Trial reportNephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association2025

Canagliflozin and iron metabolism in the CREDENCE trial.

Akihiko Koshino, Hiddo J L Heerspink, Niels Jongs, Sunil V Badve, Clare Arnott, Bruce Neal, Meg Jardine, Kenneth W Mahaffey, Carol Pollock, Vlado Perkovic and 4 more

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2025. The graph read 1 number from its abstract, feeding 2 cells of the map: it . Cited by 2 papers.

1number the graph read from it
2cells of the map it votes in
2citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

← favours the treatmentfavours the comparator →
0.51 · no effect
Cardiovascular eventsfavours the treatment · head-to-head · t2d, ckdfeeds 2 cells of the map
HR 0.700.56 to 0.87
The relative effect of canagliflozin on the primary outcome of doubling of serum creatinine, kidney failure or death due to cardiovascular disease or kidney failure (hazard ratio 0.70, 95% CI 0.56, 0.87) was consistent regardless of iron deficiency (P for interaction = .83), as were effects on other cardiovascular and mortality outcomes (all P for interactions ≥0.10).

clause the extractor read what became the number

2 · Its place on the map

Where it lands on the map

Rows are treatments, columns are outcomes. The coloured squares are the cells this paper feeds, coloured by the vote it casts there. Click one to jump to what this paper adds to it.

supports the treatmentfavours the comparatorno clear differenceread, but no usable result
3 · What it changes

What it adds to each cell

For every cell the paper feeds: the belief in the claim with and without this paper, and this paper's estimate drawn against every other readable study in the cell. The ringed dot is this paper.

Other cardiovascular drugs×cardiovascular events

No readable resultOpen on the map →What to test next →

2 readable studies in this cell: 1 favour the treatment, 1 find no difference, 0 favour the comparator.

Belief with this paper
0.25no deciding trial · 0 families support, 0 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
1 · no effect
This paper · 2025
HR 0.700.56 to 0.87

SGLT2 inhibitors×cardiovascular events

No readable resultOpen on the map →What to test next →

22 readable studies in this cell: 9 favour the treatment, 11 find no difference, 2 favour the comparator.

Belief with this paper
0.50contested · 9 families support, 6 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
1 · no effect
This paper · 2025
HR 0.700.56 to 0.87
NCT0546531762,197 enrolled · 2022
HR 0.750.65 to 0.86
NCT0399313226,774 enrolled · 2018
HR 1.010.91 to 1.11
NCT0173053417,190 enrolled · 2013
HR 0.930.84 to 1.03
NCT0493781616,746 enrolled · 2021
HR 1.000.83 to 1.20
NCT045096746,522 enrolled · 2020
HR 0.900.76 to 1.06
NCT036192136,263 enrolled · 2018
HR 0.820.73 to 0.92
NCT030579515,988 enrolled · 2017
HR 0.790.69 to 0.90
NCT019897545,813 enrolled · 2014
HR 0.720.55 to 0.94
NCT020657914,401 enrolled · 2014
HR 0.700.59 to 0.82
NCT010326294,330 enrolled · 2009
HR 0.930.78 to 1.12
NCT045647424,017 enrolled · 2020
Win Ratio (WR) 1.341.20 to 1.50
NCT030579773,730 enrolled · 2017
HR 0.750.65 to 0.86
4 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

5 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. KDIGO 2026 Clinical Practice Guideline for Anemia in Chronic Kidney Disease (CKD): a commentary from the European Renal Best Practice (ERBP).Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2026
    Article
  2. Review
6 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

7 · Who and what money

Authors and funding

14 authors.

