The first sub-analysis of renal data from the Dapagliflozin Effect on Cardiovascular Events Thrombolysis In Myocardial Infarction (DECLARE-TIMI 58) trial indicates that dapagliflozin, an oral sodium glucose cotransporter 2 (SGLT2) inhibitor, reduced the progression of kidney disease or renal death in patients with type 2 diabetes (T2D).
DECLARE-TIMI is a multi-national, randomized, double-blind, placebo-controlled Phase III-B trial and is a superiority trial designed to test the hypothesis that, in patients with T2D, long-term treatment with dapagliflozin will reduce one or both of the co-primary endpoints: 1) the incidence of cardiovascular death, myocardial infarction, or ischemic stroke or 2) the incidence of cardiovascular death or hospitalization for heart failure.
In the first sub-analysis of renal data from Phase III, researchers found a 47% reduction within the relative risk of kidney function decline, end-stage renal disease (ESRD), or renal death (excluding cardiovascular death) compared to placebo (1.5% vs. 2.6%; HR 0.53 [95% CI 0.43-0.66], p<0.0001). The risk of end-stage renal disease or renal death was lower in the dapagliflozin group than in the placebo group (11[0.1%] vs. 27 [0.3%]; HR 0.41 [95% CI 0.20-0.82]; p=0.012).
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The analysis evaluated data from 17,160 patients with T2D and predominantly preserved renal function, irrespective of underlying ASCVD. Patients with diabetes are between six and 12 times more likely to develop ESRD and are twice as likely to develop chronic kidney disease (CKD). While ESRD was a rare event in the trial, dapagliflozin significantly reduced the incidence when compared to the placebo (0.1% vs 0.3%, respectively). Acute kidney injury occurred in 1.5% and 2.0% in the dapagliflozin and placebo arms, respectively. Patients treated with the dapagliflozin experienced fewer clinically important renal outcomes, regardless of eGFR or urinary albumin-to-creatinine ratio (UACR) category, whether they had established ASCVD or multiple CV risk factors.
"Medications like dapagliflozin should also be considered as first line therapy in patients without established cardiovascular disease. The drugs have a high safety margin and should be used regularly by primary care physicians," said Itamar Raz, MD, professor of internal medicine at Hadassah Medical School at the Hebrew University of Jerusalem, head of the Israel National Council of Diabetes, and previous head of the Diabetes Unit at Hadassah University Hospital.