Evidence map›SGLT2 inhibitors × cardiovascular events›PMID 33874750›Full record

Trial reportStroke2021

Effect of SGLT2 Inhibitors on Stroke and Atrial Fibrillation in Diabetic Kidney Disease: Results From the CREDENCE Trial and Meta-Analysis.

Zien Zhou, Meg J Jardine, Qiang Li, Brendon L Neuen, Christopher P Cannon, Dick de Zeeuw, Robert Edwards, Adeera Levin, Kenneth W Mahaffey, Vlado Perkovic and 3 more

Registry-linked trialOpen access · hybridAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Stroke, 2021. The graph read 1 number from its abstract, feeding 1 cell of the map, but it casts no vote: it is a later paper about NCT02065791, whose primary report (PMID 30990260) speaks for the trial. It reports registered trial NCT02065791. Cited by 62 papers, 10 of them syntheses that pooled it.

1number the graph read from it
0cells of the map it votes in
62citing papers in PubMed, 10 pooled it
14.2field-weighted citation impact, top 1% of its field
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 eventsno clear difference · against placebo · arrhythmia, t2dfeeds one cell of the map
HR 0.770.55 to 1.08
RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]).
FeedsSGLT2 inhibitors×cardiovascular events

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×cardiovascular events

Does not voteOpen 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’s trial, registry resultNCT02065791 · 4,401 enrolled · 2014
HR 0.700.59 to 0.82
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
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
NCT043636972,401 enrolled · 2020
HR 0.860.68 to 1.08
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.

NCT02065791 phase3completed

A Randomized, Double-blind, Event-driven, Placebo-controlled, Multicenter Study of the Effects of Canagliflozin on Renal and Cardiovascular Outcomes in Subjects With Type 2 Diabetes Mellitus and Diabetic Nephropathy

Ran2014Enrolled4,401Registered outcomes8Posted comparisons8ConditionsDiabetes Mellitus, Type 2, Diabetic NephropathyArmsCanagliflozin, Placebo
Open the trial in the graph
5 · Its place in the literature

Who cites it

62 citing papers in PubMed, 10 syntheses or guidelines pooled it, 114 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. Pooled it
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  9. Pooled it
  10. Pooled it
  11. Article
  12. Review
  13. Article
  14. Review
  15. Observational
  16. Article
  17. Review
  18. Sodium-glucose cotransporter 2 inhibitors and atherosclerosis.American journal of preventive cardiology · 2025
    Review
  19. The Role of Diabetes and SGLT2 Inhibitors in Cerebrovascular Diseases.Current neurology and neuroscience reports · 2025
    Review
  20. Review

2 more citing papers are in PubMed but not listed here.

6 · The record

Corrections and comments

7 · Who and what money

Authors and funding

13 authors at 13 institutions in 6 countries.

Zien ZhouThe George Institute for Global Health, UNSW Sydney, Australia (Z.Z., M.J.J., Q.L., B.L.N., V.P., B.N.).
Meg J JardineThe George Institute for Global Health, UNSW Sydney, Australia (Z.Z., M.J.J., Q.L., B.L.N., V.P., B.N.).
Qiang LiThe George Institute for Global Health, UNSW Sydney, Australia (Z.Z., M.J.J., Q.L., B.L.N., V.P., B.N.).
Brendon L NeuenThe George Institute for Global Health, UNSW Sydney, Australia (Z.Z., M.J.J., Q.L., B.L.N., V.P., B.N.).
Christopher P CannonCardiovascular Division, Brigham and Women's Hospital and Baim Institute for Clinical Research, Boston, MA (C.P.C.).
Dick de ZeeuwDepartment of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, the Netherlands (D.d.Z.).
Robert EdwardsJanssen Research & Development, LLC, Raritan, NJ (R.E.).
Adeera LevinDivision of Nephrology, University of British Columbia, Vancouver, BC, Canada (A.L.).
Kenneth W MahaffeyStanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, CA (K.W.M.).
Vlado PerkovicThe George Institute for Global Health, UNSW Sydney, Australia (Z.Z., M.J.J., Q.L., B.L.N., V.P., B.N.).
Bruce NealThe George Institute for Global Health, UNSW Sydney, Australia (Z.Z., M.J.J., Q.L., B.L.N., V.P., B.N.).
Richard I LindleyWestmead Applied Research Centre, University of Sydney, Sydney, Australia (R.I.L.).
CREDENCE Trial Investigators*
Janssen (United States) · USStanford Medicine · USThe George Institute for Global Health · AUBrigham and Women's Hospital · USCenter for Clinical Research (United States) · USConcord Repatriation General Hospital · AUGeorge Institute for Global Health · CNRoyal North Shore Hospital · AUShanghai Jiao Tong University · CNThe George Institute for Global Health · GBThe University of Sydney · AUUniversity Medical Center Groningen · NLUniversity of British Columbia · CA

Funding

No grant is acknowledged in the PubMed record.

8 · The paper itself

Abstract

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

background and purposeChronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus.

methodsCREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-analysis.

resultsIn CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: total stroke (HR

conclusionsAlthough we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02065791.

Indexed as

Atrial FibrillationCanagliflozinDiabetes Mellitus, Type 2Diabetic NephropathiesHumansMeta-Analysis as TopicSodium-Glucose Transporter 2 InhibitorsStrokeCanagliflozinSodium-Glucose Transporter 2 Inhibitorsatrial fibrillationcanagliflozinglomerular filtration ratehemorrhagic strokeischemic stroke

Identifiers

PMID33874750
PMCPMC8078131
OpenAlexW3154580191

What Socratic holds

Texttitle and abstract
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

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.