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Cited by 116Blood Pressure and Hypertension StudiesDiabetes Treatment and ManagementChronic Kidney Disease and Diabetes

The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index; none of the 32 sources its claims cite is checked for support yet.

Blood Pressure Effects of Canagliflozin and Clinical Outcomes in Type 2 Diabetes and Chronic Kidney Disease: Insights From the CREDENCE Trial

Open access
Ye, Nan, Jardine, Meg J., Oshima, Megumi, Hockham, Carinna, Heerspink, Hiddo J.L., Agarwal, Rajiv, Bakris, George, Schutte, Aletta E., Arnott, Clare, Chang, Tara I., Górriz, Jose L., Cannon, Christopher P., Charytan, David M., de Zeeuw, Dick, Levin, Adeera, Mahaffey, Kenneth W., Neal, Bruce, Pollock, Carol, Wheeler, David C., Luca Di Tanna, Gian, Cheng, Hong, Perkovic, Vlado, Neuen, Brendon L.·2021·Circulation
DOI 10.1161/circulationaha.120.048740
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Abstract

Background: People with type 2 diabetes and chronic kidney disease experience a high burden of hypertension, but the magnitude and consistency of blood pressure (BP) lowering with canagliflozin in this population are uncertain. Whether the effects of canagliflozin on kidney and cardiovascular outcomes vary by baseline BP or BP-lowering therapy is also unknown. Methods: The CREDENCE trial (Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation) randomized people with type 2 diabetes and chronic kidney disease to canagliflozin or placebo. In a post hoc analysis, we investigated the effect of canagliflozin on systolic BP across subgroups defined by baseline systolic BP, number of BP-lowering drug classes, and history of apparent treatment-resistant hypertension (BP ≥130/80 mm Hg while receiving ≥3 classes of BP-lowering drugs, including a diuretic). We also assessed whether effects on clinical outcomes differed across these subgroups. Results: The trial included 4401 participants, of whom 3361 (76.4%) had baseline systolic BP ≥130 mm Hg, and 1371 (31.2%) had resistant hypertension. By week 3, canagliflozin reduced systolic BP by 3.50 mm Hg (95% CI, –4.27 to –2.72), an effect maintained over the duration of the trial, with similar reductions across BP and BP-lowering therapy subgroups (all P interaction ≥0.05). Canagliflozin also reduced the need for initiation of additional BP-lowering agents during the trial (hazard ratio, 0.68 [95% CI, 0.61–0.75]). The effect of canagliflozin on kidney failure, doubling of serum creatinine, or death caused by kidney or cardiovascular disease (hazard ratio, 0.70 [95% CI, 0.59–0.82]) was consistent across BP and BP-lowering therapy subgroups (all P interaction ≥0.35), as were effects on other key kidney, cardiovascular, and safety outcomes. Conclusions: In people with type 2 diabetes and chronic kidney disease, canagliflozin lowers systolic BP across all BP-defined subgroups and reduces the need for additional BP-lowering agents. These findings support use of canagliflozin for end-organ protection and as an adjunct BP-lowering therapy in people with chronic kidney disease. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02065791.

Overview

Integrity signals

Registry

Crossref · 10.1161/circulationaha.120.048740

Cites

42 of 42 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

0 of 32 cited sources checked · 0 supported · 0 flagged

Show all 44 claims

  • Probably not a substantial claim. 20
  • It may state two separate claims as one. 23
  • The quote only partly states this claim. 2
33 of 33

  • The paper relies on this without support.

    Before this analysis, the magnitude and consistency of canagliflozin's systolic blood pressure-lowering effect across baseline systolic blood pressure levels, number of blood pressure-lowering drug classes, and resistant hypertension status were unclear.

    “While canagliflozin also lowered systolic BP, the magnitude and consistency of this effect across different levels of baseline systolic BP, number of BP lowering drug classes, and in patients with and without resistant hypertension, is unclear.”

  • The paper relies on this without support.

    Whether canagliflozin's effects on kidney, cardiovascular, and safety outcomes vary across these blood pressure-defined subgroups was uncertain.

    “Whether the effects of canagliflozin on kidney, cardiovascular and safety outcomes vary across these subgroups is also uncertain.”

  • The paper relies on this without support.

    Initiation of additional blood pressure-lowering agents during the trial reflects an unmet need for blood pressure lowering.

