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Effects of canagliflozin on anaemia in patients with type 2 diabetes and chronic kidney disease: a post-hoc analysis from the CREDENCE trial
Open accessAbstract
BACKGROUND: Sodium-glucose co-transporter 2 inhibitors might enhance erythropoiesis and increase red blood cell mass. We assessed the long-term effects of canagliflozin on anaemia-related outcomes. METHODS: In a post-hoc analysis of the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial, we included patients with type 2 diabetes and chronic kidney disease who were randomly assigned to treatment with canagliflozin or placebo at 690 sites in 34 countries. We assessed the effects of canagliflozin versus matched placebo on haemoglobin and haematocrit using linear mixed-effects models. The primary outcome of this post-hoc analysis was a composite outcome of investigator-reported anaemia or treatment for anaemia, which was assessed using Kaplan-Meier analysis and Cox regression models. All analyses were done by intention to treat. FINDINGS: Between March 24, 2014, and May 5, 2017, 4401 participants were randomly assigned to receive canagliflozin (100 mg; n=2202) or placebo (n=2199). At baseline, mean haemoglobin concentration was 132·0 g/L (SD 17·7), 1599 (36%) of 4401 participants had anaemia (defined as haemoglobin <130 g/L in men or <120 g/L in women), and 33 (<1%) of 4401 participants used erythropoiesis-stimulating agents. During a median follow-up period of 2·6 years (IQR 2·1-3·1), mean haemoglobin concentration was 7·1 g/L (95% CI 6·4-7·8) higher and haematocrit was 2·4% (2·2-2·6) higher in the canagliflozin group than the placebo group. Overall, 573 of 4401 participants had either an investigator-reported anaemia event or initiation of treatment for anaemia: 358 (8%) of 4401 participants reported anaemia events, 343 (8%) initiated iron preparations, 141 (3%) initiated erythropoiesis-stimulating agents, and 114 (2%) received blood transfusion. The risk of the composite outcome of anaemia events or initiation of treatment for anaemia was lower in the canagliflozin group than the placebo group (hazard ratio 0·65, 95% CI 0·55-0·77; p<0·0001). Compared with the placebo group, participants in the canagliflozin group also had lower risks of anaemia events alone (0·58, 0·47-0·72; p<0·0001), initiation of iron preparations (0·64, 0·52-0·80; p<0·0001), and need for erythropoiesis-stimulating agents (0·65, 0·46-0·91; p=0·012). INTERPRETATION: These data suggest that canagliflozin reduces the risk of anaemia-associated outcomes, including the need for erythropoiesis-stimulating agents, among patients with type 2 diabetes and chronic kidney disease. FUNDING: Janssen Research and Development.
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“It is therefore perhaps not a surprise that in a large multi-national kidney outcome trial with canagliflozin (namely, the CREDENCE trial), the risk of anemia, which was an independent predictor of renal and cardiovascular outcomes, and initiation of treatments for anemia were markedly reduced with canagliflozin (Oshima et al., 2020).”
From A kidney perspective on the mechanism of action of sodium glucose co-transporter 2 inhibitors (2021) · cites this paper as Oshima et al., 2020
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Metadata
- Authors
- Oshima, M., Neuen, B. L., Jardine, M. J., Bakris, G., Edwards, R., Levin, A., Mahaffey, K. W., Neal, B., Pollock, C., Rosenthal, N., Wada, T., Wheeler, D. C., Perkovic, V., & Heerspink, H. J. L.
- Affiliations
- Kanazawa University (JP)
- UNSW Sydney (AU)
- Concord Repatriation General Hospital (AU)
- University of Chicago (US)
- Janssen Research & Development (United States) (US)
- University of British Columbia (CA)
- Stanford Medicine (US)
- The University of Sydney (AU)
- The George Institute for Global Health (GB)
- Royal North Shore Hospital (AU)
- University Medical Center Groningen (NL)
- Corresponding author
- Heerspink, Hiddo J L
- ORCID
- Venue
- The Lancet Diabetes & Endocrinology
- Publisher
- Elsevier BV
- Published
- 2020-11
- Volume
- 8
- Issue
- 11
- Pages
- 903-914
- ISSN
- 2213-8587 (ISSN-L)
- OpenAlex
- W3093341334
- Cited by
- 135
- References
- 30
- Citations by year
- 2026: 15 · 2025: 17 · 2024: 26 · 2023: 28 · 2022: 20 · 2021: 29
- FWCI
- 12.16
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Lancet Diabetes & Endocrinology (publishedVersion, public-domain)
- PubMed (publishedVersion)
- UNSWorks (University of New South Wales, Sydney, Australia) (submittedVersion, cc-by-nc-nd)
- UCL Discovery (University College London) (submittedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Spiral (Imperial College London) (submittedVersion, cc-by-nc-nd)
- Funders
- Janssen Research and Development
- Janssen Scientific Affairs
- National Health and Medical Research Council
- University of New South Wales
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- Topics
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Keywords
- canagliflozin, anemia, type 2 diabetes, chronic kidney disease, SGLT2 inhibitors, hemoglobin, hematocrit, erythropoiesis, iron supplementation, erythropoiesis-stimulating agents, CREDENCE trial, renal outcomes, haemoglobin decline, iron deficiency, iron overload
- MeSH terms
- Canagliflozin, Sodium-Glucose Transporter 2 Inhibitors, Aged, Anemia, Diabetes Mellitus, Type 2, Double-Blind Method, Female, Follow-Up Studies, Humans, Male, Middle Aged, Treatment Outcome, Renal Insufficiency, Chronic
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