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

Abstract

<p> </p> <p><strong>Objective:</strong> 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).</p> <p><strong>Research Design and Methods:</strong> 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.</p> <p><strong>Results:</strong> The effects of dapagliflozin on the primary composite outcome was consistent across GLT classes and according to the number of GLTs (all interaction <em>P</em> >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).</p> <p><strong>Conclusion:</strong> Dapagliflozin reduced kidney and cardiovascular events in patients with type 2 diabetes and CKD across baseline GLT class or classes in combination.</p>

Results of the DAPA-CKD trial and their impact on clinical practice

“…Цікавим фактом є те, що у хворих без ЦД2 вплив дапагліфлозину на середній рівень HbA1 c не відрізнявся від плацебо [18] Крім того, позитивний ефект дапагліфлозину в підгрупі хворих із ЦД2 щодо серцевих і ниркових подій, а також профіль безпеки не залежали від того, які інші класи антигіперглікемічних препаратів отримували хворі та в якій кількості. Важливим результатом було вірогідне зменшення на 28 % ініціації терапії інсуліном у групі хворих, які отримували терапію дапагліфлозином, порівняно з плацебо [19].…”

Development and Validation of a Lifetime Risk Model for Kidney Failure and Treatment Benefit in Type 2 Diabetes

“…This was done by first fitting a linear mixed model on the effect of age (as time axis) on eGFR with a random intercept and random slope in the derivation cohort. Thereby individual eGFR slope was derived (21). The second step was to fit a linear model of eGFR slope (ml/min/1.73m2 per year) as a function of baseline age and baseline eGFR.…”