Dapagliflozin Safety and Efficacy in Advanced CKD

Dapagliflozin is known to improve kidney outcomes in patients with chronic kidney disease (CKD), but it is unclear what effect late initiation of the drug has when eGFR is <25 mL/min/1.73m².

To improve understanding, Chi-Chih Hung, Yi-Wen Chiu, and Shang-Jyh Hwang studied the efficacy and safety of dapagliflozin in patients with CKD stages 4 and 5. They shared findings during the oral presentation, Efficacy and Safety of Dapagliflozin in Patients with CKD Stages 4-5 at ASN Kidney Week 2024.

The DAPA advKD trial (NCT05196347) was a randomized5p-, open-label trial that recruited 180 patients with eGFR 10-30 mL/min/1.73m² and eGFR decline ≥2.5 mL/min/1.73m²/year. These patients were randomized 2:1 to dapagliflozin (5-10 mg/d) plus integrated CKD care, or integrated CKD care only.

The primary study outcome was maintenance of eGFR decline ≥0.75 ml/min/1.73m²/year. The first secondary outcome was renal endpoint (a composite of renal replacement therapy, eGFR <5 mL/min/1.73m², renal or cardiovascular [CV] death, or a >50% eGFR decline). The second secondary outcome was renal and CV endpoint (a composite of renal outcome as defined above, acute kidney injury [AKI], and heart failure). Predefined safety outcomes were measured.

During a median period of 1.62 years, total eGFR slopes were -2.24 mL/min/1.73m²/year (-4.70 to -0.62 mL/min/1.73m²/year) for the dapagliflozin group and -3.67 mL/min/1.73m²/year (-7.16 to -1.25 mL/min/1.73m²/year) for the control group. The primary outcome of eGFR slope decline was 1.06 ml/min/1.73m²/year (0.10 to 0.32 ml/min/1.73m²/year; P=.019, linear mixed model).

The secondary renal outcome occurred in 24/120 (20%) patients in the dapagliflozin group, and in 21/60 (35%) in the control group (HR, 0.50 [0.28 to 0.89], P=.019). The secondary renal and CV outcome occurred in 25/120 (21%) patients in the dapagliflozin group and 21/60 (35.0%) in the control group (HR, 0.52 [0.29 to 0.93], P=.028). The control group experienced higher rates of heart failure and AKI but had a higher incidence of eGFR decline.

The researchers concluded, “Among patients with eGFR 10-30 mL/min/1.73m², the risks of eGFR decline and composite renal outcomes were lower with dapagliflozin than with control group.”

Source: Hung C-C, Chiu Y-W, Hwang S-J. Efficacy and safety of dapagliflozin in patients with CKD stages 4-5. SA-OR96. Abstract of an oral presentation at the American Society of Nephrology Kidney Week 2024; October 26, 2024; San Diego, California. Funding was provided by AstraZeneca.