PMID- 34620621 OWN - NLM STAT- MEDLINE DCOM- 20211012 LR - 20211023 IS - 2052-4897 (Electronic) IS - 2052-4897 (Linking) VI - 9 IP - 1 DP - 2021 Oct TI - Glycemic efficacy and safety of the SGLT2 inhibitor ertugliflozin in patients with type 2 diabetes and stage 3 chronic kidney disease: an analysis from the VERTIS CV randomized trial. LID - 10.1136/bmjdrc-2021-002484 [doi] LID - e002484 AB - INTRODUCTION: Here we report the glycemic efficacy and safety of ertugliflozin in patients in the VERTIS CV cardiovascular outcome trial with chronic kidney disease (CKD) stage 3. RESEARCH DESIGN AND METHODS: Prespecified and post-hoc analyses were performed in patients with an estimated glomerular filtration rate (eGFR) 30-<60 mL/min/1.73 m(2) at screening. The primary endpoint was glycemic efficacy at week 18. Longer term glycemic efficacy and changes in body weight, systolic blood pressure (SBP), and eGFR were also evaluated. RESULTS: Among 8246 patients in VERTIS CV, 1776 patients had CKD stage 3; 1319 patients had CKD stage 3A (eGFR 45-<60 mL/min/1.73 m(2)); 457 patients had CKD stage 3B (eGFR 30-<45 mL/min/1.73 m(2)). Week 18 least squares (LS)-mean (95% CI) placebo-adjusted changes from baseline in glycated hemoglobin (HbA1c) for 5 mg and 15 mg ertugliflozin were -0.27% (-0.37% to -0.17%) and -0.28% (-0.38% to -0.17%), respectively, for CKD stage 3 overall and -0.27% (-0.38% to -0.15%) and -0.31% (-0.43% to -0.19%), respectively, for CKD stage 3A (all p<0.001). For CKD stage 3B, the reduction in HbA1c for 5 mg ertugliflozin was -0.28% (-0.47% to -0.08%) (p=0.006) and for 15 mg ertugliflozin was -0.19% (-0.39% to 0.01%) (p=0.064). LS-mean placebo-adjusted reductions in body weight (range: -1.32 to -1.95 kg) and SBP (range: -2.42 to -3.41 mm Hg) were observed across CKD stage 3 categories with ertugliflozin. After an initial dip, eGFR remained above or near baseline with ertugliflozin treatment. The incidence of overall adverse events (AEs), symptomatic hypoglycemia, hypovolemia, and kidney-related AEs did not differ between ertugliflozin and placebo across CKD stage 3 subgroups. CONCLUSIONS: In VERTIS CV patients with CKD stage 3A, ertugliflozin resulted in reductions in HbA1c, body weight and SBP, maintenance of eGFR, and was generally well tolerated. Results in the CKD stage 3B subgroup were generally similar except for an attenuated HbA1c response with the 15 mg dose. TRIAL REGISTRATION NUMBER: NCT01986881. CI - (c) Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. FAU - Dagogo-Jack, Samuel AU - Dagogo-Jack S AUID- ORCID: 0000-0001-5318-9677 AD - Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA sdj@uthsc.edu. FAU - Pratley, Richard E AU - Pratley RE AUID- ORCID: 0000-0002-2912-1389 AD - AdventHealth Translational Research Institute, Orlando, Florida, USA. FAU - Cherney, David Z I AU - Cherney DZI AD - University Health Network, University of Toronto, Toronto, Ontario, Canada. FAU - McGuire, Darren K AU - McGuire DK AD - Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center and Parkland Health & Hospital System, Dallas, Texas, USA. FAU - Cosentino, Francesco AU - Cosentino F AD - Unit of Cardiology, Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden. FAU - Shih, Weichung J AU - Shih WJ AD - Department of Biostatistics, Rutgers School of Public Health and Rutgers Cancer Institute of New Jersey, Piscataway, New Jersey, USA. FAU - Liu, Jie AU - Liu J AD - Merck & Co., Inc, Kenilworth, New Jersey, USA. FAU - Frederich, Robert AU - Frederich R AD - Department of Clinical Development & Operations, Pfizer Inc, Collegeville, Pennsylvania, USA. FAU - Mancuso, James P AU - Mancuso JP AD - Global Product Development, Pfizer Inc, Groton, Connecticut, USA. FAU - Raji, Annaswamy AU - Raji A AD - Merck & Co., Inc, Kenilworth, New