Tu N Nguyen, Jie Yu, Vlado Perkovic, Meg Jardine, Kenneth W Mahaffey, Clara K Chow, Clare Arnott, Richard I Lindley
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Cox proportional-hazard models were used to estimate the efficacy and safety of canagliflozin overall and according to frailty status.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusions: </strong>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><p><strong>Trial registration: </strong>ClinicalTrials.gov CANVAS: NCT01032629; CANVAS-R: NCT01989754; CREDENCE: NCT02065791.</p>","PeriodicalId":94112,"journal":{"name":"Journal of the American Geriatrics Society","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"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\":\"<p><strong>Background: </strong>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><p><strong>Methods: </strong>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><p><strong>Results: </strong>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).</p><p><strong>Conclusions: </strong>Canagliflozin improved cardiovascular and mortality endpoints in participants with type 2 diabetes irrespective of frailty status, with a similar safety profile. 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引用次数: 0
摘要
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。
The Efficacy and Safety of Canagliflozin by Frailty Status in Participants of the CANVAS and CREDENCE Trials.
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.
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