Key Specialty of Clinical Pharmacy, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China.
Front Endocrinol (Lausanne). 2023 Aug 28;14:1244432. doi: 10.3389/fendo.2023.1244432. eCollection 2023.
This study aimed to perform a network meta-analysis to objectively evaluate the efficacy and safety of 10 Glucagon-like peptide-1 receptor agonists (GLP-1RAs) in combination with metformin that is approved for use worldwide in patients with type 2 diabetes and to provide evidence-based support and reference for the selection of clinical treatment.
Three databases (PubMed, Embase, and Cochrane Library) were searched from their respective inception until September 30, 2022. Only randomized controlled trials comparing the efficacy and safety of GLP-1RAs for treating type 2 diabetes (T2D) were included. The 10 GLP-1RAs are exenatide (including exenatide twice daily and once weekly), liraglutide, lixisenatide, dulaglutide, PEX168, semaglutide (subcutaneous and oral semaglutide), tirzepatide and albiglutide.
34 RCTs with 10 GLP-1RAs and 12993 patients were included in the Network Meta-Analysis (NMA). According to the NMA, tirzepatide 15 mg, semaglutide 1.0 mg, PEX168-200μg, oral semaglutide 14 and dulaglutide 1.5 mg reduced HbA1c by -2.23%, -1.57%, -1.12%, -1.10%, -1.09% and body weight by -11.33 kg, -5.99 kg, +0.40 kg, -3.95 kg, -1.87 kg, respectively. There was no significant difference in the rate of adverse events for tirzepatide 15 mg, oral-semaglutide 14 mg, and semaglutide 1.0 mg. PEX168-200μg, tirzepatide 15mg, and oral semaglutide 14mg had Surface Under the Cumulative Ranking (SUCRA) values greater than placebo, and only tirzepatide 15mg and oral semaglutide 14mg were significantly different from placebo in the rate of serious adverse events. All GLP-1RA did not lead to increased incidence of hypoglycemia. Albiglutide 30mg and semaglutide 1.0mg significantly differed from placebo in Adverse Event (AE) withdrawal. Finally, the sensitivity analysis and publication bias analysis results indicate that the study results are reliable.
This study's results showed that GLP-1RAs were effective in lowering HbA1c and reducing body weight without increased incidence of hypoglycemic reactions. In addition, this study may provide reference and evidence-based medical evidence for clinicians to select GLP-1RAs in patients with T2D and high body mass index (BMI). Based on the NMA results, tirzepatide 15mg and semaglutide 1.0mg may be preferred.
本研究旨在通过网络荟萃分析客观评估 10 种已在全球获批用于治疗 2 型糖尿病的 GLP-1 受体激动剂（GLP-1RAs）与二甲双胍联合使用的疗效和安全性，并为临床治疗选择提供循证支持和参考。
从各自的成立日期到 2022 年 9 月 30 日，检索了 3 个数据库（PubMed、Embase 和 Cochrane Library）。仅纳入比较 GLP-1RAs 治疗 2 型糖尿病（T2D）疗效和安全性的随机对照试验。纳入的 10 种 GLP-1RAs 为艾塞那肽（包括艾塞那肽每日两次和每周一次）、利拉鲁肽、利西那肽、度拉糖肽、PEX168、司美格鲁肽（皮下和口服司美格鲁肽）、替西帕肽和阿必鲁肽。
纳入的网络荟萃分析（NMA）共包括 34 项 RCT 和 12993 例患者。根据 NMA，替西帕肽 15mg、司美格鲁肽 1.0mg、PEX168-200μg、口服司美格鲁肽 14mg 和度拉糖肽 1.5mg 可分别使 HbA1c 降低 2.23%、1.57%、1.12%、1.10%和 1.09%，体重减轻 11.33kg、5.99kg、+0.40kg、-3.95kg 和-1.87kg。替西帕肽 15mg、口服司美格鲁肽 14mg 和司美格鲁肽 1.0mg 的不良事件发生率无显著差异。PEX168-200μg、替西帕肽 15mg 和口服司美格鲁肽 14mg 的表面累积排序概率（SUCRA）值大于安慰剂，且仅替西帕肽 15mg 和口服司美格鲁肽 14mg 的严重不良事件发生率与安慰剂相比有显著差异。所有 GLP-1RA 均未导致低血糖发生率增加。阿必鲁肽 30mg 和司美格鲁肽 1.0mg 与安慰剂在不良事件（AE）退出率方面有显著差异。最后，敏感性分析和发表偏倚分析结果表明，研究结果可靠。
本研究结果表明，GLP-1RAs 可有效降低 HbA1c 和体重，且不会增加低血糖反应的发生。此外，本研究可能为临床医生在治疗 T2D 合并高体重指数（BMI）患者时选择 GLP-1RAs 提供参考和循证医学证据。根据 NMA 结果，替西帕肽 15mg 和司美格鲁肽 1.0mg 可能是更好的选择。
