Evidence map›Paper›PMID 34278803›Full record

Trial reportJournal of the American Heart Association2021

Effects of Empagliflozin on Myocardial Flow Reserve in Patients With Type 2 Diabetes Mellitus: The SIMPLE Trial.

Mikkel Jürgens, Morten Schou, Philip Hasbak, Andreas Kjær, Emil Wolsk, Bo Zerahn, Mikkel Wiberg, Niels H Brandt-Jacobsen, Peter Gæde, Peter Rossing and 4 more

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in Journal of the American Heart Association, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
–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.

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

16 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Trial
  3. Trial
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  5. Trial
  6. Coronary microvascular dysfunction: a narrative review.Cardiovascular diagnosis and therapy · 2026
    Review
  7. Review
  8. Article
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  13. Coronary microvascular dysfunction in heart failure patients.Frontiers in cardiovascular medicine · 2023
    Review
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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

14 authors.

Mikkel JürgensDepartment of Endocrinology Rigshospitalet Copenhagen University Hospital Copenhagen Denmark.
Morten SchouDepartment of Cardiology Copenhagen University Hospitals Herlev/Gentofte Herlev Denmark.
Philip HasbakDepartment of Clinical Physiology Nuclear Medicine & PET and Cluster for Molecular Imaging Department of Biomedical Sciences Rigshospitalet and University of Copenhagen Copenhagen Denmark.
Andreas KjærDepartment of Clinical Physiology Nuclear Medicine & PET and Cluster for Molecular Imaging Department of Biomedical Sciences Rigshospitalet and University of Copenhagen Copenhagen Denmark.
Emil WolskDepartment of Cardiology The Heart CentreRigshospitalet Copenhagen University Hospital Copenhagen Denmark.
Bo ZerahnDepartment of Clinical Physiology and Nuclear Medicine Copenhagen University Hospitals Herlev/Gentofte Herlev Denmark.
Mikkel WibergDepartment of Endocrinology Rigshospitalet Copenhagen University Hospital Copenhagen Denmark.
Niels H Brandt-JacobsenDepartment of Endocrinology Rigshospitalet Copenhagen University Hospital Copenhagen Denmark.
Peter GædeSlagelse Hospital Slagelse Denmark.
Peter RossingDepartment of Clinical Medicine Faculty of Health and Medical Sciences University of Copenhagen Copenhagen Denmark.
Jens FaberDepartment of Endocrinology Copenhagen University HospitalHerlev/Gentofte Herlev Denmark.
Silvio E InzucchiYale Section of EndocrinologyYale University School of Medicine New Haven CT.
Finn GustafssonDepartment of Cardiology The Heart CentreRigshospitalet Copenhagen University Hospital Copenhagen Denmark.
Caroline KistorpDepartment of Endocrinology Rigshospitalet Copenhagen University Hospital Copenhagen Denmark.

Funding

Yale Diabetes Research CenterP30DK045735 · NIDDK · YALE UNIVERSITY · PI Kevan C Herold, GERALD I SHULMAN · 1993 to 2026
$44.0M
NIDDK NIH HHS P30 DK045735
6 · The paper itself

Abstract

Background Sodium-glucose cotransporter 2 inhibitors reduce hospitalizations for heart failure and cardiovascular death, although the underlying mechanisms have not been resolved. The SIMPLE trial (The Effects of Empagliflozin on Myocardial Flow Reserve in Patients With Type 2 Diabetes Mellitus) investigated the effects of empagliflozin on myocardial flow reserve (MFR) reflecting microvascular perfusion, in patients with type 2 diabetes mellitus at high cardiovascular disease risk. Methods and Results We randomized 90 patients to either empagliflozin 25 mg once daily or placebo for 13 weeks, as add-on to standard therapy. The primary outcome was change in MFR at week 13, quantified by Rubidium-82 positron emission tomography/computed tomography. The secondary key outcomes were changes in resting rate-pressure product adjusted MFR, changes to myocardial flow during rest and stress, and reversible cardiac ischemia. Mean baseline MFR was 2.21 (95% CI, 2.08-2.35). There was no change from baseline in MFR at week 13 in either the empagliflozin: 0.01 (95% CI, -0.18 to 0.21) or placebo groups: 0.06 (95% CI, -0.15 to 0.27), with no treatment effect -0.05 (95% CI, -0.33 to 0.23). No effects on the secondary outcome parameters by Rubidium-82 positron emission tomography/computed tomography was observed. Treatment with empagliflozin reduced hemoglobin A

Indexed as

Benzhydryl CompoundsDiabetes Mellitus, Type 2GlucosidesFemaleFractional Flow Reserve, MyocardialGlycated HemoglobinHeart Disease Risk FactorsHumansMaleMicrocirculationMiddle AgedMyocardial Perfusion ImagingNegative ResultsPositron Emission Tomography Computed TomographySodium-Glucose Transporter 2 InhibitorsBenzhydryl CompoundsempagliflozinGlucosidesGlycated HemoglobinSodium-Glucose Transporter 2 Inhibitorsempagliflozinmyocardial perfusionpositron emission tomographySGLT2 inhibitortype 2 diabetes mellitus

Identifiers

PMID34278803
PMCPMC8475664

What OpenQuestion holds

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Registered trials

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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.