Abstract：
OBJECTIVE: The present systematic review aimed to summarize the available evidence from published randomized controlled trials (RCTs) regarding the effect of tirzepatide on albuminuria levels and renal function in patients with type 2 diabetes mellitus.
METHODS: Medline (via PubMed), Cochrane Library and Scopus were searched until 20 October 2023. Double-independent study selection, data extraction and quality assessment were performed. Evidence was pooled with a three-level mixed-effects meta-analysis.
RESULTS: In total, 9533 participants from eight RCTs were analysed. All RCTs had a low risk of bias, according to the Cochrane Collaboration tool (RoB2). Tirzepatide was associated with a significantly greater reduction in urine albumin-to-creatinine ratio compared with controls [mean difference (MD) -26.9%; 95% confidence interval (CI) (-34.76, -19.04); p < .001; level of evidence (LoE) moderate]. This effect remained significant in participants with baseline urine albumin-to-creatinine ratio ≥30 mg/g [MD -41.42%; 95% CI (-54.38, -28.45); p < .001; LoE moderate]. Based on subgroup analysis, the comparative effect of tirzepatide was significant against placebo and the insulin regimen, whereas no difference was observed compared with semaglutide. The beneficial effect of tirzepatide on albuminuria levels remained significant across all investigated doses (5, 10 and 15 mg), showing a dose-response relationship. A neutral effect was observed on the estimated glomerular filtration rate [MD 0.39 ml/min/1.73m2 ; 95% CI (-0.64, 1.42); p = .46; LoE moderate].
CONCLUSIONS: Our findings suggest that tirzepatide probably leads to a significant reduction in albuminuria across all administered doses, while its use is associated with a neutral effect on creatinine clearance as a measure of renal function.
METHODS: Medline (via PubMed), Cochrane Library and Scopus were searched until 20 October 2023. Double-independent study selection, data extraction and quality assessment were performed. Evidence was pooled with a three-level mixed-effects meta-analysis.
RESULTS: In total, 9533 participants from eight RCTs were analysed. All RCTs had a low risk of bias, according to the Cochrane Collaboration tool (RoB2). Tirzepatide was associated with a significantly greater reduction in urine albumin-to-creatinine ratio compared with controls [mean difference (MD) -26.9%; 95% confidence interval (CI) (-34.76, -19.04); p < .001; level of evidence (LoE) moderate]. This effect remained significant in participants with baseline urine albumin-to-creatinine ratio ≥30 mg/g [MD -41.42%; 95% CI (-54.38, -28.45); p < .001; LoE moderate]. Based on subgroup analysis, the comparative effect of tirzepatide was significant against placebo and the insulin regimen, whereas no difference was observed compared with semaglutide. The beneficial effect of tirzepatide on albuminuria levels remained significant across all investigated doses (5, 10 and 15 mg), showing a dose-response relationship. A neutral effect was observed on the estimated glomerular filtration rate [MD 0.39 ml/min/1.73m2 ; 95% CI (-0.64, 1.42); p = .46; LoE moderate].
CONCLUSIONS: Our findings suggest that tirzepatide probably leads to a significant reduction in albuminuria across all administered doses, while its use is associated with a neutral effect on creatinine clearance as a measure of renal function.
摘要：
目的：本系统综述旨在总结已发表的随机对照试验（RCTs）中关于替瑞沙肽对2型糖尿病患者白蛋白尿水平和肾功能影响的现有证据。
方法：Medline（通过PubMed），搜索Cochrane图书馆和Scopus，直到2023年10月20日。双独立研究选择，进行数据提取和质量评估.将证据与三级混合效应荟萃分析进行汇总。
结果：总计，对来自8个随机对照试验的9533名参与者进行了分析。所有RCT的偏倚风险都很低，根据Cochrane协作工具(RoB2)。与对照组相比，Tirzepatide与尿白蛋白/肌酐比值的显著降低相关[平均差(MD)-26.9%;95%置信区间(CI)(-34.76,-19.04);p<.001;证据水平(LoE)中等]。在基线尿白蛋白/肌酐比值≥30mg/g的参与者中，这种影响仍然显着[MD-41.42％;95％CI（-54.38，-28.45）;p<.001;LoE中度]。基于子群分析，与安慰剂和胰岛素方案相比，替利西帕肽的比较效果显着，而与司马鲁肽相比没有观察到差异。在所有研究剂量（5、10和15mg）中，替瑞哌肽对蛋白尿水平的有益作用仍然显着，显示剂量反应关系。对估计的肾小球滤过率观察到中性效应[MD0.39ml/min/1.73m2;95％CI（-0.64，1.42）;p=.46;LoE中等]。
结论：我们的研究结果表明，在所有给药剂量中，替瑞哌肽可能导致蛋白尿的显著减少。而它的使用与肌酐清除率作为肾功能指标的中性作用有关。
方法：Medline（通过PubMed），搜索Cochrane图书馆和Scopus，直到2023年10月20日。双独立研究选择，进行数据提取和质量评估.将证据与三级混合效应荟萃分析进行汇总。
结果：总计，对来自8个随机对照试验的9533名参与者进行了分析。所有RCT的偏倚风险都很低，根据Cochrane协作工具(RoB2)。与对照组相比，Tirzepatide与尿白蛋白/肌酐比值的显著降低相关[平均差(MD)-26.9%;95%置信区间(CI)(-34.76,-19.04);p<.001;证据水平(LoE)中等]。在基线尿白蛋白/肌酐比值≥30mg/g的参与者中，这种影响仍然显着[MD-41.42％;95％CI（-54.38，-28.45）;p<.001;LoE中度]。基于子群分析，与安慰剂和胰岛素方案相比，替利西帕肽的比较效果显着，而与司马鲁肽相比没有观察到差异。在所有研究剂量（5、10和15mg）中，替瑞哌肽对蛋白尿水平的有益作用仍然显着，显示剂量反应关系。对估计的肾小球滤过率观察到中性效应[MD0.39ml/min/1.73m2;95％CI（-0.64，1.42）;p=.46;LoE中等]。
结论：我们的研究结果表明，在所有给药剂量中，替瑞哌肽可能导致蛋白尿的显著减少。而它的使用与肌酐清除率作为肾功能指标的中性作用有关。
