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- Title
The Effect of Dapagliflozin on Albuminuria in DECLARE-TIMI 58.
- Authors
Mosenzon, Ofri; Wiviott, Stephen D.; Heerspink, Hiddo J.L.; Dwyer, Jamie P.; Cahn, Avivit; Goodrich, Erica L.; Rozenberg, Aliza; Schechter, Meir; Yanuv, Ilan; Murphy, Sabina A.; Zelniker, Thomas A.; Gause-Nilsson, Ingrid A.M.; Langkilde, Anna Maria; Fredriksson, Martin; Johansson, Peter A.; Bhatt, Deepak L.; Leiter, Lawrence A.; McGuire, Darren K.; Wilding, John P.H.; Sabatine, Marc S.
- Abstract
<bold>Objective: </bold>Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve albuminuria in patients with high cardiorenal risk. We report albuminuria change in the Dapagliflozin Effect on Cardiovascular Events (DECLARE-TIMI 58) cardiovascular outcome trial, which included populations with lower cardiorenal risk.<bold>Research Design and Methods: </bold>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-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 (≤15, >15 to <30, ≥30 to ≤300, and >300 mg/g) by treatment arm. The composite cardiorenal outcome was a ≥40% sustained decline in the estimated glomerular filtration rate (eGFR) to <60 mL/min/1.73 m2, end-stage kidney disease, and cardiovascular or renal death; specific renal outcome included all except cardiovascular death.<bold>Results: </bold>Baseline UACR was available for 16,843 (98.15%) participants: 9,067 (53.83%) with ≤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 >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 (all P < 0.0001). Sustained confirmed ≥1 category improvement in UACR was more common in dapagliflozin versus placebo (hazard ratio 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, Pinteraction = 0.033), and the renal-specific outcome was reduced for all UACR subgroups (P < 0.05, Pinteraction = 0.480).<bold>Conclusions: </bold>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.
- Subjects
SODIUM-glucose cotransporter 2 inhibitors; DIABETIC nephropathies; DAPAGLIFLOZIN; CHRONIC kidney failure; ALBUMINURIA; BENZENE; GLOMERULAR filtration rate; RESEARCH; GLYCOSIDES; MEDICAL cooperation; TYPE 2 diabetes; COMPARATIVE studies; RANDOMIZED controlled trials; STATISTICAL sampling; DISEASE complications
- Publication
Diabetes Care, 2021, Vol 44, Issue 8, p1805
- ISSN
0149-5992
- Publication type
journal article
- DOI
10.2337/dc21-0076