TY - JOUR
T1 - Initial eGFR Changes with Ertugliflozin and Associations with Clinical Parameters
T2 - Analyses from the VERTIS CV Trial
AU - the VERTIS CV Investigators
AU - Cherney, David Z.I.
AU - Cosentino, Francesco
AU - Dagogo-Jack, Samuel
AU - McGuire, Darren K.
AU - Pratley, Richard E.
AU - Frederich, Robert
AU - Maldonado, Mario
AU - Liu, Chih Chin
AU - Pong, Annpey
AU - Cannon, Christopher P.
N1 - Funding Information:
D.Z.I. Cherney has received consulting fees or speaking honoraria, or both, from Bristol Myers Squibb, Novo Nordisk, Mitsubishis-Tanabe, MAZE, Janssen, Bayer, Boehringer Ingelheim–Eli Lilly, AstraZeneca, Merck & Co., Inc., Prometic, and Sanofi, and has received operating funds from Janssen, Boehringer Ingelheim–Eli Lilly, Sanofi, AstraZeneca, and Merck & Co., Inc. F. Cosentino has received fees from Abbott; AstraZeneca; Bayer; Boehringer Ingelheim; Bristol Myers Squibb; Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc, Rahway, NJ, USA; Novo Nordisk; and Pfizer, as well as research grants from Swedish Research Council, Swedish Heart & Lung Foundation, and the King Gustav V and Queen Victoria Foundation. S. Dagogo-Jack has led clinical trials for AstraZeneca, Novo Nordisk, Inc., and Boehringer Ingelheim, has received fees from AstraZeneca, Boehringer Ingelheim, Janssen, Merck & Co. Inc., and Sanofi, and holds equity interests in Jana care, Inc. and Aerami Therapeutics. D.K. McGuire has received honoraria for leadership roles in clinical trials for AstraZeneca, Boehringer Ingelheim, Eisai, Esperion, GlaxoSmithKline, Janssen, Lexicon, Merck & Co., Inc., Novo Nordisk, CSL Behring, and Sanofi USA, and has received consultancy fees from AstraZeneca, Boehringer Ingelheim, Lilly USA, Merck & Co., Inc., Bayer, Pfizer, Novo Nordisk, Metavant, Afimmune, Lexicon, Applied Therapeutics, and Sanofi USA. R.E. Pratley has received the following (directed to his institution): speaker fees from Novo Nordisk; consulting fees from Merck, Novo Nordisk, Pfizer, Sanofi, Scohia Pharma Inc., and Sun Pharmaceutical Industries; and grants from Lexicon Pharmaceuticals, Hanmi Pharmaceuticals Co., Novo Nordisk, Poxel SA, and Sanofi. R. Frederich is an employee and shareholder of Pfizer Inc. M. Maldonado is an employee of MSD UK, who may own stock and/or stock options in Merck & Co., Inc., Rahway, NJ, USA. C.-C. Liu and A. Pong are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, who may own stock and/or stock options in the Company. C.P. Cannon reports research grants and consulting fees from Pfizer Inc. and Merck & Co., Inc.; and research grants and consulting fees from Amgen, Boehringer Ingelheim, Bristol-Myers Squibb, and Janssen, research grants from Better Therapeutics, Daiichi Sankyo, and Novo Nordisk, and consulting fees from Aegerion/Amryt, Alnylam, Amarin, Applied Therapeutics, Ascendia, Lexicon, Sanofi, Eli Lilly, and Rhoshan, and reports serving on the Data and Safety Monitoring Boards for the Veteran’s Administration, Applied Therapeutics and NovoNordisk, outside the submitted work.
Funding Information:
Funding for this research was provided by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA, in collaboration with Pfizer Inc., New York, NY, USA. The authors would like to thank the patients, their families, and all investigators involved in the VERTIS CV trial. Medical writing and/or editorial assistance was provided by Moamen Hammad, PhD, and Ian Norton, PhD, both of Scion, London, UK. This assistance was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and Pfizer Inc., New York, NY, USA. The authors would like to acknowledge Jie Liu, MD, PhD, of Merck & Co Inc., Rahway, NJ, USA, for his review of an early draft of the manuscript, Ira Gantz, MD, of Merck & Co Inc., Rahway, NJ, USA, for his input and discussions with the authors, Ingrid Adamson of Merck & Co Inc., Rahway, NJ, USA, for her support with the safety analyses, and Philip Jones of Pfizer Inc., New York, NY, USA, for his support with the safety analyses. Some of these results have been presented at the American Society of Nephrology Kidney Week 2020 Reimagined congress. The sponsor was involved in the trial design and collection, analysis, and interpretation of data, as well as data checking of information provided in the manuscript. However, ultimate responsibility for opinions, conclusions, and data interpretation lies with the authors.
Publisher Copyright:
© 2022 The Author(s).
