The Efficacy and Safety of Canagliflozin by Frailty Status in Participants of the CANVAS and CREDENCE Trials

IF 4.5 2区医学 Q1 GERIATRICS & GERONTOLOGY

Journal of the American Geriatrics Society Pub Date : 2025-03-19 DOI:10.1111/jgs.19444

Tu N. Nguyen, Jie Yu, Vlado Perkovic, Meg Jardine, Kenneth W. Mahaffey, Clara K. Chow, Clare Arnott, Richard I. Lindley

{"title":"The Efficacy and Safety of Canagliflozin by Frailty Status in Participants of the CANVAS and CREDENCE Trials","authors":"Tu N. Nguyen, Jie Yu, Vlado Perkovic, Meg Jardine, Kenneth W. Mahaffey, Clara K. Chow, Clare Arnott, Richard I. Lindley","doi":"10.1111/jgs.19444","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Background</h3>\n \n <p>Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to improve renal and cardiovascular outcomes in patients with type 2 diabetes. Limited evidence exists about the efficacy and safety of SGLT2 inhibitors in patients with frailty.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>This was a post hoc pooled, participant-level data analysis of the CANVAS Program (CANVAS and CANVAS-R) and the CREDENCE trial. We examined the effect of canagliflozin on: (1) Major adverse cardiovascular events (MACE), (2) Cardiovascular mortality, (3) all-cause mortality, and (4) key safety outcomes. Frailty was defined by a Frailty Index (FI) based on a deficit accumulation approach (FI > 0.25: frail). Cox proportional-hazard models were used to estimate the efficacy and safety of canagliflozin overall and according to frailty status.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>There were 14,543 participants (10,142 from the CANVAS Program, 4401 from the CREDENCE trial). Their mean age was 63.2 years; 35.3% were female. Frailty was present in 56% of the study participants. The benefits of canagliflozin were observed in both the frail and non-frail subgroups: HRs for MACE 0.80 (95% CI 0.70–0.90) in the frail versus 0.91 (95% CI 0.75–1.09) in the non-frail (<i>p</i> for interaction = 0.27); HRs for cardiovascular mortality 0.79 (95% CI 0.67–0.95) in the frail versus 0.94 (95% CI 0.70–1.27) in the non-frail (<i>p</i> for interaction = 0.38); HRs for all-cause mortality 0.81 (95% CI 0.70–0.94) in the frail versus 0.93 (95% CI 0.74–1.16) in the non-frail (<i>p</i> for interaction = 0.39). Adverse events were similar among frail and non-frail participants, except for osmotic diuresis (HRs 1.67, 95% CI 1.22–2.28 in the frail vs. 3.05, 95% CI 2.13–4.35 in the non-frail, p for interaction = 0.01).</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>Canagliflozin improved cardiovascular and mortality endpoints in participants with type 2 diabetes irrespective of frailty status, with a similar safety profile. Our findings, in addition to those from other recent studies, provide evidence to support the introduction of SGLT2 inhibitor therapy in patients perceived to be frail.</p>\n \n <p>\n <b>Trial Registration:</b> ClinicalTrials.gov CANVAS: NCT01032629; CANVAS-R: NCT01989754; CREDENCE: NCT02065791</p>\n </section>\n </div>","PeriodicalId":17240,"journal":{"name":"Journal of the American Geriatrics Society","volume":"73 6","pages":"1787-1796"},"PeriodicalIF":4.5000,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jgs.19444","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of the American Geriatrics Society","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/jgs.19444","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GERIATRICS & GERONTOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to improve renal and cardiovascular outcomes in patients with type 2 diabetes. Limited evidence exists about the efficacy and safety of SGLT2 inhibitors in patients with frailty.

Methods

This was a post hoc pooled, participant-level data analysis of the CANVAS Program (CANVAS and CANVAS-R) and the CREDENCE trial. We examined the effect of canagliflozin on: (1) Major adverse cardiovascular events (MACE), (2) Cardiovascular mortality, (3) all-cause mortality, and (4) key safety outcomes. Frailty was defined by a Frailty Index (FI) based on a deficit accumulation approach (FI > 0.25: frail). Cox proportional-hazard models were used to estimate the efficacy and safety of canagliflozin overall and according to frailty status.

