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
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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.
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The ability of SGLT2 inhibitors to lower glucose levels declines when the eGFR falls below 45 mL/min/1.73 m2.
“However, their ability to lower glucose levels declines when the eGFR falls below 45 mL/min/1.73m 2 (142-144).”
From 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025 (2025) · cites this paper as [143]
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Cites
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Dapagliflozin in Patients with Chronic Kidney Disease
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Cited by
Sorted by citations
9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2025
American Diabetes Association Professional Practice Committee, ElSayed, N. A., McCoy, R. G., Aleppo, G., Bajaj, M., Balapattabi, K., Beverly, E. A., Briggs Early, K., Bruemmer, D., Echouffo-Tcheugui, J. B., et al. (2025) · Diabetes Care · doi:10.2337/dc25-s009 · Cited by 728 · see citing works
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- Authors
- Dagogo-Jack, S., Pratley, R. E., Cherney, D. Z. I., McGuire, D. K., Cosentino, F., Shih, W. J., Liu, J., Frederich, R., Mancuso, J. P., Raji, A., & Gantz, I.
- Affiliations
- University of Tennessee Health Science Center (US)
- AdventHealth Orlando (US)
- University Health Network (CA)
- Parkland Health & Hospital System (US)
- Karolinska University Hospital (SE)
- Rutgers, The State University of New Jersey (US)
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Pfizer (United States) (US)
- Corresponding author
- Dagogo-Jack, Samuel
- ORCID
- Venue
- BMJ Open Diabetes Research & Care
- Publisher
- BMJ
- Published
- 2021-10
- Volume
- 9
- Issue
- 1
- Pages
- e002484
- ISSN
- 2052-4897 (ISSN-L)
- PMC
- PMC8499340
- OpenAlex
- W3202291872
- Cited by
- 37
- References
- 2
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 10 · 2023: 8 · 2022: 4
- FWCI
- 4.11
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- BMJ Open Diabetes Research & Care (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA (Not applicable; general funding of clinical trial)
- Pfizer Inc., New York, NY, USA (Not applicable; general funding of clinical trial)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- ertugliflozin, SGLT2 inhibitors, type 2 diabetes, chronic kidney disease stage 3, HbA1c, cardiovascular outcomes, body weight, systolic blood pressure, EGFR, adverse events, hypoglycemia, hypovolemia, dose comparison
- MeSH terms
- Sodium-Glucose Transporter 2 Inhibitors, Diabetes Mellitus, Type 2, Humans, Hypoglycemic Agents, Treatment Outcome, Bridged Bicyclo Compounds, Heterocyclic, Renal Insufficiency, Chronic
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