恩格列净与2型糖尿病患者肾功能快速下降发生率：来自EMPA-REG OUTCOME试验的探索性分析

Empagliflozin and Rapid Kidney Function Decline Incidence in Type 2 Diabetes: An Exploratory Analysis From the EMPA-REG OUTCOME Trial.

作者信息

Hadjadj Samy, Cooper Mark E, Steubl Dominik, Petrini Michaela, Hantel Stefan, Mattheus Michaela, Wanner Christoph, Thomas Merlin C

机构信息

Institut du thorax, INSERM, CNRS, Université Nantes, CHU Nantes, Nantes, France.

Department of Diabetes, Monash University, Melbourne, Australia.

出版信息

Kidney Med. 2023 Dec 18;6(3):100783. doi: 10.1016/j.xkme.2023.100783. eCollection 2024 Mar.

DOI:10.1016/j.xkme.2023.100783

PMID:38419787

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10900108/

Abstract

RATIONALE & OBJECTIVE: Kidney function progressively declines in most patients with type 2 diabetes (T2DM). Many develop progressive chronic kidney disease (CKD), but some experience a more rapid decline, with a greater risk of kidney failure and cardiovascular disease. In EMPA-REG OUTCOME, empagliflozin was associated with slower kidney disease progression. This post hoc analysis evaluated the effect of empagliflozin (pooled doses) on the prevalence of a "rapid decliner" phenotype, defined by an annual estimated glomerular filtration rate (eGFR) decline of >3 mL/min/1.73 m.

STUDY DESIGN

This was an exploratory analysis of EMPA-REG OUTCOME, a large randomized, double-blind, placebo-controlled trial in adults with T2DM, established cardiovascular disease and an eGFR of ≥30 mL/min/1.73 m.

SETTING & PARTICIPANTS: Analysis was undertaken on 6,967 participants (99.2%) in whom serial eGFR data was available.

INTERVENTIONS

Patients were randomized (1:1:1) to empagliflozin 10 mg, 25 mg, or placebo in addition to standard of care.

OUTCOMES

Annual change in eGFR over the maintenance phase of treatment (week 4 to last value on treatment) was calculated using linear regression models. Logistic regression analysis was used to investigate differences in rapid decline between the treatment groups.

RESULTS

Over the study period, a rapid decliner phenotype was observed in 188 (9.5%) participants receiving placebo and 134 (3.4%) receiving empagliflozin. After adjusting for other risk factors, this equated to a two-third reduction in odds (OR, 0.32; 95% CI, 0.25-0.40; < 0.001) among participants receiving empagliflozin versus placebo. A comparable risk reduction was observed using a threshold of eGFR decline of >5 mL/min/1.73 m/y (empagliflozin vs placebo, 43 [1.1%] vs 44 [2.2%] participants; OR, 0.47; 95% CI, 0.31-0.72; < 0.001).

LIMITATIONS

This is a post hoc analysis of a trial undertaken in participants with T2DM and CVD. Generalization of findings to other settings remains to be established.

CONCLUSIONS

Patients receiving empagliflozin were significantly less likely to experience a rapid decline in eGFR over a median of 2.6 years of exposure to the study drug.

FUNDING

The Boehringer Ingelheim and Eli Lilly and Company Diabetes Alliance.

TRIAL REGISTRATION

clinicaltrials.gov ID: NCT01131676.

摘要

原理与目的

大多数2型糖尿病（T2DM）患者的肾功能会逐渐下降。许多患者会发展为进行性慢性肾脏病（CKD），但有些患者肾功能下降更快，肾衰竭和心血管疾病风险更高。在EMPA-REG OUTCOME研究中，恩格列净与减缓肾病进展相关。这项事后分析评估了恩格列净（合并剂量）对“快速下降者”表型患病率的影响，该表型定义为年估计肾小球滤过率（eGFR）下降>3 mL/min/1.73m²。

研究设计

这是对EMPA-REG OUTCOME研究的探索性分析，该研究是一项针对患有T2DM、已确诊心血管疾病且eGFR≥30 mL/min/1.73m²的成年人的大型随机、双盲、安慰剂对照试验。

地点与参与者

对6967名参与者（99.2%）进行了分析，这些参与者有连续的eGFR数据。

干预措施

除标准治疗外，患者被随机（1:1:1）分为接受10mg、25mg恩格列净或安慰剂治疗。

结局指标

使用线性回归模型计算治疗维持阶段（第4周至治疗最后值）eGFR的年变化。采用逻辑回归分析研究治疗组之间快速下降的差异。

结果

在研究期间，接受安慰剂的188名（9.5%）参与者和接受恩格列净的134名（3.4%）参与者出现了快速下降者表型。在调整其他风险因素后，接受恩格列净的参与者与接受安慰剂的参与者相比，这相当于降低了三分之二的几率（OR，0.32；95%CI，0.25 - 0.40；P<0.001）。使用eGFR下降>5 mL/min/1.73m²/年的阈值时，观察到了类似的风险降低（恩格列净组与安慰剂组分别为43名[1.1%]和44名[2.2%]参与者；OR，0.47；95%CI，0.31 - 0.72；P<0.001）。