Zou Xinyu, Shi Qingyang, Olav Vandvik Per, Mao Yunhe, Agarwal Arnav, Ponte Belen, Zeng Xiaoxi, Guyatt Gordon, Yang Qinbo, Luo Xianghang, Xu Chang, Fu Ping, Tian Haoming, Agoritsas Thomas, Li Sheyu
Department of Endocrinology and Metabolism, MAGIC China Centre, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
Faculty of Science and Engineering, University of Groningen, Groningen, the Netherlands.
BMJ Med. 2024 Oct 1;3(1):e001009. doi: 10.1136/bmjmed-2024-001009. eCollection 2024.
To examine cardiovascular and kidney benefits and harms of sodium-glucose co-transporter-2 (SGLT-2) inhibitors stratified by risk in adults with chronic kidney disease regardless of diabetes status.
Systematic review and meta-analysis.
Ovid Medline, Embase, and Cochrane Central from database inception to 15 June 2024.
Randomised controlled trials that compared SGLT-2 inhibitors with placebo or standard care with no SGLT-2 inhibitors in adults with chronic kidney disease with a follow-up duration of ≥12 weeks were eligible. Secondary analyses based on subpopulations from randomised controlled trials and publications not in English language were excluded.
Random effects meta-analyses were conducted, with effect estimates presented as risk ratios with 95% confidence intervals (CIs). Absolute treatment effects were estimated over a five year duration for individuals with varied risks of cardiovascular and kidney complications based on the Kidney Disease Improving Global Outcomes (KDIGO) risk stratification system. Certainty of evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach.
Evidence from 13 randomised controlled trials (29 614 patients) informed treatment effect estimates. In relative terms, SGLT-2 inhibitors reduced all cause death (risk ratio 0.85 (95% CI 0.74 to 0.98)), cardiovascular death (0.84 (0.74 to 0.96)), kidney failure (0.68 (0.60 to 0.77)), non-fatal stroke (0.73 (0.57 to 0.94)), non-fatal myocardial infarction (0.75 (0.60 to 0.93)), and admission to hospital for heart failure (0.68 (0.60 to 0.78)). No credible subgroup effects were found from diabetes status, heart failure status, estimated glomerular filtration rate, urinary albumin-to-creatinine ratio, and follow-up duration. Absolute effect estimates across these outcomes over a five year period varied across risk groups based on baseline risks of cardiovascular and kidney events. Effects of SGLT-2 inhibitors in the group at low risk included seven fewer all- cause deaths, four fewer admissions to hospital for heart failure per 1000 individuals, and no effects on kidney failure. Effects in the higher risk group included 48 fewer all cause deaths, 58 fewer kidney failures, and 25 fewer admissions to hospital for heart failure per 1000 individuals. Although SGLT-2 inhibitor use was associated with a relative increase in the risk of harms, including genital infection (2.66 (95% CI 2.07 to 3.42)), ketoacidosis (2.27 (1.30 to 3.95)), and symptomatic hypovolaemia (1.29 (1.15 to 1.44)), absolute differences for all harm outcomes were small.
Among people who have chronic kidney disease either with type 2 diabetes or not, SGLT-2 inhibitors improved cardiovascular and kidney outcomes with varying degrees of absolute benefit depending on an individual's baseline risks of cardiovascular and kidney-related sequelae. Absolute benefits and harms stratified by risk and associated with SGLT-2 inhibitors should inform individual decision making at the patient level.
PROSPERO CRD42022325483.
探讨钠-葡萄糖协同转运蛋白2（SGLT-2）抑制剂对慢性肾脏病成人患者心血管和肾脏的益处与危害，并根据风险进行分层，无论其糖尿病状态如何。
系统评价和荟萃分析。
从数据库建立至2024年6月15日的Ovid Medline、Embase和Cochrane Central。
比较SGLT-2抑制剂与安慰剂或无SGLT-2抑制剂的标准治疗的随机对照试验，受试者为慢性肾脏病成人患者，随访时间≥12周。排除基于随机对照试验亚组人群的二次分析以及非英文出版物。
进行随机效应荟萃分析，效应估计值以风险比及95%置信区间（CI）表示。根据改善全球肾脏病预后组织（KDIGO）风险分层系统，对心血管和肾脏并发症风险各异的个体，估计其5年期间的绝对治疗效果。采用GRADE（推荐分级、评估、制定与评价）方法评估证据的确定性。
13项随机对照试验（29614例患者）的证据为治疗效果估计提供了依据。相对而言，SGLT-2抑制剂降低了全因死亡（风险比0.85（95%CI 0.74至0.98））、心血管死亡（0.84（0.74至0.96））、肾衰竭（0.68（0.60至0.77））、非致死性卒中（0.
