TY - JOUR
T1 - Effects of ertugliflozin on kidney composite outcomes, renal function and albuminuria in patients with type 2 diabetes mellitus
T2 - an analysis from the randomised VERTIS CV trial
AU - on behalf of the VERTIS CV Investigators
AU - Cherney, David Z.I.
AU - Charbonnel, Bernard
AU - Cosentino, Francesco
AU - Dagogo-Jack, Samuel
AU - McGuire, Darren K.
AU - Pratley, Richard
AU - Shih, Weichung J.
AU - Frederich, Robert
AU - Maldonado, Mario
AU - Pong, Annpey
AU - Cannon, Christopher P.
N1 - Funding Information:
Funding for this research was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., (Kenilworth, NJ, USA) in collaboration with Pfizer Inc. (New York, NY, USA). The authors would like to thank the participants, their families and all investigators involved in the VERTIS CV study; the list of investigators can be found with the primary publication [12]. Some of the results from these analyses were presented at the 56th annual meeting of the EASD. The authors would like to acknowledge J. L. and I. Gantz, both of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co Inc., (Kenilworth, NJ, USA), for their discussions with the authors and review of the manuscript and C-C. Liu of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co Inc., (Kenilworth, NJ, USA) for statistical support and review of the manuscript.
Funding Information:
This study was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., (Kenilworth, NJ, USA) in collaboration with Pfizer Inc. The sponsor was involved in the study design, collection, analysis and interpretation of data, as well as data checking of information provided in the manuscript.
Funding Information:
Funding for this research was provided by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., (Kenilworth, NJ, USA) in collaboration with Pfizer Inc. (New York, NY, USA). The authors would like to thank the participants, their families and all investigators involved in the VERTIS CV study; the list of investigators can be found with the primary publication []. Some of the results from these analyses were presented at the 56th annual meeting of the EASD. The authors would like to acknowledge J. L. and I. Gantz, both of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co Inc., (Kenilworth, NJ, USA), for their discussions with the authors and review of the manuscript and C-C. Liu of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co Inc., (Kenilworth, NJ, USA) for statistical support and review of the manuscript. Medical writing and/or editorial assistance was provided by M. Hammad and I. Norton, both of Scion (London, UK). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., (Kenilworth, NJ, USA) and Pfizer Inc. (New York, NY, USA). Critical reviewing of an early draft was provided by S. G. Terra of Pfizer Inc.
Funding Information:
DZIC has received consulting fees or speaking honorarium, 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. BC has received fees for the following activities: advisory boards for AstraZeneca, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. (Kenilworth, NJ, USA), Novo Nordisk, Sanofi and Servier; and speaker bureau for AstraZeneca, Eli Lilly, Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc. (Kenilworth, NJ, USA), Novo Nordisk, Sanofi and Takeda. FC has received fees from Abbott, AstraZeneca, Bayer, Bristol-Myers Squibb, Merck Sharp & Dohme, Novo Nordisk and Pfizer, as well as research grants from the Swedish Research Council, Swedish Heart & Lung Foundation and the King Gustav V and Queen Victoria Foundation. SD-J 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. DKM has had leadership roles in clinical trials for AstraZeneca, Boehringer Ingelheim, CSL Behring, Eisai, Esperion, GlaxoSmithKline, Janssen, Lexicon, Merck & Co., Inc., Novo Nordisk and Sanofi USA, and has received consultancy fees from AstraZeneca, Boehringer Ingelheim, Lilly USA, Merck & Co., Inc., Pfizer, Novo Nordisk, Metavant, Afimmune and Sanofi. RP has received the following fees (directed to his institution): speaker fees from Novo Nordisk; consulting fees from Merck & Co., Inc., 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. WJS has received fees for membership of the ertugliflozin advisory board of Merck & Co., Inc. (Kenilworth, NJ, USA). RF is an employee and shareholder of Pfizer Inc. MM is an employee of MSD UK and may own stock and/or stock options in Merck & Co., Inc. (Kenilworth, NJ, USA). AP is an employee 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). CPC reports grants and personal fees from Pfizer Inc., grants, personal fees from Merck & Co., Inc., during the conduct of the study. CPC also 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 Therapeutics, Ascendia, Corvidia, HLS Therapeutics, Innovent, Kowa, Sanofi, Eli Lilly, and Rhoshan, outside the submitted work.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/6
Y1 - 2021/6
