The George Institute for Global Health, University of New South Wales, Sydney, Australia.
Faculty of Medicine, University of New South Wales, Sydney, Australia.
Diabetes Obes Metab. 2023 Dec;25(12):3724-3735. doi: 10.1111/dom.15267. Epub 2023 Sep 6.
To assess the effects of canagliflozin on clinical outcomes and intermediate markers across population-specific body mass index (BMI) categories in the CANVAS Program and CREDENCE trial.
Individual participant data were pooled and analysed in subgroups according to population-specific BMI. The main outcomes of interest were: major adverse cardiovascular events (MACE, a composite of nonfatal myocardial infarction, nonfatal stroke or cardiovascular death); composite renal outcome; and changes in systolic blood pressure (SBP), body weight, albuminuria and estimated glomerular filtration rate (eGFR) slope. Cox proportional hazards models and mixed-effect models were used.
A total of 14 520 participants were included, of whom 9378 (65%) had obesity. Overall, canagliflozin reduced the risk of MACE (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.75 to 0.93) with no heterogeneity of treatment effect across BMI subgroups (P = 0.76). Similarly, canagliflozin reduced composite renal outcomes (HR 0.75, 95% CI 0.66 to 0.84) with no heterogeneity across subgroups observed (P = 0.72). The effects of canagliflozin on body weight and SBP differed across BMI subgroups (P <0.01 and 0.04, respectively) but were consistent for albuminuria (P = 0.60). Chronic eGFR slope with canagliflozin treatment was consistent across subgroups (P >0.95).
The cardiovascular and renal benefits of canagliflozin and its safety profile were consistent across population-specific BMI subgroups for adults in the CANVAS Program and CREDENCE trial.
评估坎格列净在 CANVAS 项目和 CREDENCE 试验中特定人群体重指数（BMI）类别内对临床结局和中间标志物的影响。
根据特定人群的 BMI 对个体参与者数据进行分组汇总和分析。主要观察终点为：主要不良心血管事件（MACE，非致死性心肌梗死、非致死性卒中和心血管死亡的复合终点）；复合肾脏结局；收缩压（SBP）、体重、白蛋白尿和估算肾小球滤过率（eGFR）斜率的变化。采用 Cox 比例风险模型和混合效应模型进行分析。
共纳入 14520 名参与者，其中 9378 名（65%）患有肥胖症。总体而言，坎格列净降低了 MACE 的风险（风险比[HR]0.83，95%置信区间[CI]0.75 至 0.93），且在 BMI 亚组之间治疗效果无异质性（P = 0.76）。同样，坎格列净降低了复合肾脏结局（HR 0.75，95%CI 0.66 至 0.84），且在亚组间观察到无异质性（P = 0.72）。坎格列净对体重和 SBP 的影响在 BMI 亚组之间存在差异（P <0.01 和 0.04），但对白蛋白尿的影响一致（P = 0.60）。坎格列净治疗的慢性 eGFR 斜率在亚组间一致（P >0.95）。
在 CANVAS 项目和 CREDENCE 试验中，特定人群 BMI 亚组内，坎格列净的心血管和肾脏获益及其安全性特征一致。
