Dapagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, has demonstrated efficacy in slowing the decline of kidney function in patients with advanced chronic kidney disease (CKD) stages 4 and 5. The Dapagliflozin and Renal Surrogate Outcomes in Advanced CKD (DAPA advKD) trial revealed that dapagliflozin reduces the risk of estimated glomerular filtration rate (eGFR) decline and negative renal outcomes in individuals with eGFR rates between 10 and 30 mL/min/1.73m². These findings, presented at ASN Kidney Week 2024, highlight the potential of dapagliflozin to benefit patients with severely reduced kidney function.
DAPA advKD Trial Results
The open-label DAPA advKD trial enrolled 180 patients with stages 4 and 5 CKD, randomizing them in a 2:1 ratio to either dapagliflozin combined with integrated CKD care or integrated CKD care alone. Patients included had eGFR levels between 10-30 mL/min/1.73m² and eGFR declines of at least 2.5 mL/min/1.73m²/yr. The primary endpoint was the preservation of eGFR decline of at least 0.75 ml/min/1.73m²/yr. Secondary outcomes included a composite of renal replacement therapy, eGFR less than 5 mL/min/1.73m², renal or cardiovascular death, or at least a 50% decline in eGFR, as well as a composite of renal outcomes, acute kidney injury, and heart failure.
After a median follow-up of 1.62 years, the dapagliflozin group exhibited an average eGFR rate of -2.24 mL/min/1.73 m² compared to -3.67 mL/min/1.73 m² in the control group. This indicates a significant slowing of kidney function decline with dapagliflozin treatment. Furthermore, the dapagliflozin group experienced lower rates of kidney events and cardiovascular outcomes, including acute kidney injury and heart failure.
Impact on Type 1 Diabetes
Dapagliflozin has also shown promise in improving kidney function and glycemic control in youth and adolescents with type 1 diabetes. Data from the ATTEMPT study, presented at the American Diabetes Association (ADA) Scientific Sessions, revealed that low-dose dapagliflozin attenuated direct measures of GFR and was associated with a significant decline in HbA1c of 0.48% (P = .001) over 16 weeks in 98 participants with T1D. While there was a single case of mild diabetic ketoacidosis (DKA) in the dapagliflozin group, the overall benefits suggest a potential role in optimizing diabetes management and reducing kidney disease progression in this population.
Expert Commentary
"Our study focused on patients with advanced chronic kidney disease to test whether dapagliflozin can still benefit those with severely reduced kidney function. We found that this medication helped slow the decline in kidney function and reduced the need for dialysis or other advanced treatments," said Yi-Wen Chiu, MD, of Kaohsiung Medical University Hospital, in Taiwan. "Our next steps are to continue studying its long-term safety and effectiveness in this group."
"This study paves the way for us to evaluate treatments that can reduce kidney disease progression for those with type 1 diabetes," added Farid Mahmud, MD, of the University of Toronto. "These findings also give us meaningful insights as we look how we optimize diabetes management in youth and young adults during a challenging period associated with kidney disease progression and above-target A1c."
