Efficacy, Safety of Dapagliflozin in Stage 4 Chronic Kidney Disease

Dapagliflozin was shown to significantly reduce the risk of kidney failure and prolong survival in patients with advanced chronic kidney disease regardless of diabetes status.

Dapagliflozin (Farxiga; AstraZeneca) produced similar effects in patients with stage 4 chronic kidney disease (CKD) compared to those with mild-to-moderate kidney disease, according to a new analysis.

Studies have shown that sodium-glucose co-transporter 2 (SGLT2) inhibitors, such as dapagliflozin, can provide kidney- and cardiovascular-related benefits for individuals with or without diabetes and with or without impaired kidney function.1 The FDA approved dapagliflozin in May for use in patients with CKD at risk of progression.

For the pre-specified analysis, Glenn M. Chertow, MD, MPH, of Stanford University School of Medicine, and his colleagues examined data from the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial. This trial studied the effects of dapagliflozin on chronic kidney disease (CKD) in patients with varying health statuses. The study included patients with and without type 2 diabetes and mildly decreased to severely decreased kidney function, such as stage 4 CKD.

In the DAPA-CKD trial, 14% of patients had stage 4 CKD with an estimated glomerular filtration rate (eGFR) as low as 25 mL/min/1.73m2 at the beginning of the study. Patients were randomized to receive daily treatments of the SGLT2 inhibitor dapagliflozin or placebo. Those randomized to dapagliflozin experienced a 27% reduction in the primary end point (a composite of a sustained and large decline in kidney function, kidney failure, or death). Dapagliflozin-treated patients with stage 4 CKD also demonstrated a 29%, 17%, and 32% reduction in the kidney, cardiovascular, and mortality end points, respectively, compared with those randomized to placebo. The rates of adverse effects were similar in the 2 groups.1

The effects of dapagliflozin in patients with stage 4 CKD are similar to effects in patients with mild-to-moderate CKD, the investigators concluded.2Among patients with stage 4 CKD and albuminuria, dapagliflozin's benefits were consistent with those observed in the DAPA-CKD trial overall, with no evidence of increased risks.1

“While patients with screening eGFR as low as 25 mL/min/1.73m2 were enrolled, it is noteworthy that neither dapagliflozin nor placebo was discontinued when eGFR declined, even to below 15 mL/min/1.73m2,” Chertow said about the findings. “Therefore, a drug initially developed for the treatment of diabetes can benefit patients with CKD with and without diabetes, including those with moderate-to-advanced CKD.”

References

1. Chertow G, Vart P, Jongs N, et al. Effects of dapagliflozin in stage 4 chronic kidney disease. Journal of the American Society of Nephrology. July 2021. doi: https://doi.org/10.1681/ASN.2021020167

2. Dapagliflozin found effective and safe in adults with advanced kidney disease. News release. American Society of Nephrology; July 16, 2021. Accessed July 19, 2021. https://www.asn-online.org/about/press/releases/ASN_PR_20210716_JASN.Release.Cherto.pdf