Jersey, USA. FAU - Gantz, Ira AU - Gantz I AD - Merck & Co., Inc, Kenilworth, New Jersey, USA. LA - eng SI - ClinicalTrials.gov/NCT01986881 PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - England TA - BMJ Open Diabetes Res Care JT - BMJ open diabetes research & care JID - 101641391 RN - 0 (Bridged Bicyclo Compounds, Heterocyclic) RN - 0 (Hypoglycemic Agents) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 6C282481IP (ertugliflozin) SB - IM MH - Bridged Bicyclo Compounds, Heterocyclic MH - *Diabetes Mellitus, Type 2/complications/drug therapy MH - Humans MH - Hypoglycemic Agents MH - *Renal Insufficiency, Chronic/complications/drug therapy MH - *Sodium-Glucose Transporter 2 Inhibitors/adverse effects MH - Treatment Outcome PMC - PMC8499340 OTO - NOTNLM OT - chronic OT - diabetes mellitus OT - drug therapy OT - glycated hemoglobin A OT - kidney failure OT - type 2 COIS- Competing interests: SD-J has led clinical trials for AstraZeneca, Boehringer Ingelheim, and Novo Nordisk; has received consulting fees from AstraZeneca, Bayer, Boehringer Ingelheim, Janssen, Merck & Co, and Sano fi ; has equity interests in Jana Care and Aerami Therapeutics; and serves on the editorial boards of The American Journal of the Medical Sciences, BMJ Open Diabetes Research & Care, Experimental Biology & Medicine, and Frontiers in Endocrinology. REP has received grants (directed to his institution) from Hanmi Pharmaceutical Co, Janssen, Metavention, Novo Nordisk, Poxel SA, and Sano fi ; has received consulting fees (directed to his institution) from AstraZeneca, Corcept Therapeutics Incorporated, Glytec, Hanmi Pharmaceutical Co, Janssen, Merck & Co, Mundipharma, Novo Nordisk, Pfizer, Sano fi , Scohia Pharma, and Sun Pharmaceutical Industries; and has received support for attending meetings/travel (directed to his institution or to the travel provider) from AstraZeneca, Glytec, Merck & Co, Mundipharma, Novo Nordisk, and Pfizer. DZIC has received consulting fees and/or speaking honoraria from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Janssen, Merck & Co, Mitsubishi-Tanabe, Novo Nordisk, Prometic, and Sanofi; and has received operating funds from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck & Co, Novo Nordisk, and Sanofi. DKM has received consulting fees from Afimmune, Applied Therapeutics, AstraZeneca, Boehringer Ingelheim, Esperion, Lexicon, Lilly USA, Merck Sharp & Dohme, Metavant, Novo Nordisk, P fi zer, and Sano fi US; has received honoraria from Boehringer Ingelheim; has received payment for expert testimony from Kirkland & Ellis on behalf of Boehringer Ingelheim; and has participated on data safety monitoring boards/advisory boards for CSL Behring, AbbVie, Eidos, Otsuka, Arena, and Akebia. FC has received research grants from the Swedish Research Council, Swedish Heart & Lung Foundation, and King Gustav V and Queen Victoria Foundation; and has received consulting fees from Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Merck Sharp & Dohme, Mundipharma, Novo Nordisk, and P fi zer. JL, AR, and IG are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, New Jersey, USA, and may own stock in Merck & Co., Inc., Kenilworth, New Jersey, USA. RF and JPM are employees of, and may own shares/stock options in, Pfizer Inc., New York, New York, USA. EDAT- 2021/10/09 06:00 MHDA- 2021/10/13 06:00 PMCR- 2021/10/07 CRDT- 2021/10/08 06:09 PHST- 2021/07/19 00:00 [received] PHST- 2021/09/11 00:00 [accepted] PHST- 2021/10/08 06:09 [entrez] PHST- 2021/10/09 06:00 [pubmed] PHST- 2021/10/13 06:00 [medline] PHST- 2021/10/07 00:00 [pmc-release] AID - 9/1/e002484 [pii] AID - bmjdrc-2021-002484 [pii] AID - 10.1136/bmjdrc-2021-002484 [doi] PST - ppublish SO - BMJ Open Diabetes Res Care. 2021 Oct;9(1):e002484. doi: 10.1136/bmjdrc-2021-002484.