3.419), WHR (MD -0.011, CI -0.015 to -0.007), but not TBF (MD -0.320%, CI -1.420 to -0.780). Trial sequential analysis (TSA) supported conclusive evidence of the effects of GLP-1RAs on BW, BMI, and WC for weight loss. GLP-1RAs had nonlinear dose-response relationships with weight loss. Extensive sensitivity analyses demonstrated the robustness of the results, though the GRADE certainty of the evidence ranged from high to very low. High to moderate GRADE certainty of evidence suggested semaglutide as the most effective GLP-1RA agent, with the best efficacy and low to moderate risk of adverse effects.
The present study provides conclusive evidence for the effect of GLP-1RAs on weight loss in a nonlinear dose-response manner in patients with obesity or overweight without diabetes. In terms of changes in BW, BMI, and WC, there is firm evidence for the overall weight-loss effects of GLP-1RAs. Of the GLP-1RAs, semaglutide might be the most effective agent.
To assess the weight-loss effects of GLP-1RAs in the treatment of patients with overweight or obesity without diabetes.
This is a systematic review with meta-analysis and trial sequential analysis. PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched from their inception to January 1, 2022. Eligible trials report on outcomes including body weight (BW), body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), or total body fat (TBF). Mean differences (MDs) and standardized mean differences (SMDs) were summarized using random-effects models.
Forty-one trials involving 15,135 participants were included. Compared with controls, GLP-1RAs significantly reduced BW (MD -5.319 kg, 95% CI: -6.465, -4.174), BMI (MD -2.373 kg/m2, 95% CI: -2.821, -1.924), WC (MD -4.302 cm, CI:-5.185 to -3.419), WHR (MD -0.011, CI -0.015 to -0.007), but not TBF (MD -0.320%, CI -1.420 to -0.780). Trial sequential analysis (TSA) supported conclusive evidence of the effects of GLP-1RAs on BW, BMI, and WC for weight loss. GLP-1RAs had nonlinear dose-response relationships with weight loss. Extensive sensitivity analyses demonstrated the robustness of the results, though the GRADE certainty of the evidence ranged from high to very low. High to moderate GRADE certainty of evidence suggested semaglutide as the most effective GLP-1RA agent, with the best efficacy and low to moderate risk of adverse effects.
The present study provides conclusive evidence for the effect of GLP-1RAs on weight loss in a nonlinear dose-response manner in patients with obesity or overweight without diabetes. In terms of changes in BW, BMI, and WC, there is firm evidence for the overall weight-loss effects of GLP-1RAs. Of the GLP-1RAs, semaglutide might be the most effective agent.
摘要：
背景：胰高血糖素样肽-1受体激动剂（GLP-1RAs）是治疗肥胖的新药。
目的：评估GLP-1RAs对超重或肥胖无糖尿病患者的减肥效果。
方法：这是一项系统综述，包括荟萃分析和试验序贯分析。PubMed,Embase,从开始到2022年1月1日，搜索了Cochrane中央控制试验登记册。合格的试验报告结果，包括体重（BW），体重指数（BMI），腰围（WC），腰臀比（WHR），或全身脂肪（TBF）。使用随机效应模型总结了平均差（MD）和标准化平均差（SMD）。
结果：纳入了41项试验，涉及15,135名参与者。与对照组相比，GLP-1RAs显着降低BW（MD-5.319kg，95%CI：-6.465，-4.174），BMI（MD-2.373kg/m2，95%CI：-2.821，-1.924），WC(MD-4.302cm,CI：-5.185至-3.419），WHR（MD-0.011，CI-0.015至-0.007），但不是TBF(MD-0.320%，CI-1.420至-0.780）。试验序贯分析（TSA）支持GLP-1RA对BW，BMI,和WC减肥。GLP-1RA与体重减轻具有非线性剂量反应关系。广泛的敏感性分析证明了结果的稳健性，尽管证据的等级确定性从高到非常低。证据的高至中度确定性表明司马鲁肽是最有效的GLP-1RA药物，具有最佳疗效和低至中度的不良反应风险。
结论：本研究提供了确凿证据证明GLP-1RAs对肥胖或超重无糖尿病患者体重下降的非线性剂量反应方式的影响。就BW的变化而言，BMI,WC,有确凿的证据表明GLP-1RA的总体减肥效果。在GLP-1RA中，司马鲁肽可能是最有效的药物。
目的：评估GLP-1RAs对超重或肥胖无糖尿病患者的减肥效果。
方法：这是一项系统综述，包括荟萃分析和试验序贯分析。PubMed,Embase,从开始到2022年1月1日，搜索了Cochrane中央控制试验登记册。合格的试验报告结果，包括体重（BW），体重指数（BMI），腰围（WC），腰臀比（WHR），或全身脂肪（TBF）。使用随机效应模型总结了平均差（MD）和标准化平均差（SMD）。
结果：纳入了41项试验，涉及15,135名参与者。与对照组相比，GLP-1RAs显着降低BW（MD-5.319kg，95%CI：-6.465，-4.174），BMI（MD-2.373kg/m2，95%CI：-2.821，-1.924），WC(MD-4.302cm,CI：-5.185至-3.419），WHR（MD-0.011，CI-0.015至-0.007），但不是TBF(MD-0.320%，CI-1.420至-0.780）。试验序贯分析（TSA）支持GLP-1RA对BW，BMI,和WC减肥。GLP-1RA与体重减轻具有非线性剂量反应关系。广泛的敏感性分析证明了结果的稳健性，尽管证据的等级确定性从高到非常低。证据的高至中度确定性表明司马鲁肽是最有效的GLP-1RA药物，具有最佳疗效和低至中度的不良反应风险。
结论：本研究提供了确凿证据证明GLP-1RAs对肥胖或超重无糖尿病患者体重下降的非线性剂量反应方式的影响。就BW的变化而言，BMI,WC,有确凿的证据表明GLP-1RA的总体减肥效果。在GLP-1RA中，司马鲁肽可能是最有效的药物。
