Canagliflozin is estimated to delay time to dialysis by approximately 13 years, an analysis using CREDENCE trial data

On top of standard of care with ACE inhibitors or ARBs, the CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) trial showed that canagliflozin slowed down renal function decline and delays progression to end-stage kidney disease compared to placebo in patients with type 2 diabetes and chronic kidney disease. When individuals reach end-stage kidney disease, dialysis is the most common therapy required, which represents poor disease prognosis and poor quality of life. What does this slowing down of renal function decline mean in terms of delaying time to dialysis for patients?

The estimated glomerular filtration rate (eGFR) measures renal function and shows a linear decline over time. Differences in the rate (slope) of eGFR decline can be used to assess treatment effects on kidney function. Consistent with known renal hemodynamic effects of sodium-glucose cotransport 2 (SGLT2) inhibition, in the CREDENCE trial, canagliflozin treatment was associated with an acute drop in eGFR from baseline to week 3 followed by stablisation and slowing down of the decline vs. placebo from week 3 to the end of the study.

Delayed time to dialysis is modelled by:

• Utilising a linear projection of eGFR slopes reported for patients treated with canagliflozin or placebo in the CREDENCE trial
• Using mean eGFR over time calculated with acute (baseline to week 3) and chronic (week 3 onwards) slopes
• Assuming maintenance of stable therapy with canagliflozin
• Assuming reaching eGFR of 10 ml/min/1.73m2 represents the need for chronic dialysis

In this analysis using clinical trial data from CREDENCE with a median follow up of 2.62 years, canagliflozin treatment is projected to delay initiation of dialysis by approximately 12.95 (lower estimate 9.27, upper estimate 17.48) years relative to placebo.

Additionally, based on the average duration of dialysis and costs of dialysis in the US, the delay in dialysis with canagliflozin would be associated with a reduction in dialysis costs of approximately $170,000 per patient in 2020 dollars.

"For me the value of data like these is that it makes communicating the benefits of canagliflozin in Type 2 diabetes and Chronic Kidney Disease easier to the patients I see."

Dr. De Cosmo