In a phase III trial, patients with CKD who received dapagliflozin in addition to standard care showed a significant reduction in all-cause mortality compared with those who received placebo plus standard care.
Commenting on dapagliflozin's approval for the new indication, Professor David Wheeler, Professor of Kidney Medicine at University College London, said: 'This decision is a significant milestone for people living with chronic kidney disease. It provides healthcare professionals with an effective new option that can slow progression of disease and possibly delay the need for dialysis.
As a clinician, I am thrilled to see advances like this, which have the potential to transform the experiences of many of the people living with this condition.'
Renal outcomes trial
The double-blind DAPA-CKD trial randomised 4304 patients with CKD stages 2–4 and albuminuria, with and without type II diabetes, to receive dapagliflozin 10mg or placebo once daily. Participants also received standard of care, which included an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker.
The primary composite endpoint was worsening of renal function or risk of death (defined as a composite of an eGFR decline ≥50%, onset of end-stage renal disease or death from cardiovascular or renal cause).
Over a median of 2.4 years, dapagliflozin, in addition to standard of care, significantly reduced the relative risk of the composite primary endpoint by 39% compared with placebo (hazard ratio 0.61; 95% CI 0.51–0.72, p<0.001).
Dapagliflozin also significantly reduced the relative risk of the secondary outcome of death from any cause by 31% versus placebo (hazard ratio 0.69; 95% CI 0.53 to 0.88, p=0.004) .
Absolute risk reductions for these two endpoints were 5.3% and 2.1%, respectively.
The safety profile of dapagliflozin was consistent with that previously reported. Serious adverse events occurred in 29.5% of patients treated with dapagliflozin and 33.9% of those who received placebo; 5.5% and 5.7% of patients discontinued treatment due to an adverse event in the dapagliflozin and placebo groups, respectively.
There were no reports of diabetic ketoacidosis with dapagliflozin and hypoglycaemic episodes did not occur in patients without diabetes.