【摘要】 目的 系统评价胰高血糖素样肽-1受体激动剂（GLP-1RA）复合制剂或联合胰岛素在血糖控制不佳的2型糖尿病（T2DM）患者中的有效性和安全性。方法 检索数据库PubMed、Embase、Cochrane Library、CNKI、Sinomed、VIP、万方，检索范围为建库至2024年10月20日，根据入排严格筛选胰岛素或GLP-1RA治疗血糖控制不佳T2DM患者接受GLP-1RA复合制剂或联合胰岛素治疗的随机对照试验，提取数据，进行网状Meta分析。结果 纳入随机对照试验40项，共计18 215例T2DM患者，与GLP-1RA比较，替尔泊肽、司美格鲁肽联合胰岛素降低糖化血红蛋白效果好[加权均数差（WMD）:-1.38,95%CI:-2.03～-0.73;WMD:-1.30,95%CI:-2.02～-0.58]，降低空腹血糖效果好（WMD:-3.30,95%CI:-4.17～-2.43;WMD:-2.93, 95%CI:-3.90～-1.96），降低餐后2 h血糖无显著差异（WMD 95%CI包含0）；替尔泊肽减重优异（WMD:-6.23,95%CI:-9.45～-3.01）；在总不良事件风险、严重低血糖风险、胰腺炎风险、主要不良心血管事件风险方面均无显著差异（OR值及95%CI包含1）；司美格鲁肽联合胰岛素因不良事件停药风险较高（OR=6.76,95%CI:1.50～30.49）。结论 在血糖控制不佳的T2DM患者中，替尔泊肽降糖、管理体质量效果最佳且安全性高；司美格鲁肽联合胰岛素降糖优异、安全性较高，然而因不良事件停药风险较高；GLP-1RA联合胰岛素虽增强降糖效果，但需权衡治疗复杂性，本研究可为临床治疗策略提供循证依据。更多还原

【Abstract】 Objective To systematically evaluate the efficacy and safety of GLP-1 receptor agonist(GLP-1 RA) fixed-dose combination or combination with insulin in patients with poorly controlled type 2 diabetes mellitus(T2 DM). Methods Databases including PubMed, Embase, Cochrane Library, CNKI, Sinomed, VIP, and Wanfang were searched from inception to October 20, 2024. Randomized controlled trials(RCT) involving T2 DM patients with poor glycemic control treated with GLP-1 RA fixed-dose combinations or GLP-1 RA combined with insulin were strictly screened according to inclusion and exclusion criteria. Data were extracted and a network meta-analysis was conducted. Results A total of 40 RCTs involving 18 215 T2 DM patients were included. Compared with GLP-1 RA, Tirzepatide and Semaglutide combined with insulin showed superior effects in reducing HbA1c(WMD:-1.38, 95%CI:-2.03--0.73; WMD:-1.30, 95%CI:-2.02--0.58) and fasting plasma glucose(WMD:-3.30, 95%CI:-4.17--2.43; WMD:-2.93, 95%CI:-3.90--1.96). There was no significant difference in reducing 2-hour postprandial blood glucose(the 95%CI of WMD included 0). Tirzepatide demonstrated excellent weight loss effect(WMD:-6.23, 95%CI:-9.45--3.01). No significant differences were observed in the risks of total adverse events, severe hypoglycemia, pancreatitis, or major adverse cardiovascular events(the 95%CI of OR included 1). Semaglutide combined with insulin had a higher risk of discontinuation due to adverse events(OR=6.76, 95%CI: 1.50–30.49). Conclusion In patients with poorly controlled T2 DM, Tirzepatide provides the best glycemic control and weight management effects with high safety; Semaglutide combined with insulin offers excellent glycemic control and high safety, but carries a higher risk of discontinuation due to adverse events. Although GLP-1 RA combined with insulin enhances glycemic control, the complexity of treatment requires careful consideration. This study provides evidence-based insights for clinical treatment strategies.更多还原