Efficacy and Safety of Dapagliflozin by Baseline Glycemic Status: A Prespecified Analysis From the DAPA-CKD Trial

Abstract

Objective: The Dapagliflozin and Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD) study demonstrated risk reduction for kidney and cardiovascular outcomes with dapagliflozin versus placebo in participants with chronic kidney disease (CKD) with and without diabetes. We compared outcomes according to baseline glycemic status.

Research design and methods: We enrolled participants with CKD, estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73 m2, and urinary albumin-to-creatinine ratio 200-5,000 mg/g. The primary composite end point was sustained eGFR decline ≥50%, end-stage kidney disease, or kidney or cardiovascular death.

Results: Of 4,304 participants, 738 had normoglycemia, 660 had prediabetes, and 2,906 had type 2 diabetes. The effect of dapagliflozin on the primary outcome was consistent (P for interaction = 0.19) in normoglycemia (hazard ratio [HR] 0.62 [95% CI 0.39, 1.01]), prediabetes (HR 0.37 [0.21, 0.66]), and type 2 diabetes (HR 0.64 [0.52, 0.79]). We found no evidence for effect modification on any outcome. Adverse events were similar, with no major hypoglycemia or ketoacidosis in participants with normoglycemia or prediabetes.

Conclusions: Dapagliflozin safely reduced kidney and cardiovascular events independent of baseline glycemic status.

Trial registration: ClinicalTrials.gov NCT03036150.

© 2021 by the American Diabetes Association.

Figures

Figure 1

A: Forest plot of the primary composite outcome of ≥50% eGFR decline, end-stage kidney disease (ESKD), or death from cardiovascular (CV) or kidney causes with dapagliflozin compared with placebo by glycemic status at baseline. B: The treatment effect of dapagliflozin compared with placebo as a function of baseline HbA1c (continuous) for the primary outcome. The solid black line represents the HR of the treatment effect. The gray shaded area represents the 95% CI around the treatment effects. The dotted horizontal line represents a HR of 1 (i.e., no difference between randomized groups).