GLP-1RA联合SGLT2抑制剂治疗糖尿病肾病的Meta分析

GLP-1RA Combined with SGLT2 Inhibitors for the Treatment of Diabetic Kidney Disease: A Meta Analysis

摘要: 目的：运用Meta分析的方法评估GLP-1RA联合SGLT-2i抑制剂治疗糖尿病肾病的有效性和安全性。方法：检索CNKI、万方数据库、VIP、SinoMed、PubMed、Embase、Cochrane Library、Ovid、Web of Science中关于GLP-1RA联合SGLT-2i治疗糖尿病肾病的实验性研究，检索时间从各数据库建库至2023年6月25日。主要结局指标包括糖化血红蛋白(HbA1c)、血清肌酐(Scr)、尿素氮(BUN)、尿微量白蛋白肌酐比值(UACR)、估计肾小球滤过率(eGFR)、低血糖发生率。采用RevMan5.4和Stata16.0进行Meta分析。结果：本研究共纳入10篇文献，分析结果显示在有效性方面GLP-1RA联合SGLT-2i与单用GLP-1RA或SGLT-2i相比在降低HbA1c [WMD = −0.506, 95% CI (−0.786, −0.227), P = 0.000]、Scr [WMD = −8.21, 95% CI (−12.55, −3.87), P = 0.000]、BUN [WMD = −1.224, 95% CI (−1.674, −0.774), P = 0.000]、UACR [WMD = −20.94, 95% CI (−32.89, −8.99), P = 0.000]方面具有优势，但在降低eGFR方面联合治疗并不优于单药治疗[WMD = −3.310, 95% CI (−13.073, 6.454), P = 0.506]。亚组分析结果显示当疗程大于3个月时，GLP-1RA联合SGLT-2i降低HbA1C、Scr、BUN的效果与单药相比无明显差异(P_HbA1c = 0.770, P_Scr = 0.735, P_BUN = 0.855)。在安全性方面，GLP-1RA联合SGLT-2i不会增加低血糖的发生风险[OR = 1.818, 95% CI (0.799, 4.139), P = 0.154]。结论：GLP-1RA联合SGLT-2i与单用GLP-1RA或SGLT-2i比较，能有效降低HbA1c、Scr、BUN、UACR水平，且不会增加低血糖发生风险，具有良好的有效性和安全性。

Abstract: Objective: To use Meta analysis method to evaluate the effectiveness and safety of GLP-1RA com-bined with SGLT-2i inhibitors in the treatment of diabetic nephropathy. Methods: Search CNKI, Wanfang Database, VIP, SinoMed, PubMed, Embase, Cochrane Library, Ovid, and Web of Science for experimental studies on GLP-1RA combined with SGLT-2i in the treatment of diabetic nephropathy. The search time was from the establishment of each database to June 25, 2023. The main outcome indicators included glycosylated hemoglobin (HbA1c), serum creatinine (Scr), urea nitrogen (BUN), urinary microalbumin to creatinine ratio (UACR), estiMetad glomerular filtration rate (eGFR), and the incidence of hypoglycemia. RevMan5.4 and Stata16.0 were used for Meta analysis. Results: A total of 10 documents were included in this study, and the analysis results showed that in terms of effectiveness, GLP-1RA combined with SGLT-2i was more effective in reducing HbA1c than GLP-1RA or SGLT-2i alone [WMD = −0.506, 95% CI (−0.786, −0.227), P = 0.000], Scr [WMD = −8.21, 95% CI (−12.55, −3.87), P = 0.000], BUN [WMD = −1.224, 95% CI (−1.674, −0.774), P = 0.000], UACR [WMD = −20.94, 95% CI (−32.89, −8.99), P = 0.000] has advantages, but combination therapy is not better than monotherapy in reducing eGFR [WMD = −3.310, 95% CI (−13.073, 6.454), P = 0.506]. Sub-group analysis results showed that when the treatment course was more than 3 months, the effect of GLP-1RA combined with SGLT-2i in reducing HbA1C, Scr, and BUN was not significantly different from that of single drug (P_HbA1c = 0.770, P_Scr = 0.735, P_BUN = 0.855). In terms of safety, GLP-1RA com-bined with SGLT-2i will not increase the risk of hypoglycemia [OR = 1.818, 95% CI (0.799, 4.139), P = 0.154]. Conclusion: GLP-1RA combined with SGLT-2i can effectively reduce HbA1c, Scr, BUN, and UACR levels compared with GLP-1RA or SGLT-2i alone, without increasing the risk of hypoglycemia, and have good effectiveness and safety.