在CANVAS和CREDENCE试验参与者中，按虚弱状态划分的卡格列净的疗效和安全性
The Efficacy and Safety of Canagliflozin by Frailty Status in Participants of the CANVAS and CREDENCE Trials.
作者信息
Nguyen Tu N, Yu Jie, Perkovic Vlado, Jardine Meg, Mahaffey Kenneth W, Chow Clara K, Arnott Clare, Lindley Richard I
机构信息
Westmead Applied Research Centre, Sydney Medical School, Faculty of Medicine and Health, University of Sydney, Sydney, New South Wales, Australia.
The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia.
出版信息
J Am Geriatr Soc. 2025 Jun;73(6):1787-1796. doi: 10.1111/jgs.19444. Epub 2025 Mar 19.
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.
背景
钠-葡萄糖协同转运蛋白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结局。关于SGLT2抑制剂在虚弱患者中的疗效和安全性的证据有限。
方法
这是一项对CANVAS项目（CANVAS和CANVAS-R）和CREDENCE试验进行的事后汇总、参与者水平的数据分析。我们研究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，以及（4）关键安全性结局。虚弱通过基于缺陷积累方法的虚弱指数（FI）来定义（FI>0.25：虚弱）。使用Cox比例风险模型来估计卡格列净总体以及根据虚弱状态的疗效和安全性。
结果
共有14543名参与者（CANVAS项目中有10142名，CREDENCE试验中有4401名）。他们的平均年龄为63.2岁；35.3%为女性。56%的研究参与者存在虚弱。在虚弱和非虚弱亚组中均观察到了卡格列净的益处：虚弱亚组中MACE的风险比（HR）为0.80（95%置信区间[CI]0.70 - 0.90），非虚弱亚组中为0.91（95%CI0.75 - 1.09）（交互作用p值 = 0.27）；虚弱亚组中心血管死亡率的HR为0.79（95%CI0.67 - 0.95），非虚弱亚组中为0.94（95%CI0.70 - 1.27）（交互作用p值 = 0.38）；全因死亡率的HR在虚弱亚组中为0.81（95%CI0.70 - 0.94），非虚弱亚组中为0.93（95%CI0.74 - 1.16）（交互作用p值 = 0.39）。除渗透性利尿外，虚弱和非虚弱参与者的不良事件相似（虚弱亚组中HR为1.67，95%CI1.22 - 2.28，非虚弱亚组中为3.05，95%CI2.13 - 4.35，交互作用p值 = 0.01）。
结论
无论虚弱状态如何，卡格列净均可改善2型糖尿病参与者的心血管和死亡率终点，且安全性特征相似。我们的研究结果以及近期其他研究的结果为支持在被认为虚弱的患者中引入SGLT2抑制剂治疗提供了证据。
试验注册
ClinicalTrials.gov上CANVAS的注册号：NCT01032629；CANVAS-R：NCT01989754；CREDENCE：NCT02065791。
Zotero 插件