Oral Semaglutide and Cardiovascular Outcomes in People With Type 2 Diabetes, According to SGLT2i Use: Prespecified Analyses of the SOUL Randomized Trial.

IF 38.6 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

Circulation Pub Date : 2025-06-10 Epub Date: 2025-03-29 DOI:10.1161/CIRCULATIONAHA.125.074545

Nikolaus Marx, John E Deanfield, Johannes F E Mann, Rosario Arechavaleta, Stephen C Bain, Harpreet S Bajaj, Katrine Bayer Tanggaard, Andreas L Birkenfeld, John B Buse, Zaklina Davicevic-Elez, Cyrus Desouza, Scott S Emerson, Mads D M Engelmann, G Kees Hovingh, Silvio E Inzucchi, Pardeep S Jhund, Sharon L Mulvagh, Rodica Pop-Busui, Neil R Poulter, Søren Rasmussen, Shih-Te Tu, Darren K McGuire

{"title":"Oral Semaglutide and Cardiovascular Outcomes in People With Type 2 Diabetes, According to SGLT2i Use: Prespecified Analyses of the SOUL Randomized Trial.","authors":"Nikolaus Marx, John E Deanfield, Johannes F E Mann, Rosario Arechavaleta, Stephen C Bain, Harpreet S Bajaj, Katrine Bayer Tanggaard, Andreas L Birkenfeld, John B Buse, Zaklina Davicevic-Elez, Cyrus Desouza, Scott S Emerson, Mads D M Engelmann, G Kees Hovingh, Silvio E Inzucchi, Pardeep S Jhund, Sharon L Mulvagh, Rodica Pop-Busui, Neil R Poulter, Søren Rasmussen, Shih-Te Tu, Darren K McGuire","doi":"10.1161/CIRCULATIONAHA.125.074545","DOIUrl":null,"url":null,"abstract":"Background: Both GLP-1 (glucagon-like peptide-1) receptor agonists and SGLT2 (sodium-glucose cotransporter-2) inhibitors (SGLT2i) improve cardiovascular outcomes in people with type 2 diabetes and cardiovascular or chronic kidney disease. However, there are limited data about the effect of combining these agents on cardiovascular and safety outcomes.Methods: The SOUL trial (Semaglutide Cardiovascular Outcomes Trial; NCT03914326) randomized 9650 participants with type 2 diabetes and atherosclerotic cardiovascular disease and/or chronic kidney disease to oral semaglutide or placebo. As prespecified, participants were analyzed according to baseline use of SGLT2i (yes, n=2596; no, n=7054), and subsequently for any use of SGLT2i during the trial (yes, n=4718; no, n=4932). The primary outcome was time to first major adverse cardiovascular event, defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Safety was evaluated by comparing the incidence of serious adverse events.Results: Over a mean follow-up of 47.5±10.9 months, the risk of the primary outcome in the overall trial population was 14% lower for oral semaglutide versus placebo (hazard ratio, 0.86; 95% CI, 0.77-0.96). In those taking SGLT2i at baseline, there were 143 of 1296 (semaglutide) versus 158 of 1300 (placebo) primary outcome events (hazard ratio, 0.89; 95% CI, 0.71-1.11); and 436 of 3529 versus 510 of 3525, respectively, in participants not taking SGLT2i at baseline (hazard ratio, 0.84; 95% CI, 0.74-0.95; P-interaction, 0.66). An analysis of major adverse cardiovascular events by any in-trial SGLT2i use versus no use also showed no evidence of heterogeneity in the effects of oral semaglutide. The adverse event profiles of oral semaglutide with or without concomitant SGLT2i were similar.Conclusions: Oral semaglutide reduced major adverse cardiovascular event outcomes independently of concomitant SGLT2i treatment, and this combination appeared to be safe.Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03914326.","PeriodicalId":10331,"journal":{"name":"Circulation","volume":" ","pages":"1639-1650"},"PeriodicalIF":38.6000,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12144549/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Circulation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1161/CIRCULATIONAHA.125.074545","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/3/29 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"CARDIAC & CARDIOVASCULAR SYSTEMS","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Both GLP-1 (glucagon-like peptide-1) receptor agonists and SGLT2 (sodium-glucose cotransporter-2) inhibitors (SGLT2i) improve cardiovascular outcomes in people with type 2 diabetes and cardiovascular or chronic kidney disease. However, there are limited data about the effect of combining these agents on cardiovascular and safety outcomes.

