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

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 compos-ite renal outcomes (HR 0.75, 95% CI 0.66 to 0.84) with no heterogeneity across sub-groups observed (Pheterogeneity = 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 pro-file were consistent across population-specific BMI subgroups for adults in the CAN -VAS Program and CREDENCE trial.

Automated summary

This study assessed the effects of canagliflozin on clinical outcomes and intermediate markers in patients with different BMI categories. The findings showed that canagliflozin reduced the risk of major adverse cardiovascular events and renal outcomes, with no differences in treatment effect across BMI subgroups. However, the effects of canagliflozin on body weight and blood pressure varied among different BMI subgroups.