Kidney and Survival Benefits of Semaglutide in Diabetes With Chronic Kidney Disease: FLOW Trial Cardiovascular Subgroup Analyses.

The study sought to assess semaglutide effects on kidney and survival outcomes by baseline cardiovascular status in the FLOW trial.

该研究旨在通过基线心血管状态评估semaglutide对肾脏和生存结果的影响，研究在FLOW试验中进行。

Methods

Participants with type 2 diabetes and CKD were randomized to once-weekly subcutaneous semaglutide 1.0 mg vs placebo.

参与者为2型糖尿病和慢性肾脏病患者，随机分为每周一次皮下注射1.0毫克司美格鲁肽与安慰剂组。

Baseline subgroups included atherosclerotic cardiovascular disease (ASCVD), heart failure, and high total cardiovascular disease risk without established cardiovascular disease (10-year PREVENT [Predicting Risk of cardiovascular disease EVENTs] score ≥20%).

基线亚组包括动脉粥样硬化性心血管疾病（ASCVD）、心力衰竭以及未确立心血管疾病的高心血管疾病风险（10年预防心血管事件风险评分≥20%）。

The primary outcome was ≥50% estimated glomerular filtration rate (eGFR) decline, eGFR <15 mL/min/1.73 m2, dialysis, transplantation, and kidney or cardiovascular death.

主要结果是估算肾小球滤过率（eGFR）下降≥50%，eGFR <15 mL/min/1.73 m2，透析，移植，以及肾脏或心血管死亡。

All-cause death was a confirmatory secondary outcome.

全因死亡是确认性的次要结果。

Results

At baseline, 1,198 (33.9%) of 3,533, 678 (19.2%) of 3,532, and 1,329 (66.5%) of 2,000 participants had ASCVD, heart failure, or high total cardiovascular disease risk in those without established cardiovascular disease, respectively.

基线时，3,533名参与者中有1,198名（33.9%）患有动脉粥样硬化性心血管疾病（ASCVD），3,532名中有678名（19.2%）患有心力衰竭，而在2,000名无已确立心血管疾病的参与者中，有1,329名（66.5%）具有高心血管疾病风险。

Semaglutide reduced the primary outcome risk in subgroups with (119 of 593 vs 146 of 605) or without (212 of 1,174 vs 264 of 1,161) ASCVD (HR: 0.80; 95% CI: 0.63-1.02; and HR: 0.74; 95% CI: 0.62-0.89, respectively; P for interaction = 0.62), with (67 of 342 vs 88 of 336) or without (264 of 1,424 vs 322 of 1,430) heart failure (HR: 0.67; 95% CI: 0.49-0.93; and HR: 0.79; 95% CI: 0.67-0.93, respectively; P for interaction = 0.40), and with (134 of 675 vs 168 of 654) or without (44 of 331 vs 58 of 340) high total cardiovascular disease risk (HR: 0.73; 95% CI: 0.58-0.91; and HR: 0.73; 95% CI: 0.49-1.08, respectively; P for interaction = 0.99).

Semaglutide在有ASCVD（119/593对比146/605）或无ASCVD（212/1,174对比264/1,161）的亚组中降低了主要结果风险（HR: 0.80; 95% CI: 0.63-1.02; 和 HR: 0.74; 95% CI: 0.62-0.89，分别；交互作用P值=0.62），有心力衰竭（67/342对比88/336）或无心力衰竭（264/1,424对比322/1,430）的亚组中（HR: 0.67; 95% CI: 0.49-0.93; 和 HR: 0.79; 95% CI: 0.67-0.93，分别；交互作用P值=0.40），以及有高心血管疾病风险（134/675对比168/654）或无高心血管疾病风险（44/331对比58/340）的亚组中（HR: 0.73; 95% CI: 0.58-0.91; 和 HR: 0.73; 95% CI: 0.49-1.08，分别；交互作用P值=0.99）。

Numbers needed to treat to prevent 1 primary kidney outcome at 3 years were 22, 13, and 17 in the ASCVD, heart failure, and PREVENT score ≥20% subgroups, respectively.

在动脉粥样硬化性心血管疾病（ASCVD）、心力衰竭和PREVENT评分≥20%的亚组中，3年内预防1例主要肾脏结局所需的治疗人数分别为22、13和17。

Semaglutide also reduced risks of all-cause death with (99 of 593 vs 121 of 605) or without (128 of 1,174 vs 158 of 1,161) ASCVD (HR: 0.82; 95% CI: 0.63-1.07; and HR: 0.78; 95% CI: 0.62-0.99, respectively; P for interaction = 0.79), with (64 of 342 vs 79 of 336) or without (163 of 1,424 vs 200 of 1,430) heart failure (HR: 0.75; 95% CI: 0.54-1.05; and HR: 0.81; 95% CI: 0.66-0.99, respectively; P for interaction = 0.74), and with (73 of 675 vs 98 of 654) or without (23 of 331 vs 28 of 340) high total cardiovascular disease risk (HR: 0.71; 95% CI: 0.52-0.95; and HR: 0.82; 95% CI: 0.47-1.43, respectively; P for interaction = 0.63).

Semaglutide还降低了全因死亡风险，无论是否伴有动脉粥样硬化性心血管疾病（ASCVD）（593人中有99人vs 605人中有121人）或不伴有ASCVD（1,174人中有128人vs 1,161人中有158人）（HR: 0.82; 95% CI: 0.63-1.07; 和 HR: 0.78; 95% CI: 0.62-0.99，分别；交互作用P值=0.79），无论是否伴有心力衰竭（342人中有64人vs 336人中有79人）或不伴有心力衰竭（1,424人中有163人vs 1,430人中有200人）（HR: 0.75; 95% CI: 0.54-1.05; 和 HR: 0.81; 95% CI: 0.66-0.99，分别；交互作用P值=0.74），以及无论是否伴有高心血管疾病总体风险（675人中有73人vs 654人中有98人）或不伴有高心血管疾病总体风险（331人中有23人vs 340人中有28人）（HR: 0.71; 95% CI: 0.52-0.95; 和 HR: 0.82; 95% CI: 0.47-1.43，分别；交互作用P值=0.63）。

Conclusions

Semaglutide improved kidney and survival outcomes in type 2 diabetes with CKD, irrespective of established ASCVD, heart failure, or high total cardiovascular disease risk.

Semaglutide改善了2型糖尿病合并慢性肾脏病患者的肾脏和生存结果，无论是否存在已建立的动脉粥样硬化性心血管疾病(ASCVD)、心力衰竭或高心血管疾病总体风险。

(Evaluate Renal Function with Semaglutide Once Weekly [FLOW]; NCT03819153).

（每周一次Semaglutide评估肾功能[FLOW]；NCT03819153）。