Evidence map›Paper›PMID 31399845›Full record

Trial reportDiabetologia2019

Canagliflozin and fracture risk in individuals with type 2 diabetes: results from the CANVAS Program.

Zien Zhou, Meg Jardine, Vlado Perkovic, David R Matthews, Kenneth W Mahaffey, Dick de Zeeuw, Greg Fulcher, Mehul Desai, Richard Oh, Roger Simpson and 2 more

2 registry-linked trialsOpen access · hybridFull text readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Diabetologia, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT01032629. Cited by 34 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 1 pooled it
6.9field-weighted citation impact, top 2% 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.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · 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.

NCT01032629 phase3completed

A Randomized, Multicenter, Double-Blind, Parallel, Placebo-Controlled Study of the Effects of JNJ-28431754 on Cardiovascular Outcomes in Adult Subjects With Type 2 Diabetes Mellitus

Ran2009Enrolled4,330Registered outcomes13Posted comparisons33ConditionsCardiovascular Diseases, Diabetes Mellitus, Type 2, Risk FactorsArmsCanagliflozin (JNJ-28431754) 100 mg, Canagliflozin (JNJ-28431754) 300 mg, Placebo
Open the trial in the graph
NCT01989754 phase4completed

A Randomized, Multicenter, Double-Blind, Parallel, Placebo-Controlled Study of the Effects of Canagliflozin on Renal Endpoints in Adult Subjects With Type 2 Diabetes Mellitus

Ran2014Enrolled5,813Registered outcomes3Posted comparisons3ConditionsAlbuminuria, Diabetes Mellitus, Type 2ArmsCanagliflozin, 100 mg, Canagliflozin, 300 mg, Placebo
Open the trial in the graph
3 · Its place in the literature

Who cites it

34 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.

  1. Pooled it
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  5. Association between SGLT2 inhibitor use and the risk of vertebral augmentation after initial osteoporotic vertebral fracture in patients with type 2 diabetes.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2026
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  6. Review
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  12. Fractures in women with type 2 diabetes are associated with marked deficits in cortical parameters and trabecular plates.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2024
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4 · The record

Corrections and comments

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

5 · Who and what money

Authors and funding

12 authors at 10 institutions in 5 countries.

Zien ZhouThe George Institute for Global Health, UNSW Sydney, Level 5, 1 King St, Newtown, Sydney, NSW, 2042, Australia.
Meg JardineThe George Institute for Global Health, UNSW Sydney, Level 5, 1 King St, Newtown, Sydney, NSW, 2042, Australia.
Vlado PerkovicThe George Institute for Global Health, UNSW Sydney, Level 5, 1 King St, Newtown, Sydney, NSW, 2042, Australia.
David R MatthewsOxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK.
Kenneth W MahaffeyStanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Dick de ZeeuwUniversity of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Greg FulcherThe Royal North Shore Hospital and University of Sydney, Sydney, NSW, Australia.
Mehul DesaiJanssen Research & Development, LLC, Raritan, NJ, USA.
Richard OhJanssen Research & Development, LLC, Raritan, NJ, USA.
Roger SimpsonJanssen Research & Development, LLC, Raritan, NJ, USA.
Nelson B WattsUniversity of Cincinnati, Cincinnati, OH, USA.
Bruce NealThe George Institute for Global Health, UNSW Sydney, Level 5, 1 King St, Newtown, Sydney, NSW, 2042, Australia. bneal@georgeinstitute.org.au.
Janssen (United States) · USCenter for Clinical Research (United States) · USConcord Repatriation General Hospital · AUImperial College London · GBShanghai Jiao Tong University · CNUniversity of Cincinnati · USUniversity of Groningen · NLUniversity of Oxford · GBUniversity of Sydney · AUUNSW Sydney · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aims/hypothesisAn increased risk of fracture with canagliflozin vs placebo was reported from the CANagliflozin cardioVascular Assessment Study (CANVAS) Program, with heterogeneity of findings identified between the two trials that comprise the CANVAS Program, CANVAS and CANVAS-R. The objective of these analyses was to identify reasons for the possibly different effects on fracture observed between CANVAS and CANVAS-R.

methodsThis study was an analysis of two highly similar trials, CANVAS and CANVAS-R, conducted in 10,142 individuals with type 2 diabetes and history or high risk of cardiovascular disease who received canagliflozin (pooled 100/300 mg once daily) or placebo. Outcomes assessed in this analysis were effects on adjudicated fractures overall and by type, location, association with a fall, dose and follow-up time.

resultsA total of 496 participants recorded ≥1 fracture event during follow-up (15.40 vs 11.93 per 1000 patient-years with canagliflozin vs placebo; HR 1.26 [95% CI 1.04, 1.52]). There was significant heterogeneity in the effects on fracture (p = 0.005) between CANVAS (n = 4330: HR 1.55 [95% CI 1.21, 1.97]) and CANVAS-R (n = 5812: HR 0.86 [95% CI 0.62, 1.19]). The between-study heterogeneity in fracture risk was not clearly explained by differences in baseline characteristics, interactions of randomised treatment with participant characteristics, dose effects, duration of follow-up, metabolic effects, adverse events related to falls or adverse events possibly causing falls. CONCLUSIONS/

interpretationThere was no evidence to explain clearly the fracture risk observed in the CANVAS Program or the heterogeneity in fracture risk between the two studies. The recently reported null result for fracture in the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial suggests that the observed association in CANVAS is likely to be a chance finding, although an unidentified fall-related mechanism remains a possibility.

trial registrationClinicalTrials.gov NCT01032629, NCT01989754.

Indexed as

AgedCanagliflozinDiabetes Mellitus, Type 2FemaleFractures, BoneHumansMaleMiddle AgedSingle-Blind MethodSodium-Glucose Transporter 2 InhibitorsCanagliflozinSodium-Glucose Transporter 2 InhibitorsCanagliflozinCANVAS ProgramFractureSodium glucose co-transporter 2 inhibitorsType 2 diabetes mellitus

Identifiers

PMID31399845
PMCPMC6731200
OpenAlexW2967353121

What OpenQuestion holds

Textfull text, public
LicenceCC BY
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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 OpenQuestion graph.