The much awaited outcome of the DAPA-CKD (Dapagliflozin And Prevention of Adverse Outcomes in Chronic Kidney Disease ) trial was presented on 30 August 2020 at the ESC (European Society of Cardiology) Congress 2020 by Prof H. Heerspink.
Dapagliflozin is an SGLT2 ( Sodium-Glucose Co-transporter 2) inhibitor being used,so far, in the treatment of type 2 diabetes mellitus but there is now growing evidence in its renal and cardiac benefits in both non-diabetic and diabetic patients. The trial enrolled 4,304 patients, aged 18 years and over, from 386 centres in 21 countries. All patients had an eGFR ≥25 and ≤75 mL/min/1.73m2; urinary albumin to creatinine ratio between ≥200 mg/g and ≤5000 mg/g; and were on a stable, maximum tolerated dose of an ACE inhibitor or ARB (unless contraindicated) for at least four weeks.
Patients were randomly allocated to dapagliflozin 10 mg or placebo once daily in addition to standard of care (i.e. an ACE inhibitor or ARB). The average age of participants was 61.8 years and 66.9% were male. A total of 2,906 (67.5%) patients had type 2 diabetes. Patients with Type 1 DM, Polycystic kidney disease and ANCA vasculitis were not included in the trial.
The primary composite endpoint was worsening kidney function (defined as >50% sustained decline in estimated glomerular filtration rate [eGFR] or onset of end-stage kidney disease), or death due to kidney disease or cardiovascular disease.
The secondary endpoints were : 1) a composite endpoint of worsening kidney function (defined as >50% sustained decline in eGFR or onset of end-stage kidney disease), or death from kidney failure; 2) a composite endpoint of hospitalisation for heart failure or cardiovascular death; and 3) all-cause mortality.
Dapagliflozin reduces the risk of kidney failure, death from cardiovascular causes or heart failure hospitalisation and all-cause mortality in chronic kidney disease patients with or without type 2 diabetes.
The benefit of dapagliflozin on the primary endpoint was consistent in patients with and without type 2 diabetes. It also reduced all three secondary endpoints compared to placebo.
Diabetic ketoacidosis was not reported in any patient randomised to dapagliflozin and occurred in two patients in the placebo group. Neither diabetic ketoacidosis nor severe hypoglycaemia were observed in patients without type 2 diabetes.
There is no denying that the SGLT2 inhibitors have now made a formidable case for their use for renoprotection as well for cardioprotection in non-diabetic patients.