The Effect of Dapagliflozin on Albuminuria in DECLARE-TIMI 58
Methods: DECLARE-TIMI 58 randomized 17,160 patients with type-2 diabetes, Creatinine Clearance>60 ml/min, and either atherosclerotic cardiovascular disease (CVD); (40.6%) or risk-factors for CVD (59.4%) to dapagliflozin or placebo. Urinary albumin-creatinine ratio (UACR) was tested at baseline, 6-months, 12-months and yearly thereafter. Change in UACR over time was measured as a continuous and categorical variable (≤15; >15 to<30; ≥30-≤300; >300 mg/g), by treatment arm. Composite cardiorenal outcome was ≥40% sustained-decline in eGFR to <60 mL/min/1.73m², end-stage kidney disease, cardiovascular- or renal-death; specific renal outcome included all except cardiovascular-death.
Results: Baseline UACR was available for 16,843 (98.15%) participants; 9,067 (53.83%) with ≤15 mg/g; 2,577 (15.30%) with <15->30 mg/g; 4,030 (23.93%) with 30-300 mg/g; and 1,169 (6.94%) with >300 mg/g. Measured as continuous variable, UACR improved from baseline to 4.0 years with dapagliflozin, compared to placebo, across all UACR and eGFR categories (all p<0.0001). Sustained-confirmed ≥1 category improvement in UACR was more common in dapagliflozin vs. placebo [HR=1.45 (95%CI 1.35-1.56 p<0.0001)]. Cardiorenal outcome was reduced with dapagliflozin for subgroups of UACR ≥30 mg/g (p<0.0125, Pint=0.033); renal-specific outcome was reduced for all UACR subgroups (p<0.05, Pint=0.480).
Conclusion: In DECLARE-TIMI 58, dapagliflozin demonstrated a favourable effect on UACR and renal specific outcome across baseline UACR categories, including patients with normal albumin excretion. The results suggest a role for SGLT2i also in the primary prevention of diabetic kidney disease.