Diabetic kidney disease is one of the microvascular complications of diabetes mellitus, which significantly impacts the quality of life of patients. Owing to abnormal renal function, the application of traditional hypoglycemic medications is severely restricted. At present, glucagon-like peptide-1 (GLP-1) receptor agonists not only play a role in lowering blood glucose but also exhibit multiple beneficial effects, including renal protection. Nevertheless, considering the numerous types of GLP-1 receptor agonists available, there is a dearth of relevant clinical evidence-based medical data to assess the relative advantages and disadvantages of the therapeutic effects of different GLP-1 receptor agonists.

To systematically assess the therapeutic effects of various GLP-1 receptor agonists on renal function, proteinuria, and glycemic control in patients with diabetic kidney disease.

A comprehensive literature search was conducted across multiple electronic databases, including PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang Data Knowledge Service Platform, VIP Database, and Sinomed. The search strategy combined both subject headings and free-text terms, with retrieval limited to the period from database inception up to March 16, 2025. Randomized controlled trials evaluating the use of various GLP-1 receptor agonists in the treatment of diabetic kidney disease were included. In the experimental groups, patients received GLP-1 receptor agonist therapy, whereas control groups were administered either another GLP-1 receptor agonist or standard conventional treatment. Network meta-analysis and graphical visualization were performed using Stata 16.0 software. The relative efficacy rankings of different GLP-1 receptor agonists across outcome measures were assessed using the surface under the cumulative ranking curve (SUCRA) analysis.

A total of 27 studies involving 7 019 patients were included, encompassing seven GLP-1 receptor agonists: exenatide, dulaglutide, semaglutide, liraglutide, polyethylene glycol lovenatide, benaglutide, and albiglutide. The results of the network meta-analysis indicated that, the estimated glomerular filtration rate (eGFR) levels of patients treated with exenatide (WMD=10.21, 95%CI=3.09-17.34), polyethylene glycol lovenatide (WMD=9.76, 95%CI=1.07-18.46), and liraglutide (WMD=7.13, 95%CI=2.79-11.47) were significantly higher than those of conventional standard therapy (P<0.05). The serum creatinine (Scr) levels of patients treated with semaglutide (WMD=-24.03, 95%CI=-47.72 to -0.33), exenatide (WMD=-17.55, 95%CI=-32.68 to -2.42), and liraglutide (WMD=-10.92, 95%CI=-19.05 to -2.80) were significantly lower than those of conventional standard therapy (P<0.05). Exenatide was also associated with a lower UACR level compared to traditional standard treatment (WMD=-192.45, 95%CI=-353.07 to -31.83; P<0.05). Regarding UAER reduction, dulaglutide (WMD=-228.51, 95%CI=-282.19 to -174.83), exenatide (WMD=-159.67, 95%CI=-295.06 to -24.28), liraglutide (WMD=-34.24, 95%CI=-47.58 to -20.90), and benaglutide (WMD=-16.68, 95%CI=-32.05 to -1.30) showed significantly greater reductions than the control (P<0.05). Furthermore, dulaglutide exhibited a significantly lower UAER level than liraglutide (WMD=-194.27, 95%CI=-249.58 to -138.96; P<0.05), and both dulaglutide (WMD=-211.83, 95%CI=-267.67 to -156.00) and exenatide (WMD=-142.99, 95%CI=-279.26 to -6.73) outperformed benaglutide (P<0.05). Duraglutide (WMD=-2.44, 95%CI=-4.05 to -0.83), semaglutide (WMD=-2.00, 95%CI=-3.80 to -0.20), and liraglutide (WMD=-0.93, 95%CI=-1.64 to -0.22) were associated with significantly lower FPG levels compared to conventional standard therapy (P<0.05). Additionally, dulaglutide demonstrated a lower FPG level than albiglutide(WMD=-2.34, 95%CI=-4.58 to -0.10; P<0.05). Compared with conventional standard therapy, polyethylene glycol lovenatide (WMD=-1.22, 95%CI=-2.09 to -0.35), semaglutide (WMD=-0.81, 95%CI=-1.41 to -0.21), and liraglutide (WMD=-0.60, 95%CI=-0.87 to -0.34) showed significantly better glycemic control (P<0.05). According to SUCRA rankings, exenatide ranked highest in delaying the decline of eGFR and reducing UACR. Semaglutide ranked first in reducing Scr, dulaglutide in reducing UAER and FPG, and pegylated lovenatide in HbA_1c reduction.

A network meta-analysis was conducted to compare the efficacy of seven GLP-1 receptor agonists, and it was found that dulaglutide may be the best choice in reducing urinary albumin excretion rate and controlling fasting blood glucose. There was no significant difference in the improvement of renal function among different GLP-1 receptor agonists. In the future, more high-quality randomized controlled trials with larger sample sizes and more comprehensive types of drugs are needed to verify the results.

