TY - JOUR
T1 - Ertugliflozin and slope of chronic egfr prespecified analyses from the randomized vertis cv trial
AU - VERTIS-CV Investigators
AU - Cherney, David Z.I.
AU - Cosentino, Francesco
AU - Dagogo-Jack, Samuel
AU - McGuire, Darren K.
AU - Pratley, Richard
AU - Frederich, Robert
AU - Maldonado, Mario
AU - Liu, Chih Chin
AU - Liu, Jie
AU - Pong, Annpey
AU - Cannon, Christopher P.
N1 - Funding Information:
C.P. Cannon reports grants and personal fees from Pfizer Inc. and grants and personal fees from Merck & Co., Inc. during the conduct of the study. C.P. Cannon reports grants and personal fees from Amgen, Boehringer Ingelheim, Bristol Myers Squibb, and Janssen; grants from Daiichi Sankyo and Novo Nordisk; and personal fees from Aegerion, Alnylam, Amarin, Applied Clinical Therapeutics, Ascendia, Corvidia, Eli Lilly, HLS Therapeutics, Innovent, Kowa, Lexicon, Rhoshan, and Sanofi, outside the submitted work. D.Z.I. Cherney has received consulting fees or speaking honorarium, or both, from Abbvie, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim-Lilly, Bristol Myers Squibb, Janssen, JNJ, MAZE, Merck & Co., Inc., Mitsubishi-Tanabe, Novo Nordisk, Otsuka, Prometic, and Sanofi; has received operating funds from AstraZeneca, Boehringer Ingelheim-Lilly, Janssen, Merck & Co., Inc., Novo Nordisk, and Sanofi; and has served as a scientific advisor or member of AstraZeneca, Boehringer Ingelheim, Janssen, Merck, Novo Nordisk, and Sanofi. F. Cosentino has received fees from Abbott, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol Myers Squibb, Lilly, Merck Sharp & Dohme, Novo Nordisk, and Pfizer; research grants from the King Gustav V and Queen Victoria Foundation, the Swedish Heart & Lung Foundation, and the Swedish Research Council; and serves as Deputy Editor of the European Heart Journal and Consulting Editor of the Cardiovascular Research Journal. S. Dagogo-Jack has led clinical trials for AstraZeneca, Bayer, Boehringer Ingelheim, and Novo Nordisk, Inc.; has received fees from AstraZeneca, Bayer, Boehringer Ingelheim, Janssen, Merck & Co., Inc. and Sanofi; holds equity interests in Jana Care, Inc. and Aerami Therapeutics; and serves on editorial boards of the American Journal of the Medical Sciences, BMJ Diabetes Research & Care, and Frontiers in Endocrinology. R. Frederich is an employee and shareholder of Pfizer Inc. and may own shares/stock options in Pfizer Inc. and may own stock in Bristol Myers Squibb. M. Maldonado is an employee of MSD UK. He may own stock and/or stock options in Merck & Co., Inc., Ken-ilworth, NJ, USA. D.K. McGuire has had leadership roles in clinical trials for AstraZeneca, Boehringer Ingelheim, CSL Behring, Eisai, Esperion, GlaxoSmithKline, Janssen, Lexicon, Lilly USA, Merck & Co., Inc., Novo Nordisk, and Sanofi USA and has received consultancy fees from Afimmune, Applied Therapeutics, AstraZeneca, Boehringer Ingelheim, Lexicon, Lilly USA, Merck & Co., Inc., Meta-vant, Novo Nordisk, Metavant, Pfizer, and Sanofi. C-C. Liu, J. Liu, and A. Pong are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, and may own stock and/or stock options in Merck & Co., Inc., Kenilworth, NJ, USA. R. Pratley is an employee of AdventHealth Translational Research Institute; has received (directed to his institution) speaker fees from Novo Nordisk; speaker fees and consulting fees from Merck & Co., Inc.; and grants from Hanmi Pharmaceuticals Co., Jans-sen, Lexicon Pharmaceuticals, Metavention, Novo Nordisk, Poxel SA, and Sanofi. R. Pratley has received consulting fees from AstraZe-neca, Corcept Therapeutics Incorporated, Glytec LLC, Janssen, Mun-dipharma, Novo Nordisk, Pfizer, Sanofi, Scohia Pharma Inc., and Sun Pharmaceutical Industries. Except for services for Sanofi US Services Inc. on 2/12/2018 and 6/25/2018 (which were paid to R. Pratley personally), all payments are made directly to his employer.
Funding Information:
The authors would like to thank the patients, their families, and all investigators involved in the eValuation of ERTugliflozin effIcacy and Safety CardioVascular outcomes study. The authors would like to personally thank Ira Gantz, of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co Inc., Kenilworth, NJ, for technical assistance and advice. Medical writing and/or editorial assistance was provided by Dr. Moamen Hammad and Dr. Ian Norton, both of Scion, London, UK. This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, and Pfizer Inc., New York, NY.
Publisher Copyright:
© 2021 by the American Society of Nephrology.
PY - 2021/9
Y1 - 2021/9
N2 - 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 0–6andweeks6–52) 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 peryear[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.
AB - 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 0–6andweeks6–52) 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 peryear[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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85114668304&partnerID=8YFLogxK
U2 - 10.2215/CJN.01130121
DO - 10.2215/CJN.01130121
M3 - Article
C2 - 34497110
AN - SCOPUS:85114668304
SN - 1555-9041
VL - 16
SP - 1345
EP - 1354
JO - Clinical Journal of the American Society of Nephrology
JF - Clinical Journal of the American Society of Nephrology
IS - 9
ER -