Canagliflozin consistently effective for patients of different age groups with diabetic kidney disease

In addition, the absolute reduction in adverse kidney outcomes was more significant in younger participants owing to higher background risk.

There has been no clarity on canagliflozin's effect on adverse cardiovascular and kidney events in people with diabetic kidney disease varies by sex and age. Therefore, Tae Won Yi, University of New South Wales, Sydney, Australia, and colleagues investigated the effects of canagliflozin between sexes and among age group categories in a post hoc analysis of the CREDENCE Randomized Clinical Trial.

The study included 4,401 patients with type 2 diabetes and albuminuric chronic kidney disease (CKD) for a secondary analysis of the randomized controlled CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) trial. Participants were followed for a median of 2.62 years.

Patients were randomly allocated to receive either 100 mg of canagliflozin daily or a placebo. The composite of kidney failure, death due to cardiovascular or kidney disease, and doubling serum creatinine was considered the primary outcome.

The investigators measured the outcome by sex and age at baseline in the intention-to-treat population using Cox regression models. They specifically aimed to determine if canagliflozin was safe and effective for women and men, patients aged at least 70, between 60 and 69, and patients younger than 60. The cohort's mean age was 63.0±9.2 years, and 34% were female.

The study led to the following findings:

• Female sex and older age were independently associated with a lower risk of the composite of adverse kidney outcomes.
• The researchers did not find any evidence that canagliflozin's effect on the primary outcome (a composite of kidney failure, death from kidney or cardiovascular causes, or a doubling of the serum creatinine) differed among females and males (HR 0.71 and HR 0.69, respectively); or between age groups (HR 0.67; HR 0.63; and HR 0.89; for the <60, 60-69, and ≥ 70-year groups, respectively).
• The authors did not observe any differences in safety outcomes by sex or age group.

Data from the CREDENCE trial suggest that canagliflozin consistently lowered the relative risk of kidney events in patients with diabetic kidney disease across age subgroups and both sexes. The absolute benefit of canagliflozin was more significant in younger participants at higher risk of adverse kidney outcomes.

"These results should help clarify decision-making for patients with diabetes and chronic kidney disease," the authors concluded.

Reference:

Yi TW, Smyth B, Di Tanna GL, Arnott C, Cardoza K, Kang A, Pollock C, Agarwal R, Bakris G, Charytan DM, de Zeeuw D, Heerspink HJL, Neal B, Wheeler DC, Cannon CP, Zhang H, Zinman B, Perkovic V, Levin A, Mahaffey KW, Jardine M; CREDENCE Trial Investigators. Kidney and Cardiovascular Effects of Canagliflozin According to Age and Sex: A Post Hoc Analysis of the CREDENCE Randomized Clinical Trial. Am J Kidney Dis. 2023 Mar 6:S0272-6386(23)00537-1. doi: 10.1053/j.ajkd.2022.12.015. Epub ahead of print. PMID: 36889425.