Affiliation:
1. Cardiovascular Program The George Institute of Global Health, University of New South Wales Sydney Australia
2. Sydney Medical School, University of Sydney Sydney Australia
3. Department of Endocrinology and Diabetes Westmead Hospital Sydney Australia
4. Department of Renal Medicine Royal North Shore Hospital Sydney Australia
5. Department of Cardiology Royal Prince Alfred Hospital Sydney Australia
Abstract
AbstractAimsTo provide an overview of the primary outcomes and key clinical implications of the CANVAS Program and CREDENCE trial, which were event‐driven, double‐blind randomized controlled trials that established the efficacy and safety of canagliflozin in those with type 2 diabetes (T2D) and high cardiovascular risk (CV) or albuminuric chronic kidney disease (CKD).Methods and ResultsThe CANVAS programme (CANVAS and CANVAS‐R trials) randomized 10 142 people with T2D and high CV risk to canagliflozin or placebo and followed them for a median of 126 weeks. The primary efficacy outcome was met, with canagliflozin treatment associated with a 14% reduction in major adverse CV events (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.75 to 0.97; p < 0.001) as compared to placebo. The CREDENCE trial randomized 4401 individuals with T2D and albuminuric CKD to canagliflozin or placebo and followed them for 109 weeks. The CREDENCE trial also met its primary endpoint; canagliflozin treatment was associated with a 30% reduction in the composite of kidney failure, sustained doubling of serum creatinine level, or death from kidney or CV causes (HR 0.70, 95% CI 0.59 to 0.82; p < 0.001). Substantial reductions in hospitalization for heart failure (CANVAS: HR 0.67, 95% CI 0.52 to 0.87; CREDENCE: HR 0.61, 95% CI 0.47 to 0.80) and other key CV and kidney outcomes were also identified. Relative clinical benefits were consistent across subgroups defined by baseline age, sex, kidney function and history of CV disease but absolute benefits were greatest in those at highest baseline risk. Total serious adverse events were less common with canagliflozin treatment. Concerns about amputation and fracture risk observed in the CANVAS Program were not seen in CREDENCE and appear to have been spurious chance findings.ConclusionCanagliflozin reduced important CV, kidney and mortality outcomes in those with T2D and high CV risk or CKD across diverse patient groups, with a good safety profile. Taken together with the other sodium‐glucose cotransporter‐2 inhibitor CV and renal outcomes trials, these landmark findings have changed the treatment landscape for patients worldwide.