Dapagliflozin shows efficacy in chronic kidney disease

Article written by Bruce Sylvester

Patients with chronic kidney disease have achieved improved outcomes with dapagliflozin treatment, researchers reported on October 8, 2020 in the NEJM/New England Journal of Medicine

“Among patients with chronic kidney disease, regardless of the presence or absence of diabetes, the risk of a composite of a sustained decline in the estimated GFR (glomerular filtration rate ) of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes was significantly lower with dapagliflozin than with placebo.”

As background, the authors noted that in prior trials sodium–glucose cotransporter 2 (SGLT2) inhibitors, like dapagliflozin, decreased glycated hemoglobin levels and shown positive effects on kidney and cardiovascular outcomes. “The CREDENCE (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) trial showed that long-term administration of canagliflozin [another SGLT2 inhibitor]  conferred renal and cardiovascular protection in patients with type 2 diabetes with chronic kidney disease.”

The researchers randomized assigned 4304 subjects with an estimated glomerular filtration rate (GFR) of 25 to 75 ml per minute per 1.73 m² of body-surface area and a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of 200 to 5000 to treatment with dapagliflozin (10 mg once daily) or placebo.

The primary outcome was a composite of sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes.

Due to the efficacy of dapagliflozin the trial ended early.

Over a median of 2.4 years, a primary outcome event occurred in 197 of 2152 subjects (9.2%) in the dapagliflozin group and 312 of 2152 (14.5%) in the placebo group (P<0.001).

Sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal causes was significantly higher among placebo subjects compared to dapagliflozin subjects (P<0.001). Composite of death from cardiovascular causes or hospitalization for heart failure was also significantly higher in the placebo group (P=0.009).

One hundred and one subjects (4.7%) in the dapagliflozin group and 146 subjects (6.8%) in the placebo group died, a significant difference (P=0.004).

“The effects of dapagliflozin were similar in participants with type 2 diabetes and in those without type 2 diabetes. The known safety profile of dapagliflozin was confirmed,” the authors reported.

“The present trial showed that persons with chronic kidney disease who received dapagliflozin had a significantly lower risk of a composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes than those who received placebo, independent of the presence or absence of type 2 diabetes. In addition, those who received dapagliflozin had a lower risk of death from cardiovascular causes or hospitalization for heart failure and had longer survival,” the authors concluded.