DECLARE-TIMI 58 phase III trial of Farxiga/Forxiga cut the progression of kidney disease in type 2 diabetes patients

The first sub-analysis of renal data from the Dapagliflozin Effect on Cardiovascular Events Thrombolysis In Myocardial Infarction (DECLARE-TIMI 58) phase III trial indicates that Farxiga/Forxiga (dapagliflozin), an oral sodium glucose cotransporter 2 (SGLT2) inhibitor from AstraZeneca, reduced the progression of kidney disease or renal death in patients with type 2 diabetes (T2D). 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).

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.

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, a key marker of kidney health, 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. The initial results from the trial, the first cardiovascular outcome study to enroll a large cohort of patients with diabetes 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.