Dapagliflozin Safe and Effective in Stage 4 Chronic Kidney Disease, DAPA-CKD Analysis Finds

Data from a prespecified analysis of the landmark DAPA-CKD trial suggests the effects of dapagliflozin in patients with advanced chronic kidney disease (CKD) were similar to those observed in patients with normal or moderately impaired kidney function.

A look at the effects of the SGLT2 inhibitor among the 624 patients with stage 4 CKD at baseline, results of the study indicate dapagliflozin use in these patients was not associated with an increased rate of side effects while still providing significant reductions in the incidence of the trial’s primary endpoint of declining kidney function or death.

"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," said Glenn Chertow, MD, MPH, Professor of Medicine at Stanford University School of Medicine, in a statement from the American Society of Nephrology. "While patients with screening eGFR as low as 25 mL/min/1.73m2 were enrolled, it is noteworthy that neither dapagliflozin nor placebo were discontinued when eGFR declined, even to below 15 mL/min/1.73m2.”

Dapagliflozin became the first SGLT2 inhibitor to receive approval for treatment of CKD in April 2021. Despite the historic approval and phase 3 data supporting use, an initial eGFR dip and other factors contribute to the risk-treatment paradox seen with the sluggish uptick in prescribing rates plaguing the class. The current study was a prespecified analysis designed to assess the efficacy and safety of dapagliflozin in patients with an eGFR less than 30 mL/min per 1.73m2 at baseline.

The original DAPA-CKD trial enrolled 4304 patients and compared dapagliflozin 10 mg daily against placebo therapy among patients with chronic kidney disease with or without diabetes. The trial’s primary endpoint was a composite of sustained decline in eGFR of 50% or more, end-stage kidney disease, or death from renal or cardiovascular causes. Over a median follow-up of 2.4 years,

For the prespecified secondary analysis, which assessed for the same composite outcome, investigators compared the effects among 293 patients who received dapagliflozin and 331 patients who received placebo. Upon analysis, results suggested dapagliflozin was associated with a 27% (HR, 0.73; 95% CI, 0.53-1.0) reduction in risk of the primary endpoint and 29% (HR, 0.71; 95% CI, 0.49-1.02), 17% (HR, 0.83; 95% CI, 0.45-1.53), and 32% (HR, 0.68; 95% CI, 0.39-1.21) reductions in the kidney, cardiovascular, and mortality endpoints, respectively, compared with those randomized to placebo.

Further analysis indicated the eGFR slope declined by 2.5 mL/min per 1.73m2 per year among those receiving dapagliflozin compared to 3.38 mL/min per 1.73m2 per year among those receiving placebo. Investigators also pointed out similar rates of serious adverse events and adverse events of interest occurred among patients receiving dapagliflozin or placebo.

“Among patients with stage 4 CKD and albuminuria, with and without type 2 diabetes, the effects of dapagliflozin on reducing the risks of major kidney and cardiovascular events and attenuating progressive loss of eGFR are consistent with those observed in the trial overall, with no evidence of increased risks. Dapagliflozin should be considered part of the therapeutic armamentarium for patients with stage 4 CKD and albuminuria,” wrote investigators.

This study, “Effects of Dapagliflozin in Stage 4 Chronic Kidney Disease,” was published in the Journal of the American Society of Nephrology.