本文由小咖机器人翻译整理

期刊来源：N Engl J Med

原文链接：https://doi.org/10.1056/NEJMoa2403347

摘要内容如下：

背景

2型糖尿病和慢性肾病患者是肾衰竭、心血管事件和死亡的高危人群。用semaglutide治疗是否会减轻这些风险尚不清楚。

方法

我们将2型糖尿病合并慢性肾脏疾病（定义为估计的肾小球滤过率[EGFR]为每分钟50-75 mL/1.73 m2体表面积，尿白蛋白-肌酐比值[白蛋白以毫克计，肌酐以克计]>300且<5000；或EGFR为每分钟25-<50 mL/1.73 m2，尿白蛋白-肌酐比值>100且<5000）患者随机分配至接受每周1.0 mg剂量的皮下注射semaglutide或安慰剂。主要转归是主要肾脏疾病事件，即肾衰竭发作（透析、移植或EGFR<15 mL/min/1.73 m2）、EGFR较基线至少降低50%或肾脏相关或心血管原因导致的死亡的复合事件。对预先指定的验证性次要结果进行分层测试。

结果

在接受随机分组的3533名参与者（Semaglutide组1767名，安慰剂组1766名）中，中位随访时间为3.4年，在预先指定的中期分析中建议早期停止试验。与安慰剂组相比，semaglutide组的主要结局事件风险降低了24%（331对410首次事件；风险比为0.76；95%置信区间[CI]，0.66至0.88；P=0.0003）。主要转归的肾脏特异性复合成分的结果相似（风险比为0.79；95%CI，0.66至0.94）和心血管原因死亡（风险比，0.71；95%置信区间，0.56至0.89）。所有验证性次要转归的结果均有利于semaglutide：semaglutide组的平均年EGFR斜率不太陡（表明下降较慢），为1.16 mL/min/1.73 m2（p<0.001），主要心血管事件的风险降低18%（风险比为0.82；95%可信区间为0.68~0.98；P=0.029），任何原因导致的死亡风险降低20%（风险比为0.80；95%可信区间为0.67~0.95，P=0.01）。与安慰剂组相比，Semaglutide组参与者报告严重不良事件的比例较低（49.6%对53.8%）。

结论

在2型糖尿病和慢性肾病患者中，Semaglutide降低了临床上重要的肾脏结局和心血管原因死亡的风险。（由Novo Nordisk资助；Flow ClinicalTrials.gov编号，NCT03819153。）

英文原文如下：

Abstracts

BACKGROUND  Patients with type 2 diabetes and chronic kidney disease are at high risk for kidney failure, cardiovascular events, and death. Whether treatment with semaglutide would mitigate these risks is unknown.

METHODS  We randomly assigned patients with type 2 diabetes and chronic kidney disease (defined by an estimated glomerular filtration rate [eGFR] of 50 to 75 ml per minute per 1.73 m2 of body-surface area and a urinary albumin-to-creatinine ratio [with albumin measured in milligrams and creatinine measured in grams] of >300 and <5000 or an eGFR of 25 to <50 ml per minute per 1.73 m2 and a urinary albumin-to-creatinine ratio of >100 and <5000) to receive subcutaneous semaglutide at a dose of 1.0 mg weekly or placebo. The primary outcome was major kidney disease events, a composite of the onset of kidney failure (dialysis, transplantation, or an eGFR of <15 ml per minute per 1.73 m2), at least a 50% reduction in the eGFR from baseline, or death from kidney-related or cardiovascular causes. Prespecified confirmatory secondary outcomes were tested hierarchically.

RESULTS  Among the 3533 participants who underwent randomization (1767 in the semaglutide group and 1766 in the placebo group), median follow-up was 3.4 years, after early trial cessation was recommended at a prespecified interim analysis. The risk of a primary-outcome event was 24% lower in the semaglutide group than in the placebo group (331 vs. 410 first events; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.88; P = 0.0003). Results were similar for a composite of the kidney-specific components of the primary outcome (hazard ratio, 0.79; 95% CI, 0.66 to 0.94) and for death from cardiovascular causes (hazard ratio, 0.71; 95% CI, 0.56 to 0.89). The results for all confirmatory secondary outcomes favored semaglutide: the mean annual eGFR slope was less steep (indicating a slower decrease) by 1.16 ml per minute per 1.73 m2 in the semaglutide group (P<0.001), the risk of major cardiovascular events 18% lower (hazard ratio, 0.82; 95% CI, 0.68 to 0.98; P = 0.029), and the risk of death from any cause 20% lower (hazard ratio, 0.80; 95% CI, 0.67 to 0.95, P = 0.01). Serious adverse events were reported in a lower percentage of participants in the semaglutide group than in the placebo group (49.6% vs. 53.8%).

CONCLUSIONS  Semaglutide reduced the risk of clinically important kidney outcomes and death from cardiovascular causes in patients with type 2 diabetes and chronic kidney disease. (Funded by Novo Nordisk; FLOW ClinicalTrials.gov number, NCT03819153.).

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