Evidence map›Paper›PMID 32537887›Full record

Trial reportJournal of diabetes investigation2020

Secondary analyses to assess the profound effects of empagliflozin on endothelial function in patients with type 2 diabetes and established cardiovascular diseases: The placebo-controlled double-blind randomized effect of empagliflozin on endothelial function in cardiovascular high risk diabetes mellitus: Multi-center placebo-controlled double-blind randomized trial.

Atsushi Tanaka, Michio Shimabukuro, Noritaka Machii, Hiroki Teragawa, Yosuke Okada, Kosuke R Shima, Toshinari Takamura, Isao Taguchi, Itaru Hisauchi, Shigeru Toyoda and 6 more

Open access · goldAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal of diabetes investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed, 3 pooled it
2.1field-weighted citation impact, top 11% 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.

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

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 3 syntheses or guidelines pooled it, 22 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Trial
  5. Trial
  6. Trial
  7. Trial
  8. Trial
  9. Review
  10. Review
  11. Review
  12. Review
  13. Observational
  14. Review
  15. Review
  16. Article
  17. Review
  18. Article
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

16 authors at 12 institutions in 1 country.

Atsushi TanakaDepartment of Cardiovascular Medicine, Saga University, Saga, Japan.ORCID https://orcid.org/0000-0003-3352-7661
Michio ShimabukuroDepartment of Diabetes, Endocrinology, and Metabolism, Fukushima Medical University, Fukushima, Japan.
Noritaka MachiiDepartment of Diabetes, Endocrinology, and Metabolism, Fukushima Medical University, Fukushima, Japan.
Hiroki TeragawaDepartment of Cardiovascular Medicine, JR Hiroshima Hospital, Hiroshima, Japan.
Yosuke OkadaFirst Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
Kosuke R ShimaDepartment of Endocrinology and Metabolism, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.ORCID https://orcid.org/0000-0002-8523-6092
Toshinari TakamuraDepartment of Endocrinology and Metabolism, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.ORCID https://orcid.org/0000-0002-4393-3244
Isao TaguchiDepartment of Cardiology, Dokkyo Medical University Saitama Medical Center, Koshigaya, Japan.
Itaru HisauchiDepartment of Cardiology, Dokkyo Medical University Saitama Medical Center, Koshigaya, Japan.
Shigeru ToyodaDepartment of Cardiovascular Medicine, Dokkyo Medical University School of Medicine, Tochigi, Japan.
Yasushi MatsuzawaDivision of Cardiology, Yokohama City University Medical Center, Yokohama, Japan.
Hirofumi TomiyamaDepartment of Cardiology, Tokyo Medical University, Tokyo, Japan.
Minako Yamaoka-TojoDepartment of Rehabilitation, Kitasato University School of Allied Health Sciences, Sagamihara, Japan.
Shinichiro UedaDepartment of Clinical Pharmacology and Therapeutics, University of the Ryukyus, Nishihara, Japan.
Yukihito HigashiDepartment of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
Koichi NodeDepartment of Cardiovascular Medicine, Saga University, Saga, Japan.
Dokkyo Medical University Saitama Medical Center · JPFukushima Medical University · JPKanazawa University · JPSaga University · JPDokkyo Medical University · JPHiroshima General Hospital · JPHiroshima University · JPKitasato University · JPTokyo Medical University · JPUniversity of Occupational and Environmental Health Japan · JPUniversity of the Ryukyus · JPYokohama City University Medical Center · JP

Funding

Boehringer IngelheimEli Lilly and CompanyUehara Memorial Foundation
6 · The paper itself

Abstract

AIMS/

introductionRecent clinical trials on sodium-glucose cotransporter 2 inhibitors showed improved outcomes in patients with type 2 diabetes at a high risk of cardiovascular events. However, the underlying effects on endothelial function remain unclear. MATERIALS AND

methodsThe effect of empagliflozin on endothelial function in cardiovascular high risk diabetes mellitus: Multi-center placebo-controlled double-blind randomized (EMBLEM) trial in patients with type 2 diabetes and cardiovascular disease showed empagliflozin treatment for 24 weeks had no effect on peripheral endothelial function measured by reactive hyperemia peripheral arterial tonometry. This post-hoc analysis of the EMBLEM trial included a detailed evaluation of the effects of empagliflozin on peripheral endothelial function in order to elucidate the clinical characteristics of responders or non-responders to treatment.

resultsOf the 47 patients randomized into the empagliflozin group, 21 (44.7%) showed an increase in the reactive hyperemia index (RHI) after 24 weeks of intervention, with no apparent difference in the clinical characteristics between patients whose RHI either increased (at least >0) or did not increase. There was also no obvious difference between the treatment groups in the proportion of patients who had a clinically meaningful change (≥15%) in log-transformed RHI. No correlation was found between changes in RHI and clinical variables, such as vital signs and laboratory parameters.

conclusionsTreatment with empagliflozin for 24 weeks in patients with type 2 diabetes and cardiovascular disease did not affect peripheral endothelial function, and was not related to changes in clinical variables, including glycemic parameters. These findings suggest that the actions of sodium-glucose cotransporter 2 inhibitors other than direct improvement in peripheral endothelial function were responsible, at least in the early phase, for the clinical benefits found in recent cardiovascular outcome trials.

Indexed as

AgedBenzhydryl CompoundsBiomarkersBlood GlucoseCardiovascular DiseasesDiabetes Mellitus, Type 2Double-Blind MethodEndothelium, VascularFemaleFollow-Up StudiesGlucosidesGlycated HemoglobinHumansMaleMiddle AgedPrognosisBenzhydryl CompoundsBiomarkersBlood GlucoseempagliflozinGlucosidesGlycated Hemoglobinhemoglobin A1c protein, humanSodium-Glucose Transporter 2 InhibitorsCardiovascular diseaseEmpagliflozinEndothelial function

Identifiers

PMID32537887
PMCPMC7610132
OpenAlexW3035277190

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.