Efficacy of dapagliflozin by baseline diabetes medications: A prespecified analysis from the DAPA-CKD study

Objective: To determine whether the benefits of dapagliflozin in patients with type 2 diabetes and chronic kidney disease (CKD) in the Dapagliflozin And Prevention of Adverse Outcomes in CKD trial (DAPA-CKD) varied by background glucose-lowering therapy (GLT).

Research Design and Methods: We randomized 4304 adults (including 2906 with type 2 diabetes) with baseline eGFR 25–75 mL/min/1.73m2 and urinary albumin:creatinine ratio 200–5000 mg/g to dapagliflozin 10mg or placebo once daily (NCT03036150). The primary endpoint was a composite of ≥50% eGFR decline, end-stage kidney disease, and kidney or cardiovascular death. Secondary endpoints included a kidney composite endpoint (primary composite endpoint without cardiovascular death), a cardiovascular composite endpoint (hospitalized heart failure or cardiovascular death), and all-cause mortality. In this prespecified analysis, we investigated the effects of dapagliflozin on these and other outcomes according to baseline GLT class or number of GLTs.

Results: The effects of dapagliflozin on the primary composite outcome was consistent across GLT classes and according to the number of GLTs (all interaction P >0.08). Similarly, we found consistent benefit of dapagliflozin compared to placebo on the secondary endpoints regardless of background GLT class or number of GLTs. The same applied to the rate of decline in estimated glomerular filtration rate and safety endpoints. Dapagliflozin reduced the initiation of insulin therapy during follow-up compared to placebo (HR 0.72 (0.54–0.96), P=0.025).

Conclusion: Dapagliflozin reduced kidney and cardiovascular events in patients with type 2 diabetes and CKD across baseline GLT class or classes in combination.