Methods: The SOUL trial (Semaglutide Cardiovascular Outcomes Trial; NCT03914326) randomized 9650 participants with type 2 diabetes and atherosclerotic cardiovascular disease and/or chronic kidney disease to oral semaglutide or placebo. As prespecified, participants were analyzed according to baseline use of SGLT2i (yes, n=2596; no, n=7054), and subsequently for any use of SGLT2i during the trial (yes, n=4718; no, n=4932). The primary outcome was time to first major adverse cardiovascular event, defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Safety was evaluated by comparing the incidence of serious adverse events.

Results: Over a mean follow-up of 47.5±10.9 months, the risk of the primary outcome in the overall trial population was 14% lower for oral semaglutide versus placebo (hazard ratio, 0.86; 95% CI, 0.77-0.96). In those taking SGLT2i at baseline, there were 143 of 1296 (semaglutide) versus 158 of 1300 (placebo) primary outcome events (hazard ratio, 0.89; 95% CI, 0.71-1.11); and 436 of 3529 versus 510 of 3525, respectively, in participants not taking SGLT2i at baseline (hazard ratio, 0.84; 95% CI, 0.74-0.95; P-interaction, 0.66). An analysis of major adverse cardiovascular events by any in-trial SGLT2i use versus no use also showed no evidence of heterogeneity in the effects of oral semaglutide. The adverse event profiles of oral semaglutide with or without concomitant SGLT2i were similar.

Conclusions: Oral semaglutide reduced major adverse cardiovascular event outcomes independently of concomitant SGLT2i treatment, and this combination appeared to be safe.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03914326.

查看原文本刊更多论文

根据SGLT2i的使用，口服西马鲁肽和2型糖尿病患者的心血管结局：SOUL随机试验的预先指定分析

背景：胰高血糖素样肽-1受体激动剂（GLP-1 RA）和钠-葡萄糖共转运蛋白-2抑制剂（SGLT2i）均可改善2型糖尿病（T2D）和CV或慢性肾脏疾病（CKD）患者的心血管（CV）结局。然而，关于联合使用这些药物对CV和安全性结果的影响的数据有限。方法：SOUL试验（NCT03914326）将9650名T2D和动脉粥样硬化性CV疾病和/或CKD患者随机分为口服西马鲁肽或安慰剂组。按照预先规定，参与者根据SGLT2i的基线使用情况（是：n=2596，否：n=7054）进行分析，随后根据试验期间SGLT2i的任何使用情况（是：n=4718，否：n=4932）进行分析。主要终点是发生首次主要心血管不良事件（MACE）的时间，MACE定义为心血管死亡、非致死性心肌梗死或非致死性卒中。通过比较严重不良事件的发生率来评估安全性。结果：在平均47.5±10.9个月的随访中，在整个试验人群中，口服西马鲁肽与安慰剂的主要结局风险低14%(风险比[HR] 0.86, 95%可信区间[CI] 0.77；0.96)。在基线时服用SGLT2i的患者中，主要结局事件分别为143/1296（西马鲁肽）和158/1300（安慰剂）(HR 0.89；95% ci 0.71；1.11);基线时未服用SGLT2i的受试者分别为436/3529和510/3525 (HR 0.84；95% ci 0.74；0.95;P-interaction 0.66)。对试验中使用SGLT2i与未使用SGLT2i的MACE的分析也显示，没有证据表明口服西马鲁肽的效果存在异质性。口服西马鲁肽伴或不伴SGLT2i的不良事件概况相似。结论：口服semaglutide独立于SGLT2i治疗降低了MACE结果，并且这种联合治疗似乎是安全的。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Circulation 医学-外周血管病

CiteScore

45.70

自引率

2.10%

发文量

1473

审稿时长

2 months

期刊介绍： Circulation is a platform that publishes a diverse range of content related to cardiovascular health and disease. This includes original research manuscripts, review articles, and other contributions spanning observational studies, clinical trials, epidemiology, health services, outcomes studies, and advancements in basic and translational research. The journal serves as a vital resource for professionals and researchers in the field of cardiovascular health, providing a comprehensive platform for disseminating knowledge and fostering advancements in the understanding and management of cardiovascular issues.