糖尿病肾脏病是糖尿病微血管并发症之一，严重影响患者的生命质量，由于肾功能异常，传统的降糖药物使用非常受限。目前胰高血糖素样肽1（GLP-1）受体激动剂在降糖的同时也表现出肾脏保护等多重收益，但鉴于GLP-1受体激动剂种类繁多，缺乏相关临床循证医学证据，难以评估不同种类GLP-1受体激动剂治疗效果的优劣。

系统评价不同GLP-1受体激动剂对糖尿病肾脏病患者肾功能、蛋白尿、血糖控制的治疗效果。

计算机检索PubMed、Embase、Cochrane Library、Web of Science、中国知网、万方数据知识服务平台、维普网、中国生物医学文献服务系统相关文献，检索方案为主题词与自由词相结合，检索时限为从建库至2025-03-16。纳入使用不同GLP-1受体激动剂治疗糖尿病肾脏病患者的随机对照试验，试验组接受GLP-1受体激动剂治疗，对照组接受另1种GLP-1受体激动剂或者传统标准治疗。由2名研究人员提取资料并进行文献质量评价，使用Stata 16.0软件进行网状Meta分析和图形绘制，利用累积排序曲线下面积（SUCRA）图估计不同GLP-1受体激动剂各项结局指标疗效的排名。

共纳入27项研究，7 019例患者，涉及7种GLP-1受体激动剂，分别为：艾塞那肽、度拉糖肽、司美格鲁肽、利拉鲁肽、聚乙二醇洛塞那肽、贝那鲁肽、阿必鲁肽。网状Meta分析结果显示：艾塞那肽（WMD=10.21，95%CI=3.09~17.34）、聚乙二醇洛塞那肽（WMD=9.76，95%CI=1.07~18.46）、利拉鲁肽（WMD=7.13，95%CI=2.79~11.47）治疗的患者估算肾小球滤过率（eGFR）水平高于传统标准治疗（P<0.05）。司美格鲁肽（WMD=-24.03，95%CI=-47.72~-0.33）、艾塞那肽（WMD=-17.55，95%CI=-32.68~-2.42）、利拉鲁肽（WMD=-10.92，95%CI=-19.05~-2.80）治疗的患者血肌酐（Scr）水平低于传统标准治疗（P<0.05）。艾塞那肽（WMD=-192.45，95%CI=-353.07~-31.83）治疗的患者尿白蛋白/肌酐比值（UACR）水平低于传统标准治疗（P<0.05）。度拉糖肽（WMD=-228.51，95%CI=-282.19~-174.83）、艾塞那肽（WMD=-159.67，95%CI=-295.06~-24.28）、利拉鲁肽（WMD=-34.24，95%CI=-47.58~-20.90）、贝那鲁肽（WMD=-16.68，95%CI=-32.05~-1.30）治疗的患者尿白蛋白排泄率（UAER）低于传统标准治疗（P<0.05）。度拉糖肽（WMD=-194.27，95%CI=-249.58~-138.96）治疗的患者UAER水平低于利拉鲁肽（P<0.05）。度拉糖肽（WMD=-211.83，95%CI=-267.67~-156.00）、艾塞那肽（WMD=-142.99，95%CI=-279.26~-6.73）治疗的患者UAER水平低于贝那鲁肽（P<0.05）。度拉糖肽（WMD=-2.44，95%CI=-4.05~-0.83）、司美格鲁肽（WMD=-2.00，95%CI=-3.80~-0.20）、利拉鲁肽（WMD=-0.93，95%CI=-1.64~-0.22）治疗的患者空腹血糖（FPG）低于传统标准治疗（P<0.05）。度拉糖肽（WMD=-2.34，95%CI=-4.58~-0.10）治疗的患者FPG低于阿必鲁肽（P<0.05）。聚乙二醇洛塞那肽（WMD=-1.22，95%CI=-2.09~-0.35）、司美格鲁肽（WMD=-0.81，95%CI=-1.41~-0.21）、利拉鲁肽（WMD=-0.60，95%CI=-0.87~-0.34）治疗的患者糖化血红蛋白（HbA_1c）低于传统标准治疗（P<0.05）。通过SUCRA排序，在延缓eGFR下降、降低UACR方面，艾塞那肽排第1位；在降低Scr方面，司美格鲁肽排第1位；在降低UAER、FPG方面，度拉糖肽排第1位；在减低HbA_1c方面，聚乙二醇洛塞那肽排第1位。

通过网状Meta分析对7种GLP-1受体激动剂的疗效进行对比，发现在降低UAER、控制FPG方面，度拉糖肽可能是最优选择。在改善肾功能方面，不同GLP-1受体激动剂无明显差异。未来仍需要开展样本量更大、药物种类更全面的高质量随机对照试验加以验证。