303-OR: Effect of Dapagliflozin on Risk for Fast Decline in EGFR: Analyses from the DECLARE-TIMI 58 Trial

Abstract

SGLT2 inhibitors may lead to short term decrease in eGFR, with later stabilization and long-term reduction in the risk for end stage kidney disease. Fast decline (FD) in eGFR can be defined as a reduction of ≥3 ml/min/1.73m2/year and is associated with poor long-term renal prognosis. In this post-hoc analysis we studied the effect of dapagliflozin (dapa) on the risk for FD in the DECLARE-TIMI 58 trial. In DECLARE-TIMI 58, 17,160 patients with T2D and established or increased risk for CVD, with mean baseline eGFR of 85.2 ml/min/1.73m2, were randomized to dapa vs. placebo and followed for a median of 4.2 years. The risk for FD was compared between treatment arms. In the time frame of 0.5 years (after stabilization) to 4 years, the proportion of patients with FD was reduced with dapa vs. placebo (26.8% vs. 37.1% respectively, p<0.0001). This observation was persistent in all subgroups assessed (Table). The mean (SD) reduction in eGFR per year was 6.3 (3.7) vs. 0.0 (2.5) ml/min/1.73m2/year in the FD (N=4,788) vs. non-FD (N=10,224) patients. The proportion of patients with FD during the entire study period (i.e., 0-4 years) was reduced with dapa vs. placebo as well (33.6% vs. 37.0% respectively, p<0.0001). Dapagliflozin reduced the risk for FD in eGFR in a broad population of patients with T2D and either established or increased risk for CVD, but relatively preserved renal function, irrespective of patients’ baseline characteristics.