Department of Pharmacy, The Third Affiliated Hospital (The Affiliated Luohu Hospital) of Shenzhen University, Shenzhen, Guangdong Province 518001, China.
Department of Pharmacy, The Third Affiliated Hospital (The Affiliated Luohu Hospital) of Shenzhen University, Shenzhen, Guangdong Province 518001, China.
Metabolism. 2024 Dec;161:156038. doi: 10.1016/j.metabol.2024.156038. Epub 2024 Sep 19.
This study aimed to provide evidence-based support and a reference for the efficacy and safety of seven glucagon-like peptide-1 (GLP-1) receptor agonists and polyagonists for weight loss in patients with obesity or overweight through a network meta-analysis.
Relevant randomized controlled trials (RCTs) with an intervention duration of at least 16 weeks assessing seven GLP-1 receptor agonists and polyagonists (mazdutide, 6 or 4.5 mg; retatrutide, 12 or 8 mg; tirzepatide, 15 or 10 mg; liraglutide, 3.0 mg; semaglutide, 2.4 mg; orforglipron, 45 or 36 mg; and beinaglutide, 0.2 mg) in patient with obesity or overweight was searched using three databases (Cochrane Library, PubMed, and Embase) from creation to August 30, 2024. The primary outcome was the percentage change in body weight from baseline. Secondary outcomes included changes in waist circumference, hemoglobin A1c, and fasting plasma glucose level from baseline; adverse events, serious adverse events, adverse event withdrawal, and hypoglycemic events. We conducted a frequentist random-effects network meta-analysis to analyze the data extracted from the RCTs using Stata 16.1 software.
Twenty-seven RCTs of seven GLP-1 receptor agonists and polyagonists and 15,584 patients were included in the network meta-analysis. In terms of efficacy, compared with placebo, retatrutide 12 mg (-22.10 % in body weight and - 17.00 cm in waist circumference), retatrutide 8 mg (-20.70 % and - 15.90 cm), and tirzepatide 15 mg (-16.53 % and - 13.23 cm) were the three most efficacious treatments for reducing body weight and waist circumference. However, these treatments were less effective in patients with type 2 diabetes mellitus (T2DM). In addition, patients with a high body mass index (BMI) or longer treatment cycles exhibited significantly greater weight loss than those with a low BMI or shorter treatment cycles. In terms of safety, patients without T2DM had a higher incidence of adverse events than those with T2DM. None of the interventions increased the incidence of serious adverse or hypoglycemic events (˂54 mg/dL). There was no significant difference in the incidence of adverse event withdrawal for all interventions in head-to-head comparisons. In addition, disparities in race, BMI, and treatment cycles did not significantly increase the incidence of adverse events. Finally, the sensitivity and publication bias analyses indicated that the basic analysis results were reliable.
Retatrutide (both doses) and tirzepatide exhibited superior efficacy compared to other GLP-1 receptor agonists and polyagonists in reducing body weight and waist circumference. Patients without T2DM, those with a high BMI, and individuals undergoing longer treatment cycles demonstrated significantly greater weight loss and reductions in waist circumference. Dual or triple receptor agonists (GLP-1 plus glucose-dependent insulinotropic polypeptide and/or Glucagon receptor) are more effective for weight loss than GLP-1 receptor agonists.
通过网络荟萃分析，为 7 种胰高血糖素样肽-1（GLP-1）受体激动剂和多激动剂在肥胖或超重患者中的减肥疗效和安全性提供循证支持和参考。
检索 Cochrane 图书馆、PubMed 和 Embase 数据库，检索时间为创建至 2024 年 8 月 30 日，纳入评估 7 种 GLP-1 受体激动剂和多激动剂（mazdutide，6 或 4.5mg；retatrutide，12 或 8mg；tirzepatide，15 或 10mg；liraglutide，3.0mg；semaglutide，2.4mg；orforglipron，45 或 36mg；和 beinaglutide，0.2mg）治疗肥胖或超重患者的至少 16 周干预的随机对照试验（RCT）。主要结局是体重从基线的百分比变化。次要结局包括体重、腰围、血红蛋白 A1c 和空腹血糖水平从基线的变化；不良事件、严重不良事件、不良事件停药和低血糖事件。我们使用 Stata 16.1 软件对从 RCTs 中提取的数据进行了似然随机效应网络荟萃分析。
纳入了 27 项 GLP-1 受体激动剂和多激动剂的 7 项 RCT 和 15584 名患者的网络荟萃分析。在疗效方面，与安慰剂相比，retatrutide 12mg（体重下降-22.10%，腰围减少-17.00cm）、retatrutide 8mg（体重下降-20.70%，腰围减少-15.90cm）和 tirzepatide 15mg（体重下降-16.53%，腰围减少-13.23cm）是三种降低体重和腰围最有效的治疗方法。然而，这些治疗方法对 2 型糖尿病（T2DM）患者的疗效较差。此外，BMI 较高或治疗周期较长的患者体重下降明显大于 BMI 较低或治疗周期较短的患者。在安全性方面，无 T2DM 患者的不良事件发生率高于有 T2DM 患者。所有干预措施均未增加严重不良事件或低血糖事件的发生率（˂54mg/dL）。在头对头比较中，所有干预措施的不良事件停药发生率没有显著差异。此外，种族、BMI 和治疗周期的差异并没有显著增加不良事件的发生率。最后，敏感性和发表偏倚分析表明，基本分析结果是可靠的。
与其他 GLP-1 受体激动剂和多激动剂相比，retatrutide（两种剂量）和 tirzepatide 显示出更好的减肥疗效，降低体重和腰围。无 T2DM、BMI 较高和治疗周期较长的患者体重减轻和腰围减少更明显。双重或三重受体激动剂（GLP-1 加葡萄糖依赖性胰岛素促分泌多肽和/或胰高血糖素受体）在减肥方面比 GLP-1 受体激动剂更有效。