PY - 2022
Y1 - 2022
N2 - Introduction: Using data from the ertugliflozin cardiovascular outcomes trial in patients with type 2 diabetes mellitus (VERTIS CV; NCT01986881), associations between the initial estimated glomerular filtration rate (eGFR) "dip"with eGFR slope, glucosuria/natriuresis-related measures, and safety were investigated. Methods: Patients were categorized into tertiles based on change in eGFR at week 6: >+1.00 mL/min/1.73 m2 (tertile 1), >-5.99 and ≤+1.00 (tertile 2), and ≤-6.00 (tertile 3). eGFR slope after week 6 and week 18 was assessed by tertile. Glucosuria/natriuresis-related measures were also determined. Adverse events (AEs) were analyzed in the acute (baseline-week 6) and chronic periods (week 6-30 days after last dose of trial medication). Results: In the ertugliflozin group, chronic eGFR slopes (95% CI, mL/min/1.73 m2/year; weeks 6-156) were-0.76 (-1.03,-0.50),-0.29 (-0.51,-0.07), and-0.05 (-0.26, 0.17) in tertiles 1, 2, and 3, respectively (p value <0.001), and approximately-1.5 mL/min/1.73 m2/year across tertiles in the placebo group (p value = 0.79). At week 18, least squares mean (LSM) changes from baseline in glycated hemoglobin (%) were-0.77,-0.71, and-0.67 in tertiles 1, 2, and 3, respectively, in the ertugliflozin group; a similar tertile-associated trend was observed for uric acid. At week 18, LSM changes from baseline in hematocrit (%) were 2.07, 2.33, and 2.55 in tertiles 1, 2, and 3, respectively, in the ertugliflozin group; similar tertile-associated trends were observed for blood pressure. All pinteraction values were <0.0001 for glucosuria-and natriuresis-related measures. Kidney-related AEs were reported more frequently in tertiles 3 and 2 in the chronic period for both placebo-and ertugliflozin-treated groups. In both periods and in all tertiles, incidences of AEs did not differ between placebo-and ertugliflozin-treated groups. Conclusion: With ertugliflozin, the tertile with the largest initial dip in eGFR had a slower rate of chronic eGFR decline. Initial eGFR changes were associated with changes in both glucosuria-and natriuresis-related measures.
AB - Introduction: Using data from the ertugliflozin cardiovascular outcomes trial in patients with type 2 diabetes mellitus (VERTIS CV; NCT01986881), associations between the initial estimated glomerular filtration rate (eGFR) "dip"with eGFR slope, glucosuria/natriuresis-related measures, and safety were investigated. Methods: Patients were categorized into tertiles based on change in eGFR at week 6: >+1.00 mL/min/1.73 m2 (tertile 1), >-5.99 and ≤+1.00 (tertile 2), and ≤-6.00 (tertile 3). eGFR slope after week 6 and week 18 was assessed by tertile. Glucosuria/natriuresis-related measures were also determined. Adverse events (AEs) were analyzed in the acute (baseline-week 6) and chronic periods (week 6-30 days after last dose of trial medication). Results: In the ertugliflozin group, chronic eGFR slopes (95% CI, mL/min/1.73 m2/year; weeks 6-156) were-0.76 (-1.03,-0.50),-0.29 (-0.51,-0.07), and-0.05 (-0.26, 0.17) in tertiles 1, 2, and 3, respectively (p value <0.001), and approximately-1.5 mL/min/1.73 m2/year across tertiles in the placebo group (p value = 0.79). At week 18, least squares mean (LSM) changes from baseline in glycated hemoglobin (%) were-0.77,-0.71, and-0.67 in tertiles 1, 2, and 3, respectively, in the ertugliflozin group; a similar tertile-associated trend was observed for uric acid. At week 18, LSM changes from baseline in hematocrit (%) were 2.07, 2.33, and 2.55 in tertiles 1, 2, and 3, respectively, in the ertugliflozin group; similar tertile-associated trends were observed for blood pressure. All pinteraction values were <0.0001 for glucosuria-and natriuresis-related measures. Kidney-related AEs were reported more frequently in tertiles 3 and 2 in the chronic period for both placebo-and ertugliflozin-treated groups. In both periods and in all tertiles, incidences of AEs did not differ between placebo-and ertugliflozin-treated groups. Conclusion: With ertugliflozin, the tertile with the largest initial dip in eGFR had a slower rate of chronic eGFR decline. Initial eGFR changes were associated with changes in both glucosuria-and natriuresis-related measures.
KW - Clinical trial
KW - Diabetic nephropathy
KW - Glomerular filtration rate
KW - Kidney function decline
KW - Kidney protection
KW - Sodium-glucose cotransporter 2 inhibitor
KW - Type 2 diabetes mellitus
UR - http://www.scopus.com/inward/record.url?scp=85133129669&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85133129669&partnerID=8YFLogxK
U2 - 10.1159/000524889
DO - 10.1159/000524889
M3 - Article
C2 - 35691283
AN - SCOPUS:85133129669
SN - 0250-8095
JO - American Journal of Nephrology
JF - American Journal of Nephrology
ER -