The Effect of Dapagliflozin on Albuminuria in DECLARE-TIMI 5
Sodium–glucose cotransporter 2 inhibitors (SGLT2i) improve albuminuria in patients with high cardiorenal risk. Authors report albuminuria change in the Dapagliflozin Effect on Cardiovascular Events (DECLARE-TIMI 58) cardiovascular outcome trial, which included populations with lower cardiorenal risk.

DECLARE-TIMI 58 randomized 17,160 patients with type 2 diabetes, creatinine clearance more than 60 mL/min, and either atherosclerotic cardiovascular disease (CVD; 40.6%) or risk-factors for CVD (59.4%) to dapagliflozin or placebo. Urinary albumin-to-creatinine ratio (UACR) was tested at baseline, 6 months, 12 months, and yearly thereafter. The change in UACR over time was measured as a continuous and categorical variable (less than 15, 15 to 30, 30 to 300, and more than 300 mg/g) by treatment arm. The composite cardiorenal outcome was a more than 40% sustained decline in the estimated glomerular filtration rate (eGFR) to less than 60 mL/min/1.73 m2, end-stage kidney disease, and cardiovascular or renal death; specific renal outcome included all except cardiovascular death.

-- Baseline UACR was available for 16,843 (98.15%) participants: 9,067 (53.83%) with less than 15 mg/g, 2,577 (15.30%) with 15 to 30 mg/g, 4,030 (23.93%) with 30–300 mg/g, and 1,169 (6.94%) with more than 300 mg/g.

-- Measured as a continuous variable, UACR improved from baseline to 4.0 years with dapagliflozin, compared with placebo, across all UACR and eGFR categories.

-- Sustained confirmed more than 1 category improvement in UACR was more common in dapagliflozin versus placebo.

-- Cardiorenal outcome was reduced with dapagliflozin for subgroups of UACR more than 30 mg/g, and the renal-specific outcome was reduced for all UACR subgroups.

Conclusively, in DECLARE-TIMI 58, dapagliflozin demonstrated a favorable 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.