Kidney Week

Abstract: PO2629

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

Session Information

• Late-Breaking Clinical Trials Posters
  October 22, 2020 | Location: On-Demand
  Abstract Time: 10:00 AM - 10:00 AM

Category: Diabetic Kidney Disease

• 602 Diabetic Kidney Disease: Clinical

Authors

• Cherney, David, University of Toronto, Toronto, Ontario, Canada

David Cherney,

• Charbonnel, Bernard, Universite de Nantes, Nantes, Pays de la Loire, France

Bernard Charbonnel,

• Cosentino, Francesco, Karolinska Institute & Karolinska University Hospital Solna, Stockholm, Sweden

Francesco Cosentino,

• Pratley, Richard E., AdventHealth Translational Research Institute, Orlando, Florida, United States

Richard E. Pratley,

• Dagogo-Jack, Samuel, University of Tennessee Health Science Center, Memphis, Tennessee, United States

Samuel Dagogo-Jack,

• Shih, Weichung J., Rutgers School of Public Health, Piscataway, New Jersey, United States

Weichung J. Shih,

• Mcguire, Darren K., University of Texas Southwestern Medical Center, Dallas, Texas, United States

Darren K. Mcguire,

• Frederich, Robert, Pfizer Inc., Collegeville, Pennsylvania, United States

Robert Frederich,

• Maldonado, Mario, MSD Limited, London, United Kingdom

Mario Maldonado,

• Liu, Jie, Merck & Co., Inc., Kenilworth, New Jersey, United States

Jie Liu,

• Pong, Annpey, Merck & Co., Inc., Kenilworth, New Jersey, United States

Annpey Pong,

• Liu, Chih-Chin, Merck & Co., Inc., Kenilworth, New Jersey, United States

Chih-Chin Liu,

• Cannon, Christopher P., Brigham and Women’s Hospital, Harvard Medical School, Boston, Boston, Massachusetts, United States

Christopher P. Cannon,

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 – Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA in collaboration with Pfizer Inc.