DAPA-CKD: Dapagliflozin improves CKD survival ± diabetes

The DAPA-CKD trial found that the sodium glucose co-transporter 2 (SGLT2) inhibitor dapagliflozin reduced worsening kidney function or death from renal or cardiovascular disease by 39% [1]. DAPA-CKD assessed the effects of dapagliflozin on chronic kidney disease (CKD) in patients with and without type 2 diabetes mellitus (T2DM). The reductions of this primary endpoint were 36% and even 50% in patients with and without diabetes, respectively.

Previously, the CREDENCE study showed that the SGLT2 inhibitor canagliflozin was associated with a 30% risk reduction in renal decline and cardiovascular and renal death among patients with T2DM [2]. In the DAPA-CKD trial, a third of participants did not have diabetes. This raises the prospect of using dapagliflozin to prevent kidney failure in a new group of patients.

Prof. Hiddo Heerspink (University of Groningen, the Netherlands) presented the results of the randomised, double-blind, placebo-controlled DAPA-CKD trial, which enrolled 4,304 patients from 386 centres in 21 countries to assess the impact of dapagliflozin 10 mg versus placebo alongside standard of care (i.e. ACE inhibitor or ARB) [1]. Participants had a urinary albumin to creatinine ratio of ≥200 mg/g and an estimated glomerular filtration rate (eGFR) between 25-75 mL/min/1.73 m². Average age was 61.8 years, 66.9% were male, and 67.5% had T2DM. The primary endpoint was a composite of sustained decline in eGFR of ≥50%, end-stage renal disease, and renal or cardiovascular mortality.

During a median follow-up of 2.4 years, 197 primary events occurred with dapagliflozin compared with 312 events with placebo (HR 0.61; 95% CI 0.51-0.72; P<0.0001). The primary endpoint was 36% lower with dapagliflozin versus placebo (HR 0.64) in patients with T2DM and 50% lower in patients without diabetes (HR 0.50). In addition, dapagliflozin was associated with a significant reduction in in the 3 secondary endpoints compared with placebo, namely:

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    • a 31% reduction in risk of all-cause mortality (HR 0.69; P=0.0035);
    • a 29% reduction in hospitalisation for heart failure or cardiovascular death (HR 0.71; P=0.0089); and
    • a 44% reduction in worsening function or death from kidney failure (HR 0.56; P<0.0001).

In the placebo group, slightly more patients had serious adverse events than in the dapagliflozin group (33.9% vs 29.5%). The rate of patients that discontinued the drug due to an adverse event was similar (5.7% vs 5.5%). No patients in the dapagliflozin group and 2 patients in the placebo arm experienced diabetic ketoacidosis. Additionally, no severe hypoglycaemia or diabetic ketoacidosis were reported in patients without T2DM.

Results from DAPA-CKD affirm the role of SGLT2 inhibition in the prevention of renal decline and kidney failure. These results show that SGLT2 inhibitors have clearly moved beyond their initial use as glucose-lowering therapies in T2DM.

 

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   1. Heerspink H. Dapagliflozin in patients with chronic kidney disease: DAPA-CKD. Hot Line 2 Session, ESC Congress 2020, 30 Aug.
   2. Perkovic V, et al. N Engl J Med 2019; 380:2295-2306.

 



Posted on 5 November, 202025 March, 2024