2021 06 23 DECLARE-TIMI 58 albuminuria -supplamentary FINAL proofed_cx01.pdf (347.29 kB)
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The Effect of Dapagliflozin on Albuminuria in DECLARE-TIMI 58

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posted on 23.07.2021, 00:00 authored by Ofri Mosenzon, Stephen D Wiviott, Hiddo H J Heerspink, Jamie P Dwyer, Avivit Cahn, Erica L Goodrich, Aliza Rozenberg, Meir Schechter, Ilan Yanuv, Sabina A Murphy, Thomas A Zelniker, Ingrid A M Gause-Nilsson, Anna Maria Langkilde, Martin Fredriksson, Peter A Johansson, Deepak L Bhatt, Lawrence A Leiter, Darren K McGuire, John P H Wilding, Marc S Sabatine, Itamar Raz
Objective: Sodium glucose co-transporter 2 inhibitors (SGLT2i) improve albuminuria in patients with high cardiorenal risk. We report albuminuria change in the DECLARE-TIMI 58 cardiovascular outcome trial, which included populations with lower cardiorenal risk.

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.


The DECLARE–TIMI 58 trial was initially funded by AstraZeneca and Bristol-Myers Squibb; by the time of publication AstraZeneca was the sole funder.