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

Effects of SGLT2 inhibition on insulin use in CKD and type 2 diabetes: insights from the CREDENCE trial.

Bryony Beal, Luke Buizen, Emily K Yeung, Lauren Heath, Lauren Houston, David Z I Cherney, Meg Jardine, Carol Pollock, Clare Arnott, Sradha S Kotwal and 3 more

Abstract readRandomized Controlled TrialMulticenter Study
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 2 numbers from its abstract, feeding 1 cell of the map, but none could be read as for or against, so it casts no vote. Cited by 2 papers.

2numbers the graph read from it
0cells 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.

Read, but not usablea number the graph found but could not read as for or against

Sustained insulin dose reductions of >50%canagliflozin vs placebodirection of benefit for this outcome is not defined · t2d, ckdfeeds one cell of the map
HR 1.491.15 to 1.91
Sustained insulin dose reductions of >50% were achieved more frequently with canagliflozin than placebo [HR 1.49 (95% CI 1.15-1.91)], although no difference in insulin discontinuation was observed between treatment arms.
Insulin initiation or a >25% insulin dose intensification (in those not receiving and receiving insulin at baseline, respectively)canagliflozin vs placebodirection of benefit for this outcome is not defined · t2d, ckdfeeds one cell of the map
HR 0.810.71 to 0.93
Over a median on-treatment period of 2.0 years, canagliflozin reduced the need for insulin initiation or a >25% dose intensification by 19% compared with placebo {hazard ratio [HR] 0.81 [95% confidence interval (CI) 0.71-0.93]}, irrespective of baseline kidney function or albuminuria (both P-interaction > .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.

SGLT2 inhibitors×glycemic control

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

40 readable studies in this cell: 81 favour the treatment, 11 find no difference, 4 favour the comparator.

Belief with this paper
0.92replicated · 70 families support, 6 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
NCT010326294,330 enrolled · 2009
Δ 2.79-1.57 to 7.15
NCT011374742,996 enrolled · 2010
Δ -0.46-0.59 to -0.33
NCT011956622,245 enrolled · 2010
Δ -0.61-0.76 to -0.46
NCT010956661,484 enrolled · 2010
Δ -0.59-0.76 to -0.42
NCT009688121,452 enrolled · 2009
Δ -0.01-0.11 to 0.09
NCT017190031,413 enrolled · 2012
Adjusted mean -0.33-0.56 to -0.10
NCT011066771,284 enrolled · 2010
Δ -0.62-0.76 to -0.48
NCT016060071,282 enrolled · 2012
Δ -0.59-0.81 to -0.37
NCT006732311,240 enrolled · 2008
Δ -0.45-0.59 to -0.31
NCT020991101,233 enrolled · 2014
Δ -0.43-0.60 to -0.27
NCT006609071,217 enrolled · 2008
Δ 0.00-0.11 to 0.11
NCT018093271,186 enrolled · 2013
Δ -0.46-0.66 to -0.27

This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.

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. Implementing SGLT2 Inhibitor Therapy in Line with the New NICE Guidelines for Type 2 Diabetes Management.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2026
    Review
  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

13 authors.

Bryony BealDepartment of Renal Medicine, Royal North Shore Hospital, Sydney, NSW, Australia.ORCID 0000-0002-5697-4563
Luke BuizenGeorge Institute for Global Health, University of New South Wales, Sydney, NSW, Australia.
Emily K YeungDepartment of Nephrology and Transplantation, Guy's and St Thomas' NHS Foundation Trust, London, UK.
Lauren HeathDepartment of Renal Medicine, Royal North Shore Hospital, Sydney, NSW, Australia.
Lauren HoustonGeorge Institute for Global Health, University of New South Wales, Sydney, NSW, Australia.
David Z I CherneyDepartment of Medicine, Division of Nephrology, Toronto General Hospital, Toronto, ON, Canada.
Meg JardineGeorge Institute for Global Health, University of New South Wales, Sydney, NSW, Australia.
Carol PollockDepartment of Renal Medicine, Royal North Shore Hospital, Sydney, NSW, Australia.ORCID 0000-0001-7167-6495
Clare ArnottGeorge Institute for Global Health, University of New South Wales, Sydney, NSW, Australia.ORCID 0000-0001-9370-9913
Sradha S KotwalGeorge Institute for Global Health, University of New South Wales, Sydney, NSW, Australia.
Hiddo J L HeerspinkGeorge Institute for Global Health, University of New South Wales, Sydney, NSW, Australia.ORCID 0000-0002-3126-3730
Vlado PerkovicGeorge Institute for Global Health, University of New South Wales, Sydney, NSW, Australia.
Brendon L NeuenDepartment of Renal Medicine, Royal North Shore Hospital, Sydney, NSW, Australia.ORCID 0000-0001-9276-8380

Funding

Janssen Research and Development
8 · The paper itself

Abstract

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

backgroundInsulin is a mainstay treatment for diabetes, but its use is associated with weight gain and hypoglycaemia. Data on the effects of sodium-glucose co-transporter 2 (SGLT2) inhibitors on insulin use in people with chronic kidney disease (CKD) are limited.

methodsWe conducted a post hoc analysis of the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation trial. Effects of canagliflozin versus placebo on insulin use (initiation, dose intensification, reduction and discontinuation) in people with CKD and type 2 diabetes were evaluated using Cox regression models. The primary outcome was insulin initiation or a >25% insulin dose intensification (in those not receiving and receiving insulin at baseline, respectively). Effects on kidney, cardiovascular and safety outcomes by baseline insulin use were also assessed.

resultsAmong 4401 participants, 2884 (65.5%) were receiving insulin at baseline; these participants were more likely to have lower estimated glomerular filtration rate, higher albuminuria and a longer duration of diabetes (all P < .001). Over a median on-treatment period of 2.0 years, canagliflozin reduced the need for insulin initiation or a >25% dose intensification by 19% compared with placebo {hazard ratio [HR] 0.81 [95% confidence interval (CI) 0.71-0.93]}, irrespective of baseline kidney function or albuminuria (both P-interaction > .10). Sustained insulin dose reductions of >50% were achieved more frequently with canagliflozin than placebo [HR 1.49 (95% CI 1.15-1.91)], although no difference in insulin discontinuation was observed between treatment arms. Effects of canagliflozin on kidney, cardiovascular and safety outcomes were consistent regardless of baseline insulin use (all P-interaction > .05).

conclusionsIn CKD and type 2 diabetes, canagliflozin reduces insulin use with consistent effects regardless of baseline kidney function. This supports the use of canagliflozin in people with CKD, not only for end-organ protection, but also to improve glycaemic control and reduce exposure to insulin and its associated adverse effects.

Indexed as

CanagliflozinDiabetes Mellitus, Type 2Hypoglycemic AgentsInsulinRenal Insufficiency, ChronicSodium-Glucose Transporter 2 InhibitorsAgedBlood GlucoseDouble-Blind MethodFemaleFollow-Up StudiesGlomerular Filtration RateHumansMaleMiddle AgedPrognosisBlood GlucoseCanagliflozinHypoglycemic AgentsInsulinSLC5A2 protein, humanSodium-Glucose Transporter 2Sodium-Glucose Transporter 2 InhibitorscanagliflozinCKDdiabetic kidney diseaseinsulinSGLT2 inhibitors

Identifiers

PMID40036884
PMCPMC12394126

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.