The effects of canagliflozin in type 2 diabetes in subgroups defined by population‐specific body mass index: Insights from the CANVAS Program and CREDENCE trial

Abstract Aim 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. Methods 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. Results 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 heterogeneity = 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 heterogeneity = 0.72). The effects of canagliflozin on body weight and SBP differed across BMI subgroups ( P heterogeneity <0.01 and 0.04, respectively) but were consistent for albuminuria ( P heterogeneity = 0.60). Chronic eGFR slope with canagliflozin treatment was consistent across subgroups ( P heterogeneity >0.95). Conclusions 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.