Background and objectives: A reduction in the rate of eGFR decline, with preservation of ≥0.75 ml/min per 1.73 m2 per 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 eValuation of ERTugliflozin effIcacy and Safety CardioVascular outcomes (VERTIS CV) trial (NCT01986881).
Design, setting, participants, & 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 status.
Results: In the overall population, for weeks 0-6, the least squares mean eGFR slopes (ml/min per 1.73 m2 per week [95% confidence interval (95% CI)]) were -0.07 (-0.16 to 0.03) and -0.54 (-0.61 to -0.48) for the placebo and ertugliflozin groups, respectively; the difference was -0.47 (-0.59 to -0.36). During weeks 6-52, least squares mean eGFR slopes (ml/min per 1.73 m2 per year [95% CI]) were -0.12 (-0.70 to 0.46) and 1.62 (1.21 to 2.02) for the placebo and ertugliflozin groups, respectively; the difference was 1.74 (1.03 to 2.45). For weeks 6-156, least squares mean eGFR slopes (ml/min per 1.73 m2 per year [95% CI]) were -1.51 (-1.70 to -1.32) and -0.32 (-0.45 to -0.19) for the placebo and ertugliflozin groups, respectively; the difference was 1.19 (0.95 to 1.42). During weeks 0-156, the placebo-adjusted difference in least squares mean slope was 1.06 (0.85 to 1.27). These findings were consistent by baseline kidney status.
Conclusions: Ertugliflozin has a favorable placebo-adjusted eGFR slope >0.75 ml/min per 1.73 m2 per 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.
Clinical trial registry name and registration number: US National Library of Medicine, ClinicalTrials.gov NCT01986881. Date of trial registration: November 13, 2013.
Keywords: clinical trial; diabetic nephropathy; glomerular filtration rate; renal function decline; renal protection; sodium-glucose cotransporter 2 inhibitor; type 2 diabetes mellitus.
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