Evaluating the Effects of Canagliflozin on Cardiovascular and Renal Events in Patients With Type 2 Diabetes Mellitus and Chronic Kidney Disease According to Baseline HbA1c, Including Those With HbA1c <7%: Results From the CREDENCE Trial
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Combination RAAS therapy (ACE inhibitor plus ARB, or renin inhibitor added to another RAAS blocker) does not improve survival or prevent CKD progression.
“Combination therapy with an ACE inhibitor and an ARB or with a renin inhibitor added to another RAAS-blocking agent does not prolong survival or prevent progression of CKD.263,440,441”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [441]
The correspondence (pp. 408–409) reports cardiovascular and renal outcomes for canagliflozin versus placebo, not for combination RAAS therapy. Searches for ACE inhibitor plus ARB therapy and renin-inhibitor combinations found no passage addressing whether those regimens prolong survival or prevent CKD progression. (LLM, conf=0.76)
Experimental — accuracy not yet measuredIn advanced CKD (G3b or higher), combination RAAS therapy raises hyperkalemia and AKI risk.
“In persons with advanced CKD (G3b and higher), combination therapy increases the risk of hyperkalemia and AKI and is therefore not recommended.263,441,442”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [441]
The efficacy and safety passage (p. 408) compares canagliflozin with placebo by baseline HbA1c and lists acute kidney injury as a safety outcome. The discussion (p. 409) mentions ACE inhibitors only as an analogy for treatment based on cardiovascular or renal risk. Searches for combination RAAS therapy, dual blockade, hyperkalemia, and CKD G3b found no passage addressing the attributed risk or recommendation. (LLM, conf=0.76)
Experimental — accuracy not yet measuredThe kidney benefits of SGLT2 inhibitors appear largely independent of glycemic control.
“The kidney benefits of SGLT2 inhibitors appear to be largely independent of glycemic control based on a growing series of observations.”
From SGLT2 inhibition for CKD and cardiovascular disease in type 2 diabetes: report of a scientific workshop sponsored by the National Kidney Foundation (2021) · cites this paper as [15]
SGLT2 inhibitors have kidney benefits in people with well-controlled glycemia (HbA1c below 7%) in whom further glucose lowering was minimal.
“SGLT2 inhibitors also have kidney benefits in people with well-controlled glycemia (HbA1c <7%) in whom further glucose lowering was minimal (15).”
From SGLT2 inhibition for CKD and cardiovascular disease in type 2 diabetes: report of a scientific workshop sponsored by the National Kidney Foundation (2021) · cites this paper as [15]
The cardiovascular outcome trials and CREDENCE were comparable in key aspects: type 2 diabetes participants, placebo controls, SGLT2 inhibitor dose not based on glycemia, all participants treated by standard of care, and similarly defined and adjudicated outcomes.
“The CVOTs designed to test safety and a CKD trial (CREDENCE) were comparable in key aspects: participants with T2DM, placebo controls, SGLT2 inhibitor dose not based on glycemia, all participants treated by standard of care, and similarly defined and adjudicated outcomes.”
From SGLT2 inhibition for CKD and cardiovascular disease in type 2 diabetes: report of a scientific workshop sponsored by the National Kidney Foundation (2021) · cites this paper as [15]
Diuresis is an important mechanism for reducing blood pressure and risk for heart failure events.
“Diuresis is an important mechanism for reducing blood pressure and risk for HF events (11–16,35).”
From SGLT2 inhibition for CKD and cardiovascular disease in type 2 diabetes: report of a scientific workshop sponsored by the National Kidney Foundation (2021) · cites this paper as [15]
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SGLT2 Inhibitors and Kidney Diseases: A Clinical Perspective
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- Authors
- Cannon, C. P., Perkovic, V., Agarwal, R., Baldassarre, J., Bakris, G., Charytan, D. M., de Zeeuw, D., Edwards, R., Greene, T., Heerspink, H. J. L., Jardine, M. J., Levin, A., Li, J.-W., Neal, B., Pollock, C., Wheeler, D. C., Zhang, H., Zinman, B., & Mahaffey, K. W.
- Affiliations
- Brigham and Women's Hospital (US)
- Royal North Shore Hospital (AU)
- Richard L. Roudebush VA Medical Center (US)
- Janssen Research & Development (United States) (US)
- University of Chicago (US)
- NYU Langone Health (US)
- Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, The Netherlands (D.d.Z., H.J.L.H.).
- University of Utah (US)
- University Medical Center Groningen (NL)
- Concord Repatriation General Hospital (AU)
- University of British Columbia (CA)
- UNSW Sydney (AU)
- The University of Sydney (AU)
- University College London (GB)
- Peking University First Hospital (CN)
- Mount Sinai Hospital (CA)
- Stanford Medicine (US)
- ORCID
- Venue
- Circulation
- Published
- 2020-02-04
- Volume
- 141
- Issue
- 5
- Pages
- 407-410
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W3005959108
- Cited by
- 117
- References
- 6
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 9 · 2023: 11 · 2022: 23 · 2021: 40 · 2020: 26
- FWCI
- 18.06
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- public-domain
- Locations
- Circulation (publishedVersion, public-domain)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by)
- Spiral (Imperial College London) (submittedVersion)
- Funders
- Amgen
- Bristol-Myers Squibb
- Eli Lilly and Company
- Pfizer
- AstraZeneca
- GlaxoSmithKline
- Sanofi
- Gilead Sciences
- Celgene
- University of Chicago
- University of Washington
- Regeneron Pharmaceuticals
- Ironwood Pharmaceuticals, Incorporated
- Ablynx
- MyoKardia
- Verily Life Sciences
- NxStage
- Kidney Foundation of Canada
- Novo Nordisk
- Astellas Pharma
- Servier
- Akebia Therapeutics
- National Institutes of Health
- University of California, San Francisco
- Canadian Institutes of Health Research
- Medical Research Council
- National Health and Medical Research Council
- Relypsa
- National Institute of Diabetes and Digestive and Kidney Diseases
- Janssen Pharmaceuticals
- Daiichi Sankyo Europe
- Medical Research Future Fund
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Keywords
- canagliflozin, type 2 diabetes, chronic kidney disease, cardiovascular events, renal events, HbA1c, glycemic control, SGLT2 inhibitors
- MeSH terms
- Canagliflozin, Cardiovascular System, Diabetes Mellitus, Type 2, Female, Glycated Hemoglobin, Humans, Hypoglycemic Agents, Kidney, Male, Renal Insufficiency, Chronic
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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