Even patients with stage 4 chronic kidney disease (CKD) can reap kidney, cardiovascular, and survival benefits from using the sodium-glucose co-transporter 2 inhibitor (SGLT2i) dapagliflozin, according to investigators.

In the Dapagliflozin And Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial, 624 of 4304 (14%) patients had stage 4 CKD (estimated glomerular filtration rate [eGFR] less than 30 mL/min/1.73 m2).

Compared with placebo, dapagliflozin treatment (10 mg/d) was associated with a significant 27% improvement in the primary composite endpoint of time to a 50% or more decline in eGFR, end-stage kidney disease, or kidney or cardiovascular death in patients with advanced CKD, Glenn M. Chertow, MD, MPH, of Stanford University in Palo Alto, California, and colleagues reported in the Journal of the American Society of Nephrology. Dapagliflozin significantly lowered the risks for the kidney and cardiovascular endpoints by 29% and 17%, respectively, and the risk for all-cause mortality by 32%.

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The dapagliflozin group had better preservation of kidney function than the placebo group, with eGFR decreasing by 2.15 vs 3.38 mL/min/1.73 m2 per year, respectively.

Patients treated with dapagliflozin or placebo had similar rates of serious adverse events (AEs) and AEs of interest, including major hypoglycemia, bone fractures, kidney-related events, and amputation, the investigators reported.

“This analysis shows that the effects of dapagliflozin in patients with stage 4 CKD are similar to effects in patients with mild to moderate CKD,” Dr Chertow stated in a press release from the American Society of Nephrology. “While patients with screening eGFR as low as 25 mL/min/1.73 m2 were enrolled, it is noteworthy that neither dapagliflozin nor placebo were discontinued when eGFR declined, even to below 15 mL/min/1.73 m2. Therefore, a drug initially developed for the treatment of diabetes can benefit patients with CKD with and without diabetes, including patients with moderate to advanced CKD.”

Disclosure: This research was supported by AstraZeneca. Please see the original reference for a full list of disclosures.


Chertow G, Vart P, Jongs N, et al. Effects of dapagliflozin in stage 4 chronic kidney disease. Published online on July 16, 2021. J Am Soc Nephrol. doi:10.1681/ASN.2021020167