Results

There were 14,543 participants (10,142 from the CANVAS Program, 4401 from the CREDENCE trial). Their mean age was 63.2 years; 35.3% were female. Frailty was present in 56% of the study participants. The benefits of canagliflozin were observed in both the frail and non-frail subgroups: HRs for MACE 0.80 (95% CI 0.70–0.90) in the frail versus 0.91 (95% CI 0.75–1.09) in the non-frail (p for interaction = 0.27); HRs for cardiovascular mortality 0.79 (95% CI 0.67–0.95) in the frail versus 0.94 (95% CI 0.70–1.27) in the non-frail (p for interaction = 0.38); HRs for all-cause mortality 0.81 (95% CI 0.70–0.94) in the frail versus 0.93 (95% CI 0.74–1.16) in the non-frail (p for interaction = 0.39). Adverse events were similar among frail and non-frail participants, except for osmotic diuresis (HRs 1.67, 95% CI 1.22–2.28 in the frail vs. 3.05, 95% CI 2.13–4.35 in the non-frail, p for interaction = 0.01).

Conclusions

Canagliflozin improved cardiovascular and mortality endpoints in participants with type 2 diabetes irrespective of frailty status, with a similar safety profile. Our findings, in addition to those from other recent studies, provide evidence to support the introduction of SGLT2 inhibitor therapy in patients perceived to be frail.

Trial Registration: ClinicalTrials.gov CANVAS: NCT01032629; CANVAS-R: NCT01989754; CREDENCE: NCT02065791

Abstract Image

查看原文本刊更多论文

canag列净在CANVAS和CREDENCE试验参与者中衰弱状态的有效性和安全性。

背景：钠-葡萄糖共转运蛋白2 （SGLT2）抑制剂已被证明可改善2型糖尿病患者的肾脏和心血管预后。关于SGLT2抑制剂在虚弱患者中的有效性和安全性的证据有限。方法：这是一项针对CANVAS项目（CANVAS和CANVAS- r）和CREDENCE试验的事后汇总、参与者水平的数据分析。我们检查了卡格列净对以下方面的影响：(1)主要不良心血管事件（MACE），(2)心血管死亡率，(3)全因死亡率，(4)关键安全性结局。虚弱是由基于赤字积累法的虚弱指数（FI）来定义的（FI > 0.25：虚弱）。采用Cox比例风险模型评估卡格列净的总体疗效和安全性，并根据虚弱状态进行评估。结果：14543名参与者（10142名来自CANVAS项目，4401名来自CREDENCE试验）。平均年龄63.2岁；35.3%为女性。56%的研究参与者身体虚弱。canagliflozin在虚弱和非虚弱亚组中均观察到益处：虚弱组的MACE hr为0.80 (95% CI 0.70-0.90)，而非虚弱组的MACE hr为0.91 (95% CI 0.75-1.09)（相互作用p = 0.27）；体弱者心血管死亡率的hr为0.79 (95% CI 0.67-0.95)，非体弱者为0.94 (95% CI 0.70-1.27)（相互作用p = 0.38）；体弱者全因死亡率的hr为0.81 (95% CI 0.70-0.94)，非体弱者为0.93 (95% CI 0.74-1.16)（相互作用p = 0.39）。不良事件在虚弱和非虚弱的参与者中相似，除了渗透性利尿（虚弱者的hr为1.67,95% CI为1.22-2.28，非虚弱者的hr为3.05,95% CI为2.13-4.35，相互作用p = 0.01）。结论：canag列净改善了2型糖尿病患者的心血管和死亡率终点，与虚弱状态无关，具有相似的安全性。我们的研究结果，加上其他近期研究的结果，提供了支持在虚弱患者中引入SGLT2抑制剂治疗的证据。试验注册：ClinicalTrials.gov CANVAS: NCT01032629；CANVAS-R: NCT01989754;信任:NCT02065791。

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

Journal of the American Geriatrics Society 医学-老年医学

CiteScore

10.00

自引率

6.30%

发文量

504

审稿时长

3-6 weeks

期刊介绍： Journal of the American Geriatrics Society (JAGS) is the go-to journal for clinical aging research. We provide a diverse, interprofessional community of healthcare professionals with the latest insights on geriatrics education, clinical practice, and public policy—all supporting the high-quality, person-centered care essential to our well-being as we age. Since the publication of our first edition in 1953, JAGS has remained one of the oldest and most impactful journals dedicated exclusively to gerontology and geriatrics.