Abstract
INTRODUCTION: Using data from the VERTIS CV trial (NCT01986881), the impact of ertugliflozin in patients with nonalbuminuric diabetic kidney disease (DKD-non-Alb) was assessed. METHODS: Patients with type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD) were randomized to ertugliflozin or placebo. Subgroups were defined by estimated glomerular filtration rate (eGFR) (ml/min per 1.73 m(2)) and urinary albumin-to-creatinine ratios (UACRs) (mg/g): DKD-Non-Alb (eGFR < 60 + UACR < 30, n = 867); Alb DKD stage 3 (DKD stage 3 Alb, eGFR < 60 + UACR ≥ 30, n = 891); Alb DKD stages 1 + 2 (DKD stages 1-2 Alb, eGFR ≥ 60 + UACR ≥ 30, n = 2356); and no DKD (non-DKD, eGFR ≥ 60 + UACR < 30, n = 3916). eGFR slopes, eGFR and UACR over time, time to first event of a prespecified exploratory kidney composite outcome, albuminuria progression, and hospitalization for heart failure (HHF) were assessed. RESULTS: Total eGFR slopes (ml/min per 1.73 m(2) per year; weeks 0-260) with placebo were -0.23, -1.27, -2.29, and -1.19 for the DKD-Non-Alb, DKD stage 3 Alb, DKD stages 1 to 2 Alb, and non-DKD subgroups, respectively (P < 0.0001). Similar trends were found with ertugliflozin but with reduced rates of decline. Ertugliflozin treatment resulted in a significant reduction in the risk for albuminuria progression across subgroups, with Alb subgroups having the largest relative risk reduction (P(interaction) = 0.04). The hazard ratios (HRs) for ertugliflozin revealing reduction in the risk of the exploratory kidney composite outcome versus placebo was consistent across subgroups (P(interaction) = 0.34). Alb and the DKD-non-Alb subgroups had a larger relative risk reduction in the HHF outcome compared with other subgroups (P(interaction) = 0.046). CONCLUSION: Among the subgroups, participants with DKD-non-Alb had the slowest rate of eGFR decline. Ertugliflozin treatment resulted in reductions in albuminuria and slower decline in eGFR across subgroups. The effect of ertugliflozin on the HHF outcome was larger in those with more advanced kidney disease.