Akihiko KoshinoDepartment of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.ORCID 0000-0002-9432-2427
Hiddo J L HeerspinkDepartment of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.ORCID 0000-0002-3126-3730
Niels JongsDepartment of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Sunil V BadveThe George Institute for Global Health, UNSW Sydney, Sydney, Australia.
Clare ArnottThe George Institute for Global Health, UNSW Sydney, Sydney, Australia.ORCID 0000-0001-9370-9913
Bruce NealThe George Institute for Global Health, UNSW Sydney, Sydney, Australia.
Meg JardineThe George Institute for Global Health, UNSW Sydney, Sydney, Australia.
Kenneth W MahaffeyStanford Center for Clinical Research, Stanford University School of Medicine, Stanford, CA, USA.
Carol PollockKolling Institute of Medical Research, Sydney Medical School, University of Sydney, Sydney, Australia.ORCID 0000-0001-7167-6495
Vlado PerkovicThe George Institute for Global Health, UNSW Sydney, Sydney, Australia.
Michael K HansenJanssen Research & Development, LLC, Spring House, PA, USA.
Stephan J L BakkerDepartment of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Takashi WadaDepartment of Nephrology and Rheumatology, Kanazawa University, Ishikawa, Japan.
Brendon L NeuenThe George Institute for Global Health, UNSW Sydney, Sydney, Australia.ORCID 0000-0001-9276-8380

Funding

Janssen Research and DevelopmentMitsubishi Tanabe Pharm
8 · The paper itself

Abstract

The marked sentences are the ones the graph read a number from.

backgroundStudies in patients with heart failure have indicated that sodium-glucose cotransporter 2 (SGLT2) inhibitors increase iron use and enhance erythropoiesis. In this post hoc analysis of the Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial, we evaluated the effects of canagliflozin on iron metabolism in patients with chronic kidney disease (CKD) and whether the effects of canagliflozin on hemoglobin and cardiorenal outcomes were modified by iron deficiency.

methodsWe measured serum iron, total iron binding capacity (TIBC), transferrin saturation (TSAT) and ferritin at baseline and 12 months. The effects of canagliflozin, relative to placebo, on iron markers were assessed with analysis of covariance. Interactions between baseline iron deficiency, defined as TSAT <20%, and the effects of canagliflozin on hemoglobin and cardiorenal outcomes were evaluated with mixed effect models and Cox regression models, respectively.

resultsOf 4401 participants randomized in CREDENCE, 2416 (54.9%) had iron markers measured at baseline, of whom 924 (38.2%) were iron deficient. Canagliflozin, compared with placebo, increased TIBC by 2.1% [95% confidence interval (CI) 0.4, 3.8; P = .014] and decreased ferritin by 11.5% (95% CI 7.1, 15.7; P < .001) with no clear effect on serum iron or TSAT. Canagliflozin increased hemoglobin over the trial duration by 7.3 g/L (95% CI 6.2, 8.5; P < .001) and 6.7 g/L (95% CI 5.2, 8.2; P < .001) in patients with and without iron deficiency, respectively (P for interaction = .38). The relative effect of canagliflozin on the primary outcome of doubling of serum creatinine, kidney failure or death due to cardiovascular disease or kidney failure (hazard ratio 0.70, 95% CI 0.56, 0.87) was consistent regardless of iron deficiency (P for interaction = .83), as were effects on other cardiovascular and mortality outcomes (all P for interactions ≥0.10).

conclusionIron deficiency is highly prevalent in patients with type 2 diabetes and CKD. Canagliflozin increased TIBC and decreased ferritin in patients with type 2 diabetes and CKD, suggesting increased iron utilization, and improved hemoglobin levels and clinical outcomes regardless of iron deficiency.

Indexed as

CanagliflozinDiabetes Mellitus, Type 2IronRenal Insufficiency, ChronicSodium-Glucose Transporter 2 InhibitorsAgedBiomarkersDouble-Blind MethodFemaleFollow-Up StudiesGlomerular Filtration RateHumansMaleMiddle AgedPrognosisBiomarkersCanagliflozinIronSodium-Glucose Transporter 2 Inhibitorsanemiacardiovascularchronic kidney diseaseiron deficiencysodium-glucose cotransporter 2 inhibitors

Identifiers

PMID39304530
PMCPMC11960735

What Socratic holds

Texttitle and abstract
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.