Ertugliflozin and Slope of Chronic eGFR

Background and objectives: A reduction in the rate of eGFR decline, with preservation of ≥0.75 ml/min/1.73 m2/year, has been proposed as a surrogate for kidney disease progression. We report results from prespecified analyses assessing effects of ertugliflozin versus placebo on eGFR slope from the VERTIS CV trial (NCT01986881). Design, setting, participants, and measurements: Patients with type 2 diabetes mellitus and established atherosclerotic cardiovascular disease were randomized to placebo, ertugliflozin 5 mg, and ertugliflozin 15 mg (1:1:1). The analyses compared the effect of ertugliflozin (pooled doses, n=5499) versus placebo (n=2747) on eGFR slope per week and per year by random coefficient models. Study periods (weeks 0-6 and weeks 6-52) and total and chronic slopes (week 0 or week 6 to weeks 104, 156, 208, and 260) were modeled separately and by baseline kidney function status. Results: In the overall population, from weeks 0-6, the least square mean eGFR slopes (ml/min/1.73m2/week [95% CI]) were −0.07 (−0.16, 0.03) and −0.54 (−0.61, −0.48) for the placebo and ertugliflozin groups respectively; the difference was −0.47 (−0.59, −0.36). During weeks 6-52, least square mean eGFR slopes (ml/min/1.73 m2/year [95% CI]) were −0.12 (−0.70, 0.46) and 1.62 (1.21, 2.02) for the placebo and ertugliflozin groups respectively; the difference was 1.74 (1.03, 2.45) For weeks 6-156, least square mean eGFR slopes (ml/min/1.73 m2/year [95% CI]) were −1.51 (−1.70,−1.32) and −0.32 (−0.45,−0.19) for the placebo and ertugliflozin groups respectively; the difference was 1.19 (0.95,1.42). During weeks 0-156, the placebo-adjusted least square mean slope was 1.06 (0.85, 1.27). These findings were consistent by baseline kidney function status. Conclusion: Ertugliflozin has a favorable placebo-adjusted eGFR slope >0.75 ml/min/1.73 m2/year, documenting the kidney function preservation underlying the clinical benefits of ertugliflozin on kidney disease progression in patients with type 2 diabetes mellitus and atherosclerotic cardiovascular disease.