Dapagliflozin improves kidney function in patients with diabetes patients with CKD: Lancet
Delhi: Dapagliflozin compared with placebo significantly improves the rate of decline in kidney function in patients with chronic kidney disease (CKD), show results from a prespecified analysis from the DAPA-CKD trial. The study, published in the journal The Lancet Diabetes and Endocrinology found that the mean difference in estimated glomerular filtration rate (eGFR) slope between patients treated with dapagliflozin versus placebo was higher in patients with type 2 diabetes, higher UACR, and higher HbA1c.
DAPA-CKD is a randomized controlled trial that enrolled participants aged 18 years or older, with or without type 2 diabetes with a urinary albumin-to-creatinine ratio (UACR) of 200–5000 mg/g, and an eGFR of 25–75 mL/min per 1·73m2. They were randomly assigned in the ratio of 1:1 to receive oral dapagliflozin 10 mg once daily or a placebo added to standard care. In this pre-specified analysis, Prof Hiddo J L Heerspink, University of Groningen, University Medical Center Groningen, Groningen, Netherlands, and colleagues analyzed eGFR slope using mixed-effect models with different slopes from baseline to week 2 (acute eGFR decline), week 2 to end of treatment (chronic eGFR slope), and baseline to end of treatment (total eGFR slope).
4304 participants were recruited between Feb 2, 2017, and April 3, 2020, of whom 2152 (50%) were assigned to dapagliflozin and 2152 (50%) were assigned to placebo. At baseline, the mean age was 62 years, 1425 (33·1%) participants were women, 2906 (67·5%) participants had type 2 diabetes. The median on-treatment follow-up was 2·3 years.
Key findings include:
- From baseline to the end of treatment, dapagliflozin compared with placebo slowed eGFR decline by 0·95 mL/min per 1·73 m2 per year in the overall cohort.
- Between baseline and week 2, dapagliflozin compared with placebo resulted in an acute eGFR decline of 2·61 mL/min per 1·73 m2 in patients with type 2 diabetes and 2·01 mL/min per 1·73 m2 in those without type 2 diabetes.
- Between week 2 and end of treatment, dapagliflozin compared with placebo reduced the mean rate of eGFR decline by a greater amount in patients with type 2 diabetes (mean difference in chronic eGFR slope 2·26 mL/min per 1·73 m2 per year) than in those without type 2 diabetes (1·29 mL/min per 1·73 m2 per year).
- Between baseline and end of treatment, the effect of dapagliflozin compared with placebo on the decline of total eGFR slope in patients with type 2 diabetes was 1·18 mL/min per 1·73 m2 per year (and without type 2 diabetes was 0·46 mL/min per 1·73 m2 per year.
- The total eGFR slope was steeper in patients with higher baseline HbA1c and UACR; the effect of dapagliflozin on eGFR slope was also more pronounced in patients with higher baseline HbA1c and UACR.
"Dapagliflozin significantly slowed long-term eGFR decline in patients with chronic kidney disease compared with placebo," concluded the authors. "The mean difference in eGFR slope between patients treated with dapagliflozin versus placebo was greater in patients with type 2 diabetes, higher HbA1c, and higher UACR."
Reference:
The study titled, "Effect of dapagliflozin on the rate of decline in kidney function in patients with chronic kidney disease with and without type 2 diabetes: a prespecified analysis from the DAPA-CKD trial," is published in the
