Chen Jui-Yi, Hsu Tsuen-Wei, Liu Jung-Hua, Pan Heng-Chih, Lai Chun-Fu, Yang Shao-Yu, Wu Vin-Cent
Division of Nephrology, Department of Internal Medicine, Chi Mei Medical Center, Tainan; Department of Health and Nutrition, Chia Nan University of Pharmacy and Science, Tainan.
Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung.
Am J Kidney Dis. 2025 May;85(5):555-569.e1. doi: 10.1053/j.ajkd.2024.11.013. Epub 2025 Jan 23.
RATIONALE & OBJECTIVE: Glucagon-like peptide 1 (GLP-1) receptor agonists improve cardiac and kidney outcomes in patients with diabetes; however, their efficacy in individuals with reduced estimated glomerular filtration rate (eGFR) is uncertain. This study evaluated the effects of GLP-1 receptor agonists on kidney and cardiovascular (CV) outcomes in patients with chronic kidney disease (CKD).
Systematic review and meta-analysis of randomized controlled trials (RCTs) reported through May 25, 2024.
SETTING & STUDY POPULATIONS: Adult participants in RCTs with baseline eGFR<60mL/min/1.73m.
RCTs including adults (≥18 years old) with varying degrees of kidney function, including individuals with CKD characterized by a baseline eGFR of<60mL/min/1.73m, that compared GLP-1 receptor agonists with control treatments with respect to a composite kidney outcome, all-cause mortality, or a composite CV disease outcome. From among 212 screened studies, 12 trials involving that included participants with baseline eGFR<60mL/min/1.73m were included.
Two independent investigators extracted the data.
Pooled odds ratios (ORs) for composite kidney outcome, all-cause mortality, and composite CV outcome were estimated using random-effects models. Evidence certainty was assessed using the GRADE system.
The analyses included 17,996 RCT participants with baseline eGFR<60mL/min/1.73m. GLP-1 receptor agonists were significantly associated with a reduced risk of the composite kidney outcome (OR, 0.85 [95% CI, 0.77-0.94]; P=0.001) with low heterogeneity (I<0.01%). GLP-1 receptor agonists were also associated with a reduced the risk of a>30% eGFR decline (OR, 0.78; P=0.004), a>40% decline (OR, 0.76; P=0.01), and a>50% decline (OR, 0.72; P<0.001). Risk of all-cause mortality was also lower in the GLP-1 receptor agonist group (OR, 0.77 [95% CI, 0.60-0.98], P=0.03), though there was high heterogeneity (I=71.6%). Composite CV outcomes were also lower with the use of a GLP-1 receptor agonist (OR, 0.86 [95% CI, 0.74-0.99], P=0.03; I=40.3%). Sensitivity analyses restricted to human GLP-1 backbone agents showed enhanced benefits.
Inconsistent kidney outcome definitions, focus on diabetic populations in most studies, and potential publication bias.
GLP-1 receptor agonists improved kidney and CV outcomes, and survival in patients with CKD enrolled in an array of clinical trials.
Registered at PROSPERO with identification number CRD42023449059.
PLAIN-LANGUAGE SUMMARY: Glucagon-like peptide 1 (GLP-1) receptor agonists reduce body weight and improve glycemic control. They also have been shown to protect the heart and kidney in people with diabetes. However, the extrapolation of these findings to those with chronic kidney disease (CKD) is uncertain. This study meta-analyzed data from clinical trials focusing on patients with CKD and noted that GLP-1 receptor agonists may slow kidney disease progression and lower the risk of heart disease, stroke, and death. These findings suggest that GLP-1 receptor agonists offer multiple kidney and cardiovascular benefits to people with CKD.
胰高血糖素样肽1（GLP-1）受体激动剂可改善糖尿病患者的心脏和肾脏预后；然而，其在估算肾小球滤过率（eGFR）降低的个体中的疗效尚不确定。本研究评估了GLP-1受体激动剂对慢性肾脏病（CKD）患者肾脏和心血管（CV）预后的影响。
对截至2024年5月25日报告的随机对照试验（RCT）进行系统评价和荟萃分析。
RCT中的成年参与者，基线eGFR<60mL/min/1.73m²。
RCT包括不同程度肾功能的成年人（≥18岁），包括基线eGFR<60mL/min/1.73m²的CKD患者，这些研究比较了GLP-1受体激动剂与对照治疗在复合肾脏结局、全因死亡率或复合心血管疾病结局方面的差异。在212项筛选研究中，纳入了12项涉及基线eGFR<60mL/min/1.73m²参与者的试验。
两名独立研究人员提取数据。
使用随机效应模型估计复合肾脏结局、全因死亡率和复合CV结局的合并比值比（OR）。使用GRADE系统评估证据的确定性。
分析纳入了17996名基线eGFR<60mL/min/1.73m²的RCT参与者。GLP-1受体激动剂与复合肾脏结局风险降低显著相关（OR，0.85[95%CI，0.77 - 0.94]；P = 0.001），异质性低（I²<0.01%）。GLP-1受体激动剂还与eGFR下降>30%的风险降低相关（OR，0.78；P = 0.004），下降>40%（OR，0.76；P = 0.01）和下降>50%（OR，0.72；P<0.001）相关。GLP-1受体激动剂组的全因死亡率风险也较低（OR，0.77[95%CI，0.60 - 0.98]，P = 0.03），尽管异质性高（I² = 71.6%）。使用GLP-1受体激动剂时复合CV结局也较低（OR，0.86[95%CI，0.74 - 0.99]，P = 0.03；I² = 40.3%）。限于人GLP-1主链药物的敏感性分析显示益处增强。
肾脏结局定义不一致，大多数研究关注糖尿病患者群体，以及潜在的发表偏倚。
GLP-1受体激动剂改善了一系列临床试验中CKD患者的肾脏和CV结局以及生存率。
在PROSPERO注册，识别号为CRD42023449059。
胰高血糖素样肽1（GLP-1）受体激动剂可减轻体重并改善血糖控制。它们还被证明对糖尿病患者的心脏和肾脏有保护作用。然而，将这些发现外推至慢性肾脏病（CKD）患者尚不确定。本研究对关注CKD患者的临床试验数据进行了荟萃分析，并指出GLP-1受体激动剂可能减缓肾脏疾病进展并降低心脏病、中风和死亡风险。这些发现表明GLP-1受体激动剂为CKD患者带来多种肾脏和心血管益处。