    “and reduced the need for additional blood pressure lowering agents.”
3 of 3

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Placebo initiation percentage does not match the reported count

    Major

    The reported 836 participants cannot be 61.3% of the placebo arm: Table 2 lists 2,169 placebo participants, of whom 836 would be 38.54%. The randomized arm was not smaller than that week-3 population.

    Reported 61.3 · recomputed 38.543107

  • Canagliflozin initiation percentage does not match the reported count

    Major

    The paper reports 627 participants starting an additional BP-lowering agent as 39.8%. Using the 2,172 canagliflozin participants listed in Table 2 gives 28.87%, not 39.8%; the randomized arm was not smaller than that week-3 population.

    Reported 39.8 · recomputed 28.867403

  • Region percentages use a different denominator from the table columns

    Minor

    Table 1 places 334 North American participants in the subgroup of 1,040 with systolic BP below 130 mmHg. That is 32.12%, rather than the reported 28.3%; the region percentages appear to use region totals instead of the subgroup denominators used elsewhere in the table.

    Reported 28.3 · recomputed 32.115385

  • Discussion overstates consistency across cardiovascular subgroups

    Minor

    The discussion says the cardiovascular benefits were consistent across BP-defined subgroups, but the results report evidence that benefit varied by resistant-hypertension history for one cardiovascular outcome (interaction P=0.04).

4 of 4

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Research works printed but not linked: 1

  1. 10.1681/asn.2019111168 · DOI

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Metadata

Authors
Ye, N., Jardine, M. J., Oshima, M., Hockham, C., Heerspink, H. J. L., Agarwal, R., Bakris, G., Schutte, A. E., Arnott, C., Chang, T. I., Górriz, J. L., Cannon, C. P., Charytan, D. M., de Zeeuw, D., Levin, A., Mahaffey, K. W., Neal, B., Pollock, C., Wheeler, D. C., Luca Di Tanna, G., Cheng, H., Perkovic, V., & Neuen, B. L.
Affiliations
  • Capital Medical University (CN)
  • Concord Repatriation General Hospital (AU)
  • Kanazawa University (JP)
  • UNSW Sydney (AU)
  • University Medical Center Groningen (NL)
  • Richard L. Roudebush VA Medical Center (US)
  • University of Chicago (US)
  • Royal Prince Alfred Hospital (AU)
  • Stanford Medicine (US)
  • Department of Nephrology, Hospital Clínico Universitario, Valencia, Spain (J.L.G.).
  • Brigham and Women's Hospital (US)
  • NYU Langone Health (US)
  • Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, The Netherlands (H.J.L.H., D.d.Z.).
  • University of British Columbia (CA)
  • The University of Sydney (AU)
  • The George Institute for Global Health (GB)
  • The George Institute for Global Health (N.Y., M.J.J., M.O., C.H., A.E.S., C.A., B.N., D.C.W., G.L.D.T., V.P., B.L.N.), University of New South Wales, Sydney, Australia.
  • Royal North Shore Hospital (AU)
ORCID
Venue
Circulation
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2021-05-04
Volume
143
Issue
18
Pages
1735-1749
ISSN
  • 0009-7322 (ISSN-L)
  • 1524-4539
DOI
10.1161/circulationaha.120.048740
OpenAlex
W3126553617
Semantic Scholar
737a7cef38e8d90b20d17272ac016a6f4c544266
Cited by
115
References
39
Citations by year
2026: 5 · 2025: 30 · 2024: 20 · 2023: 23 · 2022: 23 · 2021: 14
FWCI
13.41
Type
journal article
Language
en
Open access
Licence
public-domain
Locations
  • Circulation (publishedVersion, public-domain)
  • PubMed (publishedVersion)
  • UNSWorks (University of New South Wales, Sydney, Australia) (submittedVersion, cc-by-nc-nd)
  • Spiral (Imperial College London) (submittedVersion, public-domain)
  • UCL Discovery (University College London) (submittedVersion)
  • University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
  • IUScholarWorks (Indiana University) (submittedVersion)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
Keywords
canagliflozin, type 2 diabetes, chronic kidney disease, hypertension, systolic blood pressure, resistant hypertension, blood pressure-lowering therapy, SGLT2 inhibitors, renal failure, cardiovascular outcomes, CREDENCE trial, subgroup analysis, diuretics, renal outcomes, safety outcomes, adverse events, hypoglycemia
MeSH terms
Canagliflozin, Sodium-Glucose Transporter 2 Inhibitors, Diabetes Mellitus, Type 2, Female, Humans, Male, Middle Aged, Renal Insufficiency, Chronic

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