Efficacy of Dapagliflozin by Baseline Diabetes Medications: A Prespecified Analysis From the DAPA-CKD Study

Abstract

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 4,304 adults (including 2,906 with type 2 diabetes) with a baseline estimated glomerular filtration rate (eGFR) 25–75 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio of 200–5,000 mg/g to dapagliflozin 10 mg or placebo once daily (NCT03036150). The primary end point was a composite of ≥50% eGFR decline, end-stage kidney disease, and kidney or cardiovascular cause of death. Secondary end points included a kidney composite end point (primary composite end point without cardiovascular death), a cardiovascular composite end point (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 were consistent across GLT classes and according to the number of GLTs (all interaction P > 0.08). Similarly, we found consistent benefit of dapagliflozin compared with placebo on the secondary end points regardless of background GLT class or number of GLTs. The same applied to the rate of decline in the eGFR rate and safety end points. Dapagliflozin reduced the initiation of insulin therapy during follow-up compared with placebo (hazard ratio 0.72; 95% CI 0.54–0.96; P = 0.025). CONCLUSIONS Dapagliflozin reduced kidney and cardiovascular events in patients with type 2 diabetes and CKD across baseline GLT class or classes in combination.

Tumor Necrosis Factor-α G-308A Polymorphism and Sporadic IgA Nephropathy: A Meta-Analysis Using a Genetic Model-Free Approach

“…The armamentarium of the single renin-angiotensin system (RAS) blockade is further expanded with the use of sparsentan, a dual endothelin angiotensin receptor antagonist (DEARA) whose reno-protective effects were evaluated in PROTECT trial versus irbesartan [42]. Furthermore, sodium-glucose cotransporter-2 inhibitors (SGLT2i) constitute a novel therapeutic approach with promising results, although the precise mechanism of action has not been deciphered yet [43,44].…”