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- Title
Dapagliflozin and Prevention of Kidney Disease Among Patients With Type 2 Diabetes: Post Hoc Analyses From the DECLARE-TIMI 58 Trial.
- Authors
Mosenzon, Ofri; Raz, Itamar; Wiviott, Stephen D.; Schechter, Meir; Goodrich, Erica L.; Yanuv, Ilan; Rozenberg, Aliza; Murphy, Sabina A.; Zelniker, Thomas A.; Langkilde, Anna Maria; Gause-Nilsson, Ingrid A.M.; Fredriksson, Martin; Johansson, Peter A.; Wilding, John P.H.; McGuire, Darren K.; Bhatt, Deepak L.; Leiter, Lawrence A.; Cahn, Avivit; Dwyer, Jamie P.; Heerspink, Hiddo J.L.
- Abstract
<bold>Objective: </bold>In patients with moderate to severe albuminuric kidney disease, sodium-glucose cotransporter 2 inhibitors reduce the risk of kidney disease progression. These post hoc analyses assess the effects of dapagliflozin on kidney function decline in patients with type 2 diabetes (T2D), focusing on populations with low kidney risk.<bold>Research Design and Methods: </bold>In the Dapagliflozin Effect on Cardiovascular Events-Thrombolysis in Myocardial Infarction 58 (DECLARE-TIMI 58) trial, patients with T2D at high cardiovascular risk were randomly assigned to dapagliflozin versus placebo. Outcomes were analyzed by treatment arms, overall, and by Kidney Disease: Improving Global Outcomes (KDIGO) risk categories. The prespecified kidney-specific composite outcome was a sustained decline ≥40% in the estimated glomerular filtration rate (eGFR) to <60 mL/min/1.73 m2, end-stage kidney disease, and kidney-related death. Other outcomes included incidence of categorical eGFR decline of different thresholds and chronic (6 month to 4 year) or total (baseline to 4 year) eGFR slopes.<bold>Results: </bold>Most participants were in the low-moderate KDIGO risk categories (n = 15,201 [90.3%]). The hazard for the kidney-specific composite outcome was lower with dapagliflozin across all KDIGO risk categories (P-interaction = 0.97), including those at low risk (hazard ratio [HR] 0.54, 95% CI 0.38-0.77). Risks for categorical eGFR reductions (≥57% [in those with baseline eGFR ≥60 mL/min/1.73 m2], ≥50%, ≥40%, and ≥30%) were lower with dapagliflozin (HRs 0.52, 0.57, 0.55, and 0.70, respectively; P < 0.05). Slopes of eGFR decline favored dapagliflozin across KDIGO risk categories, including the low KDIGO risk (between-arm differences of 0.87 [chronic] and 0.55 [total] mL/min/1.73 m2/year; P < 0.0001).<bold>Conclusions: </bold>Dapagliflozin mitigated kidney function decline in patients with T2D at high cardiovascular risk, including those with low KDIGO risk, suggesting a role of dapagliflozin in the early prevention of diabetic kidney disease.
- Subjects
MYOCARDIAL infarction complications; GLOMERULAR filtration rate; BENZENE; RESEARCH; SODIUM; RESEARCH methodology; GLYCOSIDES; EVALUATION research; TYPE 2 diabetes; COMPARATIVE studies; RANDOMIZED controlled trials; GLUCOSE; DIABETIC nephropathies; DISEASE complications
- Publication
Diabetes Care, 2022, Vol 45, Issue 10, p2350
- ISSN
0149-5992
- Publication type
Article
- DOI
10.2337/dc22-0382