TY - JOUR
T1 - Dapagliflozin and Prevention of Kidney Disease Among Patients With Type 2 Diabetes
T2 - Post Hoc Analyses From the DECLARE-TIMI 58 Trial
AU - Mosenzon, Ofri
AU - Raz, Itamar
AU - Wiviott, Stephen D.
AU - Schechter, Meir
AU - Goodrich, Erica L.
AU - Yanuv, Ilan
AU - Rozenberg, Aliza
AU - Murphy, Sabina A.
AU - Zelniker, Thomas A.
AU - Langkilde, Anna Maria
AU - Gause-Nilsson, Ingrid A.M.
AU - Fredriksson, Martin
AU - Johansson, Peter A.
AU - Wilding, John P.H.
AU - McGuire, Darren K.
AU - Bhatt, Deepak L.
AU - Leiter, Lawrence A.
AU - Cahn, Avivit
AU - Dwyer, Jamie P.
AU - Heerspink, Hiddo J.L.
AU - Sabatine, Marc S.
N1 - Publisher Copyright:
© 2022 by the American Diabetes Association.
PY - 2022/10
Y1 - 2022/10
N2 - OBJECTIVE 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. RESEARCH DESIGN AND METHODS 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. RESULTS 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, re-spectively; 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). CONCLUSIONS Dapagliflozin mitigated kidney function decline in patients with T2D at high cardiovascular risk, including those with low KDIGO risk, suggesting a role of dapagli-flozin in the early prevention of diabetic kidney disease.
AB - OBJECTIVE 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. RESEARCH DESIGN AND METHODS 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. RESULTS 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, re-spectively; 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). CONCLUSIONS Dapagliflozin mitigated kidney function decline in patients with T2D at high cardiovascular risk, including those with low KDIGO risk, suggesting a role of dapagli-flozin in the early prevention of diabetic kidney disease.
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U2 - 10.2337/dc22-0382
DO - 10.2337/dc22-0382
M3 - Article
C2 - 35997319
AN - SCOPUS:85139375303
SN - 0149-5992
VL - 45
SP - 2350
EP - 2359
JO - Diabetes care
JF - Diabetes care
IS - 10
ER -