DAPA-CKD - dapagliflozin in reducing the risk of renal and cardiovascular events in chronic kidney disease (with and without type 2 diabetes)

Last edited 11/2022 and last reviewed 07/2023

DAPA-CKD trial investigated the effect of SGLT2 inhibitor dapagliflozin, compared to placebo, on the risk of renal and CV events in CKD patients, with or without T2DM

• a total of 4304 patients (>= 18 years of age) from 286 centers in 21 countries were included in the trial
• 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 already receiving a stable maximum tolerated dose of either an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) as background therapy
• average age was 61.8 years, 66.9% were male and 67.5% had T2DM
• patients were randomized to receive either dapagliflozin 10 mg one daily or matching placebo

The primary composite endpoint was worsening kidney function (defined as >=50% sustained decline in eGFR or onset of end-stage kidney disease), or renal or CV death

• the first secondary endpoint was a composite of worsening kidney function, or death from kidney failure
• second secondary endpoint was a composite of HF hospitalization or CV death. The third secondary endpoint was all-cause mortality.

The trial was stopped early due to overwhelming efficacy. This decision was made following a recommendation from an independent Data Monitoring Committee. The median follow-up was 2.4 years.

• dapagliflozin significantly reduced the risk of the primary endpoint with 39%, compared to placebo (HR 0.61, 95%CI 0.51-0.72, P=0.000000028). The benefit of dapagliflozin on the primary endpoint was consistent in patients with and without T2DM.
• compared to placebo, dapagliflozin reduced the risk on all three secondary endpoints: The composite of worsening kidney function or death from kidney failure (first secondary endpoint HR=0.56, 95%CI 0.45-0.68, P<0.0001), the composite of HF hospitalization or CV death (second secondary endpoint HR 0.71, 95%CI 0.55-0.92, P=0.0089, and all-cause mortality (third secondary endpoint HR 0.69, 95%CI 0.53-0.88, P=0.0035).
• proportion of patients who discontinued the drug or who experienced a serious adverse event in the placebo group (5.7% and 33.9%, respectively) was similar to dapagliflozin group (5.5% and 29.5%, respectively). Diabetic ketoacidosis occurred in two patients in the placebo group and was not reported in the dapagliflozin group. Neither diabetic ketoacidosis nor severe hypoglycemia were reported in patients without T2DM.

Dapagliflozin significantly reduced the risk of kidney failure, CV death or HF hospitalization, and all-cause mortality in patients with CKD, with and without T2DM, compared to placebo.

Reference:

• Heerspink HJL et al. Rationale and protocol of the Dapagliflozin And Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD) randomized controlled trial. Nephrol Dial Transplant. 2020 Feb 1;35(2):274-282. doi: 10.1093/ndt/gfz290.
• European Society of Cardiology (August 30th 2020). DAPA-CKD trial meets primary endpoint in patients with chronic kidney disease. DAPA-CKD trial presented in a Hot Line Session today at ESC Congress 2020.
• Hiddo JL et al. Dapagliflozin in Patients with Chronic Kidney Disease.N Engl J Med 2020; 383:1436-1446