N2 - Aims/hypothesis: In previous work, we reported the HR for the risk (95% CI) of the secondary kidney composite endpoint (time to first event of doubling of serum creatinine from baseline, renal dialysis/transplant or renal death) with ertugliflozin compared with placebo as 0.81 (0.63, 1.04). The effect of ertugliflozin on exploratory kidney-related outcomes was evaluated using data from the eValuation of ERTugliflozin effIcacy and Safety CardioVascular outcomes (VERTIS CV) trial (NCT01986881). Methods: Individuals with type 2 diabetes mellitus and established atherosclerotic CVD were randomised to receive ertugliflozin 5 mg or 15 mg (observations from both doses were pooled), or matching placebo, added on to existing treatment. The kidney composite outcome in VERTIS CV (reported previously) was time to first event of doubling of serum creatinine from baseline, renal dialysis/transplant or renal death. The pre-specified exploratory composite outcome replaced doubling of serum creatinine with sustained 40% decrease from baseline in eGFR. In addition, the impact of ertugliflozin on urinary albumin/creatinine ratio (UACR) and eGFR over time was assessed. Results: A total of 8246 individuals were randomised and followed for a mean of 3.5 years. The exploratory kidney composite outcome of sustained 40% reduction from baseline in eGFR, chronic kidney dialysis/transplant or renal death occurred at a lower event rate (events per 1000 person-years) in the ertugliflozin group than with the placebo group (6.0 vs 9.0); the HR (95% CI) was 0.66 (0.50, 0.88). At 60 months, in the ertugliflozin group, placebo-corrected changes from baseline (95% CIs) in UACR and eGFR were −16.2% (−23.9, −7.6) and 2.6 ml min−1 [1.73 m]−2 (1.5, 3.6), respectively. Ertugliflozin was associated with a consistent decrease in UACR and attenuation of eGFR decline across subgroups, with a suggested larger effect observed in the macroalbuminuria and Kidney Disease: Improving Global Outcomes in Chronic Kidney Disease (KDIGO CKD) high/very high-risk subgroups. Conclusions/interpretation: Among individuals with type 2 diabetes and atherosclerotic CVD, ertugliflozin reduced the risk for the pre-specified exploratory composite renal endpoint and was associated with preservation of eGFR and reduced UACR. Trial registration: ClinicalTrials.gov NCT01986881 Graphical abstract: [Figure not available: see fulltext.]
AB - Aims/hypothesis: In previous work, we reported the HR for the risk (95% CI) of the secondary kidney composite endpoint (time to first event of doubling of serum creatinine from baseline, renal dialysis/transplant or renal death) with ertugliflozin compared with placebo as 0.81 (0.63, 1.04). The effect of ertugliflozin on exploratory kidney-related outcomes was evaluated using data from the eValuation of ERTugliflozin effIcacy and Safety CardioVascular outcomes (VERTIS CV) trial (NCT01986881). Methods: Individuals with type 2 diabetes mellitus and established atherosclerotic CVD were randomised to receive ertugliflozin 5 mg or 15 mg (observations from both doses were pooled), or matching placebo, added on to existing treatment. The kidney composite outcome in VERTIS CV (reported previously) was time to first event of doubling of serum creatinine from baseline, renal dialysis/transplant or renal death. The pre-specified exploratory composite outcome replaced doubling of serum creatinine with sustained 40% decrease from baseline in eGFR. In addition, the impact of ertugliflozin on urinary albumin/creatinine ratio (UACR) and eGFR over time was assessed. Results: A total of 8246 individuals were randomised and followed for a mean of 3.5 years. The exploratory kidney composite outcome of sustained 40% reduction from baseline in eGFR, chronic kidney dialysis/transplant or renal death occurred at a lower event rate (events per 1000 person-years) in the ertugliflozin group than with the placebo group (6.0 vs 9.0); the HR (95% CI) was 0.66 (0.50, 0.88). At 60 months, in the ertugliflozin group, placebo-corrected changes from baseline (95% CIs) in UACR and eGFR were −16.2% (−23.9, −7.6) and 2.6 ml min−1 [1.73 m]−2 (1.5, 3.6), respectively. Ertugliflozin was associated with a consistent decrease in UACR and attenuation of eGFR decline across subgroups, with a suggested larger effect observed in the macroalbuminuria and Kidney Disease: Improving Global Outcomes in Chronic Kidney Disease (KDIGO CKD) high/very high-risk subgroups. Conclusions/interpretation: Among individuals with type 2 diabetes and atherosclerotic CVD, ertugliflozin reduced the risk for the pre-specified exploratory composite renal endpoint and was associated with preservation of eGFR and reduced UACR. Trial registration: ClinicalTrials.gov NCT01986881 Graphical abstract: [Figure not available: see fulltext.]
KW - Cardiovascular disease
KW - Diabetic nephropathies
KW - Ertugliflozin
KW - Type 2 diabetes mellitus
UR - http://www.scopus.com/inward/record.url?scp=85102173835&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85102173835&partnerID=8YFLogxK
U2 - 10.1007/s00125-021-05407-5
DO - 10.1007/s00125-021-05407-5
M3 - Article
C2 - 33665685
AN - SCOPUS:85102173835
SN - 0012-186X
VL - 64
SP - 1256
EP - 1267
JO - Diabetologia
JF - Diabetologia
IS - 6
ER -