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Abstract: FR-PO229

Early Dip in Estimated Glomerular Filtration Rate (eGFR) on the Efficacy of Ertugliflozin at Week 26

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Cherney, David, University of Toronto, Toronto, Ontario, Canada
  • Frederich, Robert, Pfizer Inc., Collegeville, Pennsylvania, United States
  • Liu, Jie, Merck & Co., Inc., Rahway, New Jersey, United States
  • Maldonado, Mario, MSD, London, United Kingdom
  • Pong, Annpey, Merck & Co., Inc., Rahway, New Jersey, United States
  • Gantz, Ira, Merck & Co., Inc., Rahway, New Jersey, United States
  • Terra, Steven G., Pfizer Inc., Andover, Massachusetts, United States
Background

In light of positive results from CREDENCE and previous cardiovascular outcome trials, sodium-glucose cotransporter 2 (SGLT2) inhibitors are frequently compared with renin-angiotensin-aldosterone system blockers, since some members of both drug classes reduce cardiorenal risk. The aim of this post-hoc analysis was to assess possible modulatory effects of the early eGFR dip observed with ertugliflozin on measures of treatment efficacy including changes in glycated hemoglobin (A1C), systolic blood pressure (SBP) and body weight (BW).

Methods

Data were pooled from three placebo-controlled studies of ertugliflozin 5 mg and 15 mg in adults with type 2 diabetes mellitus (N=1544). Patients were analyzed by quartiles (Q) of percent reduction in eGFR at Week 6 for changes from baseline in A1C, SBP and BW at Week 26. Pearson correlation was used to measure the strength of the linear relationship between the percent change in eGFR from baseline to Week 6 and changes in those endpoints.

Results

Patients in quartiles with the greatest eGFR decrease (Q1 and Q2) at Week 6 showed similar reductions in A1C at Week 26 compared with patients undergoing only small changes in eGFR (Q3) at Week 6 (Figure). Among patients with an increase in eGFR (Q4), those in the ertugliflozin 15 mg group, but not ertugliflozin 5 mg group, showed a greater reduction in A1C at Week 26 compared with other quartiles. Changes in SBP and BW were similar across all quartiles. A weak correlation (r=–0.138) between the change in eGFR at Week 6 and change in A1C at Week 26 was found in ertugliflozin 15 mg group.

Conclusion

Ertugliflozin causes an early decrease in eGFR but its degree has no meaningful impact on reductions in A1C, SBP or BW at Week 26. Ertugliflozin 15 mg may augment A1C reduction in patients with an eGFR rise during early treatment.

Change in A1C at Week 26 from baseline by quartiles of eGFR change at Week 6

Funding

  • Commercial Support – This study was sponsored by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and Pfizer Inc., New York, NY, USA.