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 (T2DM). The initial results from the trial, the first CV outcome study to enroll a large cohort of patients with diabetes and risk factors for Atherosclerotic Cardiovascular Disease (ASCVD) and a large number of patients with diabetes with known ASCVD, were presented at the American Diabetes Association’s (ADA’s) 79th Scientific Sessions.

DECLARE-TIMI is a multi-national, randomized, double-blind, placebo-controlled Phase III-B trial and is a superiority trial that enrolled over 17.000 patients across 882 sites from 33 countries. It was designed to test the hypothesis that, in patients with T2DM, long-term treatment with dapagliflozin will reduce one or both of the co-primary endpoints: 1) the incidence of CV death, myocardial infarction, or ischemic stroke or 2) the incidence of CV death or hospitalization for heart failure. The analysis evaluated data from 17,160 patients with T2DM and predominantly preserved renal function, irrespective of underlying ASCVD. Patients with diabetes are between six and 12 times more likely to develop end-stage renal disease (ESRD) and are twice as likely to develop chronic kidney disease (CKD).

In the first sub-analysis of renal data from Phase III, researchers found a 47% reduction in the relative risk of kidney function decline, ESRD, or renal death (excluding CV death) compared to placebo (1.5% vs. 2.6%; HR 0.53, 95% CI 0.43-0.66, P<0.0001). The risk of ESRD 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).

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.

The results were presented alongside other renal outcomes from DECLARE-TIMI 58, including positive results from an analysis that found dapagliflozin both reduced and prevented the worsening of UACR, across all UACR categories and regardless of a patient’s baseline UACR. An additional health economics analysis suggested that early use of dapagliflozin may reduce costs related to the treatment of CKD compared to placebo.

Source: press release ADA, June 10, 2019The data were simultaneously published in The_Lancet