Peter Rossing, George Bakris, Vlado Perkovic, Richard Pratley, Katherine R Tuttle, Kenneth W Mahaffey, Thomas Idorn, Nicolas Belmar, Heidrun Bosch-Traberg, Søren Rasmussen, Robert S Busch, Ronald E Schmieder, Pieter Gillard, Johannes F E Mann
{"title":"西马鲁肽联合或不联合矿皮质激素受体拮抗剂对2型糖尿病和慢性肾病患者的影响：一项预先指定的流量试验二次分析","authors":"Peter Rossing, George Bakris, Vlado Perkovic, Richard Pratley, Katherine R Tuttle, Kenneth W Mahaffey, Thomas Idorn, Nicolas Belmar, Heidrun Bosch-Traberg, Søren Rasmussen, Robert S Busch, Ronald E Schmieder, Pieter Gillard, Johannes F E Mann","doi":"10.2337/dc25-0472","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>In the Evaluate Renal Function With Semaglutide Once Weekly (FLOW) trial, semaglutide reduced the risk of major kidney and cardiovascular (CV) outcomes and all-cause mortality in people with type 2 diabetes (T2D) and chronic kidney disease (CKD). This prespecified analysis assessed the effects of semaglutide on kidney, CV, and mortality outcomes by baseline mineralocorticoid receptor antagonist (MRA) use.</p><p><strong>Research design and methods: </strong>Participants were randomized to once-weekly subcutaneous semaglutide 1.0 mg or placebo. The primary kidney outcome was a composite of time to first persistent ≥50% eGFR reduction from baseline, kidney failure, or death from kidney/CV causes. Baseline MRA was predominantly spironolactone; finerenone was only available after recruitment ended.</p><p><strong>Results: </strong>Effects were analyzed by baseline MRA use (n = 257 [136 in the semaglutide group and 121 in the placebo group]) and nonuse (n = 3,276 [1,631 in the semaglutide group and 1,645 in the placebo group]). Semaglutide reduced the risk of the primary kidney outcome by 49% (59 events; hazard ratio [HR] 0.51 [95% CI 0.30, 0.86]) and 21% (682 events; HR 0.79 [95% CI 0.68, 0.92]; P-interaction = 0.12) versus placebo in MRA and non-MRA subgroups, respectively. There was no heterogeneity, favoring the effects of semaglutide on major adverse CV events (MACE) and all-cause mortality in both MRA subgroups (P-interaction > 0.7). Albuminuria at 104 weeks was reduced from baseline with semaglutide by 15% (95% CI -41, 31) in MRA users and 33% (26, 39) in nonusers versus placebo (P-interaction = 0.22). Estimated glomerular filtration rate decline was similarly reduced with semaglutide (P-interaction = 0.71). The safety profile of semaglutide was comparable between subgroups.</p><p><strong>Conclusions: </strong>In participants with T2D and CKD, consistent benefits of semaglutide on major kidney outcomes, MACE, and all-cause mortality were observed regardless of baseline MRA use.</p>","PeriodicalId":93979,"journal":{"name":"Diabetes care","volume":" ","pages":""},"PeriodicalIF":16.6000,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Effects of Semaglutide With or Without Concomitant Mineralocorticoid Receptor Antagonist Use in Participants With Type 2 Diabetes and Chronic Kidney Disease: A FLOW Trial Prespecified Secondary Analysis.\",\"authors\":\"Peter Rossing, George Bakris, Vlado Perkovic, Richard Pratley, Katherine R Tuttle, Kenneth W Mahaffey, Thomas Idorn, Nicolas Belmar, Heidrun Bosch-Traberg, Søren Rasmussen, Robert S Busch, Ronald E Schmieder, Pieter Gillard, Johannes F E Mann\",\"doi\":\"10.2337/dc25-0472\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>In the Evaluate Renal Function With Semaglutide Once Weekly (FLOW) trial, semaglutide reduced the risk of major kidney and cardiovascular (CV) outcomes and all-cause mortality in people with type 2 diabetes (T2D) and chronic kidney disease (CKD). This prespecified analysis assessed the effects of semaglutide on kidney, CV, and mortality outcomes by baseline mineralocorticoid receptor antagonist (MRA) use.</p><p><strong>Research design and methods: </strong>Participants were randomized to once-weekly subcutaneous semaglutide 1.0 mg or placebo. The primary kidney outcome was a composite of time to first persistent ≥50% eGFR reduction from baseline, kidney failure, or death from kidney/CV causes. Baseline MRA was predominantly spironolactone; finerenone was only available after recruitment ended.