Kidney and Cardiovascular Effects of Canagliflozin According to Age and Sex: A Post Hoc Analysis of the CREDENCE Randomized Clinical Trial

Abstract

It is unclear whether the effect of canagliflozin on adverse kidney and cardiovascular events in those with diabetic kidney disease varies by age and sex. We assessed the effects of canagliflozin among age group categories and between sexes in the CREDENCE study. Secondary analysis of a randomized controlled trial. Participants in the CREDENCE trial. Participants were randomly assigned to canagliflozin 100 mg daily or placebo. Primary composite outcome of kidney failure, doubling of serum creatinine, or death due to kidney or cardiovascular disease. Pre-specified secondary and safety outcomes were also analyzed. Outcomes were evaluated by age at baseline (<60, 60-69, and ≥70 years) and sex in the intention-to-treat population using Cox regression models. The mean age of the cohort was 63.0±9.2 years and 34% were female. Older age and female sex were independently associated with a lower risk of the composite of adverse kidney outcomes. There was no evidence that the effect of canagliflozin on the primary outcome (a composite of kidney failure, a doubling of the serum creatinine, or death from kidney or cardiovascular causes) differed between age groups (HR 0.67, 95% CI 0.52 to 0.87; HR 0.63, 95% CI 0.48 to 0.82; and HR 0.89, 95% CI 0.61 to 1.29; for the <60, 60-69, and ≥70 year groups, respectively; Pinteraction=0.3); or among females and males (HR 0.71, 95% CI 0.54 to 0.95; and HR 0.69, 95% CI 0.56 to 0.84, respectively; Pinteraction=0.8). No differences in safety outcomes by age group or sex were observed. This was a post hoc analysis with multiple comparisons. Canagliflozin consistently reduced the relative risk of kidney events in people with diabetic kidney disease in both sexes and across age subgroups. Owing to higher background risk, the absolute reduction in adverse kidney outcomes was greater in younger participants.