Dapagliflozin Slows Rate of Kidney Function Decline, Regardless of Diabetes Status

Hiddo Heerspink, PhD, PharmD

A prespecified analysis of the DAPA-CKD trial is providing further insight into the association of dapagliflozin use with a reduction in the rate of kidney function decline in patients with chronic kidney disease (CKD), regardless of whether they have diabetes.

Presented at the American Society of Nephrology’s Kidney Week 2021, results of the study demonstrate dapagliflozin significantly reduced the rate of kidney function decline while also providing insight into the potential differences in effect sizes seen in patients with and without diabetes.

“The key conclusion is that dapagliflozin is an effective treatment to slow progressive kidney function loss in patients with CKD with and without type 2 diabetes,” said lead author Hiddo Lambers Heerspink, PhD, PharmD, of the University Medical Center Groningen, in a statement. “Therefore, in addition to reducing the risk of heart failure or mortality, as previously shown in the DAPA-CKD trial, dapagliflozin also slows the progression of kidney function decline.”

One of the most groundbreaking trials of the 21st century, results of DAPA-CKD have been a subject of discussion among cardiologists, endocrinologists, nephrologists, and others since the results were originally presented at the ESC Congress 2020. Since then, dapagliflozin has received approval for use in CKD patients with and without type 2 diabetes based on trial results and numerous prespecified analyses of DAPA-CKD have provided further insight into the effects of dapagliflozin use in these patients.

Presented by Heerspink at Kidney Week 2021, this prespecified analysis was designed to assess rate of change in eGFR slope using mixed effect models with different slopes from baseline to week 2, week 2 to end-of-treatment, and baseline to end-of-treatment. Of note, the baseline to week 2 period was considered acute change, week 2 to end-of-treatment was considered the chronic eGFR slope, and the baseline to end-of-treatment period, which assessed eGFR at a median of 2.3 years, was considered total eGFR slope.

Results of the analysis indicated dapagliflozin use slowed mean eGFR decline from baseline to end-of-treatment by 0.9 mL/min/1.73m2 (95% CI, 0.6-1.3) per year compared to placebo therapy. When assessing acute eGFR decline, results suggested dapagliflozin was associated with an acute eGFR decline of 2.6 mL/min/1.73m2 (95%CI, 2.2–3.1) and 2.0 mL/min/1.73m2 (95% CI, 1.4–2.7) in patients with and without type 2 diabetes, respectively, compared to placebo therapy. Following week 2, the mean rate of eGFR decline seen with dapagliflozin was greater among patients with type 2 diabetes (chronic eGFR slope mean difference: 2.3 mL/min/1.73m2 per year [95% CI, 1.9–2.6]) than in those without type 2 diabetes (1.3 mL/min/1.73m2 per year [95% CI, 0.7–1.8]; interaction P=.005).

For total slope in eGFR, results of the investigators’ analysis suggested the effects of dapagliflozin use, compared to placebo therapy, on total slope in patients with and without type 2 diabetes was 1.2 mL/min/1.73m2 per year (95% CI, 0.8–1.6) and 0.5 mL/min/1.73m2 per year (95%CI −0.1 to 1.0; interaction P=.04), respectively. Investigators also pointed out results of their analysis suggested the total eGFR slope was steeper among patients with higher baseline HbA1c and UACR and the apparent beneficial effects of dapagliflozin on eGFR slope was greater in those with higher baseline HbA1c and UACR.

This study, “The effect of dapagliflozin on rate of kidney function decline in patients with chronic kidney disease: a prespecified analysis from the DAPA-CKD,” was presented at ASN Kidney Week 2021.