Even in Advanced CKD, Canaglifozin Slows Rate of Kidney Decline, Study Says

A new analysis of the sodium-glucose cotransporter 2 (SGLT2) inhibitor canagliflozin showed that it slowed the decline of kidney function in patients with type 2 diabetes (T2D) and advanced chronic kidney disease (CKD) by 66%, and also reduced the risk of developing kidney failure and cardiovascular problems.

That is an even larger effect than the original 2019 study results of the drug on less severe disease.

The landmark CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) trial documented the effects of canagliflozin in patients with diabetes and kidney disease, including the future risk of cardiovascular events. The 2019 results for canagliflozin (Invokana, sold by Janssen) showed a 30% risk reduction in renal decline and cardiovascular and renal death among patients with T2D.

Based on those results, the FDA approved canaglifozin for the prevention of kidney failure in patients with T2D with diabetes with an estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m².

However, until now, it hasn’t been clear what the effect of canaglifozin would be on patients with advanced, stage 4 or stage 5 CKD. By that point, most patients are simply monitored or are prepared to start receiving dialysis or to undergo kidney transplant surgery.

The effect of SGLT2s are believed to be less powerful with reduced glomerular filtration. But the need for improved treatment for advanced disease is huge: kidney failure is one of the most expensive and debilitating conditions in Medicare—and so costly that once patients need dialysis, they quickly become eligible for Medicare regardless of age. According to the National Kidney Foundation, 37 million people in the United States have kidney disease, which can result from diabetes.

This post hoc analysis, published Thursday in CJASN, evaluated patients with an eGFR below 30 mL/min/1.73 m² at the start of the trial and at randomization to receive either 100 mg of canagliflozin or a placebo.

Four percent (174) of the 4401 participants in the CREDENCE trial fell into this group; they received the maximum labeled or tolerated dose of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker for ≥4 weeks prior to randomization.

The median follow up was 2.62 years. The mean rate of decline in eGFR was 66% lower (–1.30 vs –3.83 ml/min/1.73m²/year) in the canagliflozin group while the albumin-to-creatinine ratio (ACR) was 33% lower (95% CI, 10%-49%) in the canagliflozin group.

The incidence of AKI was no different between the 2 groups. Moreover, there was no acute reversible decline in eGFR.

References

Bakris G, Oshima M, Mahaffey KW, et al. Effects of canagliflozin in patients with baseline eGFR <30 mL/min/1.73 m2: Subgroup analysis of the randomized CREDENCE trial. Clin J Am Soc Nephrol. Published online November 19, 2020. doi: 10.2215/CJN.10140620.