</p><p><strong>Results: </strong>Effects were analyzed by baseline MRA use (n = 257 [136 in the semaglutide group and 121 in the placebo group]) and nonuse (n = 3,276 [1,631 in the semaglutide group and 1,645 in the placebo group]). Semaglutide reduced the risk of the primary kidney outcome by 49% (59 events; hazard ratio [HR] 0.51 [95% CI 0.30, 0.86]) and 21% (682 events; HR 0.79 [95% CI 0.68, 0.92]; P-interaction = 0.12) versus placebo in MRA and non-MRA subgroups, respectively. There was no heterogeneity, favoring the effects of semaglutide on major adverse CV events (MACE) and all-cause mortality in both MRA subgroups (P-interaction > 0.7). Albuminuria at 104 weeks was reduced from baseline with semaglutide by 15% (95% CI -41, 31) in MRA users and 33% (26, 39) in nonusers versus placebo (P-interaction = 0.22). Estimated glomerular filtration rate decline was similarly reduced with semaglutide (P-interaction = 0.71). 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引用次数: 0
摘要
目的：在西马鲁肽评估肾功能每周一次（FLOW）试验中，西马鲁肽降低了2型糖尿病（T2D）和慢性肾脏疾病（CKD）患者主要肾脏和心血管（CV）结局和全因死亡率的风险。这项预先指定的分析评估了西马鲁肽对肾脏、心血管和死亡率结果的影响，通过基线矿皮质激素受体拮抗剂（MRA）的使用。研究设计和方法：参与者随机接受每周一次皮下注射西马鲁肽1.0 mg或安慰剂治疗。肾脏的主要结局是首次持续eGFR较基线降低≥50%的时间，肾功能衰竭或肾脏/CV原因导致的死亡。基线MRA主要是螺内酯；Finerenone只有在招募结束后才能使用。结果：通过基线MRA使用（n = 257 [semaglutide组136人，安慰剂组121人]）和未使用（n = 3276 [semaglutide组1631人，安慰剂组1645人]）来分析疗效。Semaglutide将原发性肾脏结局的风险降低了49%(59个事件；风险比[HR] 0.51 [95% CI 0.30, 0.86])和21%(682件事件；Hr 0.79 [95% ci 0.68, 0.92]；p交互作用= 0.12)与安慰剂相比，分别在MRA和非MRA亚组中。在两个MRA亚组中，没有异质性，支持西马鲁肽对主要不良CV事件（MACE）和全因死亡率的影响（p -相互作用>.7）。与安慰剂相比，使用semaglutide治疗104周时，MRA使用者的蛋白尿比基线减少15% (95% CI - 41,31)，未使用MRA者减少33% (26,39)（p相互作用= 0.22）。估计的肾小球滤过率下降与西马鲁肽相似（p相互作用= 0.71）。西马鲁肽的安全性在亚组间具有可比性。结论：在患有T2D和CKD的参与者中，无论基线MRA使用情况如何，都观察到西马鲁肽对主要肾脏结局、MACE和全因死亡率的一致益处。
Effects of Semaglutide With or Without Concomitant Mineralocorticoid Receptor Antagonist Use in Participants With Type 2 Diabetes and Chronic Kidney Disease: A FLOW Trial Prespecified Secondary Analysis.
Objective: In the Evaluate Renal Function With Semaglutide Once Weekly (FLOW) trial, semaglutide reduced the risk of major kidney and cardiovascular (CV) outcomes and all-cause mortality in people with type 2 diabetes (T2D) and chronic kidney disease (CKD). This prespecified analysis assessed the effects of semaglutide on kidney, CV, and mortality outcomes by baseline mineralocorticoid receptor antagonist (MRA) use.
Research design and methods: Participants were randomized to once-weekly subcutaneous semaglutide 1.0 mg or placebo. The primary kidney outcome was a composite of time to first persistent ≥50% eGFR reduction from baseline, kidney failure, or death from kidney/CV causes. Baseline MRA was predominantly spironolactone; finerenone was only available after recruitment ended.
Results: Effects were analyzed by baseline MRA use (n = 257 [136 in the semaglutide group and 121 in the placebo group]) and nonuse (n = 3,276 [1,631 in the semaglutide group and 1,645 in the placebo group]). Semaglutide reduced the risk of the primary kidney outcome by 49% (59 events; hazard ratio [HR] 0.51 [95% CI 0.30, 0.86]) and 21% (682 events; HR 0.79 [95% CI 0.68, 0.92]; P-interaction = 0.12) versus placebo in MRA and non-MRA subgroups, respectively. There was no heterogeneity, favoring the effects of semaglutide on major adverse CV events (MACE) and all-cause mortality in both MRA subgroups (P-interaction > 0.7). Albuminuria at 104 weeks was reduced from baseline with semaglutide by 15% (95% CI -41, 31) in MRA users and 33% (26, 39) in nonusers versus placebo (P-interaction = 0.22). Estimated glomerular filtration rate decline was similarly reduced with semaglutide (P-interaction = 0.71). The safety profile of semaglutide was comparable between subgroups.
Conclusions: In participants with T2D and CKD, consistent benefits of semaglutide on major kidney outcomes, MACE, and all-cause mortality were observed regardless of baseline MRA use.
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