Dapagliflozin and prevention of kidney disease among patients with type 2 diabetes– post hoc analyses from the DECLARE-TIMI 58 trial

Jamie P Dwyer,Darren K Mcguire,Martin Fredriksson,Marc S Sabatine,Itamar Raz,Anna Maria Langkilde,Hiddo J.L Heerspink,Sabina A Murphy,Aliza Rozenberg,Ilan Yanuv,Ofri Mosenzon,Erica L Goodrich,Deepak L Bhatt,Meir Schechter,Stephen D Wiviott,Lawrence A Leiter ,Thomas A Zelniker ,John Wilding ,Ingrid Gause‐Nilsson ,Peter Johansson ,Avivit Cahn

doi:10.2337/figshare.20365530

Abstract

Objective: In patients with moderate-severe albuminuric kidney disease, sodium-glucose co-transporter-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. Methods: In the 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 sustained decline ≥40% in estimated glomerular filtration rate (eGFR) to<60mL/min/1.73m², end-stage kidney disease, and kidney-related death. Other outcomes included incidence of categorical eGFR decline of different thresholds and chronic (6-months 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 (HR 0.54, 95%CI 0.38-0.77). Risks for categorical eGFR reductions (≥57% [in those with baseline eGFR≥60ml/min/1.73m2], ≥50%, ≥40%, and ≥30%) were lower with dapagliflozin (HR= 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). Conclusion: 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.

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