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Kidney Week

Abstract: PO2629

Effect of Ertugliflozin on Initial eGFR Decline and Chronic Slope: Analyses from the VERTIS CV Trial

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Cherney, David, University of Toronto, Toronto, Ontario, Canada
  • Charbonnel, Bernard, Universite de Nantes, Nantes, Pays de la Loire, France
  • Cosentino, Francesco, Karolinska Institute & Karolinska University Hospital Solna, Stockholm, Sweden
  • Pratley, Richard E., AdventHealth Translational Research Institute, Orlando, Florida, United States
  • Dagogo-Jack, Samuel, University of Tennessee Health Science Center, Memphis, Tennessee, United States
  • Shih, Weichung J., Rutgers School of Public Health, Piscataway, New Jersey, United States
  • Mcguire, Darren K., University of Texas Southwestern Medical Center, Dallas, Texas, United States
  • Frederich, Robert, Pfizer Inc., Collegeville, Pennsylvania, United States
  • Maldonado, Mario, MSD Limited, London, United Kingdom
  • Liu, Jie, Merck & Co., Inc., Kenilworth, New Jersey, United States
  • Pong, Annpey, Merck & Co., Inc., Kenilworth, New Jersey, United States
  • Liu, Chih-Chin, Merck & Co., Inc., Kenilworth, New Jersey, United States
  • Cannon, Christopher P., Brigham and Women’s Hospital, Harvard Medical School, Boston, Boston, Massachusetts, United States
Background

SGLT2 inhibitors induce an initial reversible eGFR dip, based on natriuresis-induced reductions in glomerular pressure, with a return toward baseline over time in adults with T2DM. Preservation of the chronic eGFR slope by ≥0.75 mL/min/1.73m2/year with treatment predicts protection against CKD progression. We aimed to assess the impact of initial eGFR dip and chronic eGFR slope in the VERTIS CV trial (NCT01986881).

Methods

Patients with T2DM and ASCVD were randomized (1:1:1) to ertugliflozin 5 mg, 15 mg or placebo. Analyses assessed pooled ertugliflozin (n=5499) and placebo (n=2747). Patients were divided into 3 tertiles based on initial eGFR change at Week 6 (increase, small change or decrease). Changes in eGFR, hematocrit and uric acid were assessed at Weeks 6, 18, 52 and 156. Chronic eGFR slope/year by random coefficient models was also assessed.

Results

Glucosuria-associated effects (ie, uric acid) were larger in the eGFR increase tertile; natriuresis-associated effects (ie, hematocrit) were larger in the eGFR decrease tertile (Fig A, B). The ertugliflozin eGFR decrease tertile had the smallest decline in chronic eGFR slope (Fig C, D). Chronic slopes were similar across the placebo group tertiles and the rate of decline uniformly more rapid (Fig D). Mean placebo-adjusted effect of ertugliflozin on chronic eGFR slope (Weeks 6–156 [95% CI]) was 1.19 (0.95, 1.42) mL/min/1.73 m2/year (Fig E) and >0.75 mL/min/1.73 m2/year in all subgroups.

Conclusion

The initial eGFR dip may influence several clinical effects of ertugliflozin. Ertugliflozin has favorable effects on eGFR slope in patients with T2DM and ASCVD.

Funding

  • Commercial Support