CKD: dapagliflozin offers benefits regardless of diabetes status

  • Wheeler DC & al.
  • Lancet Diabetes Endocrinol
  • 1 Jan 2021

  • curated by Sarfaroj Khan
  • UK Clinical Digest
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Takeaway

  • Dapagliflozin lowers the risks of major adverse kidney and cardiovascular (CV) events and all-cause mortality in patients with chronic kidney disease (CKD), regardless of type 2 diabetes (T2D) status.
  • These benefits also extend to patients with a broad range of underlying causes of CKD other than diabetic nephropathy (DN), including those with primary glomerulonephritides and ischaemic or hypertensive kidney disease.

Why this matters

  • Dapagliflozin may provide substantial cardiorenal benefit to a broad range of patients with impaired kidney function and proteinuria, including patients with non-diabetic CKD.

Study design

  • In DAPA-CKD trial, 4304 patients with an estimated glomerular filtration rate (eGFR) of 25-75 mL/min/1.73m2 and a urinary albumin-to-creatinine ratio of 200-5000 mg/g were randomly assigned (1:1) to receive dapagliflozin or placebo in addition to standard of care.
  • This prespecified analysis of the DAPA-CKD trial investigated whether the presence or absence of T2D at baseline and the underlying aetiology of kidney disease modified the effects of dapagliflozin.
  • Primary composite outcome: sustained ≥50% eGFR decline, end-stage kidney disease (ESKD) and renal or CV death.
  • Funding: AstraZeneca.

Key results

  • Overall, 2906 (68%) patients had T2D, of whom 396 (14%) had CKD attributed to causes other than DN.
  • Dapagliflozin reduced the risk of the primary composite outcome in patients with T2D (HR, 0.64; 95% CI, 0.52-0.79) and in those without T2D (HR, 0.50; 95% CI, 0.35-0.72; Pinteraction=.24).
  • Similar results were seen for the secondary outcomes in patients with T2D vs those without:
    • sustained ≥50% eGFR decline, ESKD and renal death (HR, 0.57; 95% CI, 0.45-0.73 vs HR, 0.51; 95% CI, 0.34-0.75; Pinteraction=.57);
    • CV death or hospitalisation for HF (HR, 0.70; 95% CI, 0.53-0.92 vs HR, 0.79; 95% CI, 0.40-1.55; Pinteraction=.78); and
    • all-cause mortality (HR, 0.74; 95% CI, 0.56-0.98 vs HR, 0.52; 95% CI, 0.29-0.93; Pinteraction=.25).
  • The effect of dapagliflozin on the primary outcome was consistent in patients with DN (HR, 0.63; 95% CI, 0.51-0.78), glomerulonephritides (HR, 0.43; 95% CI, 0.26-0.71), ischaemic or hypertensive CKD (HR, 0.75; 95% CI, 0.44-1.26) and CKD of other or unknown causes (HR, 0.58; 95% CI, 0·29-1·19; Pinteraction=.53), with similar consistency seen across the secondary outcomes.

Limitations

  • T2D diagnosis was based on investigator-reported diagnosis or glycated haemoglobin values and not on more conventional tests.