Evidence map›Paper›PMID 25402275›Full record

ArticlePloS one2014

The sodium-glucose co-transporter 2 inhibitor empagliflozin improves diabetes-induced vascular dysfunction in the streptozotocin diabetes rat model by interfering with oxidative stress and glucotoxicity.

Matthias Oelze, Swenja Kröller-Schön, Philipp Welschof, Thomas Jansen, Michael Hausding, Yuliya Mikhed, Paul Stamm, Michael Mader, Elena Zinßius, Saule Agdauletova and 7 more

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03151343 (Effects of SGLT-2 Inhibitor on Myocardial Perfusion, Function and Metabolism in Type 2 DM Patients at High Cardiovascular Risk), which is not on this map. Cited by 150 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
150citing papers in PubMed, 4 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.

NCT03151343 phase3completedstarted 2017, after this paper: background citation

Effects of SGLT-2 Inhibitor on Myocardial Perfusion, Function and Metabolism in Type 2 DM Patients at High Cardiovascular Risk: The SIMPle Randomized Clinical Trial

Ran2017Enrolled92Registered outcomes22Posted comparisons0ConditionsType2 Diabetes MellitusArmsempagliflozin, Placebo Oral Tablet
PMID 24948511PMID 24463454PMID 24176441PMID 15522914PMID 17556173PMID 18023248PMID 22753861PMID 23137505PMID 23219297PMID 23524053PMID 24449227PMID 25344694other papers from this trial
Open the trial in the graph
3 · Its place in the literature

Who cites it

150 citing papers in PubMed, 4 syntheses or guidelines pooled it, 289 citations in OpenAlex.

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  20. Diabetic neuropathy: cutting-edge research and future directions.Signal transduction and targeted therapy · 2025
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90 more citing papers are in PubMed but not listed here.

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

17 authors at 4 institutions in 2 countries.

Matthias Oelze2nd Medical Clinic, Department of Cardiology, Medical Center of the Johannes Gutenberg University, Mainz, Germany.
Swenja Kröller-Schön2nd Medical Clinic, Department of Cardiology, Medical Center of the Johannes Gutenberg University, Mainz, Germany.
Philipp Welschof2nd Medical Clinic, Department of Cardiology, Medical Center of the Johannes Gutenberg University, Mainz, Germany.
Thomas Jansen2nd Medical Clinic, Department of Cardiology, Medical Center of the Johannes Gutenberg University, Mainz, Germany.
Michael Hausding2nd Medical Clinic, Department of Cardiology, Medical Center of the Johannes Gutenberg University, Mainz, Germany.
Yuliya Mikhed2nd Medical Clinic, Department of Cardiology, Medical Center of the Johannes Gutenberg University, Mainz, Germany.
Paul Stamm2nd Medical Clinic, Department of Cardiology, Medical Center of the Johannes Gutenberg University, Mainz, Germany.
Michael Mader2nd Medical Clinic, Department of Cardiology, Medical Center of the Johannes Gutenberg University, Mainz, Germany.
Elena Zinßius2nd Medical Clinic, Department of Cardiology, Medical Center of the Johannes Gutenberg University, Mainz, Germany.
Saule Agdauletova2nd Medical Clinic, Department of Cardiology, Medical Center of the Johannes Gutenberg University, Mainz, Germany.
Anna Gottschlich2nd Medical Clinic, Department of Cardiology, Medical Center of the Johannes Gutenberg University, Mainz, Germany.
Sebastian Steven2nd Medical Clinic, Department of Cardiology, Medical Center of the Johannes Gutenberg University, Mainz, Germany.
Eberhard Schulz2nd Medical Clinic, Department of Cardiology, Medical Center of the Johannes Gutenberg University, Mainz, Germany.
Serge P BottariLaboratory of Fundamental and Applied, Bioenergetics, INSERM U1055, Grenoble-Alpes Université et Pôle de Biologie, CHU, Grenoble, France.
Eric MayouxBoehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.
Thomas Münzel2nd Medical Clinic, Department of Cardiology, Medical Center of the Johannes Gutenberg University, Mainz, Germany.
Andreas Daiber2nd Medical Clinic, Department of Cardiology, Medical Center of the Johannes Gutenberg University, Mainz, Germany.
University Medical Center of the Johannes Gutenberg University Mainz · DEJohannes Gutenberg University Mainz · DEBoehringer Ingelheim (Germany) · DELaboratory of Fundamental and Applied Bioenergetics · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveIn diabetes, vascular dysfunction is characterized by impaired endothelial function due to increased oxidative stress. Empagliflozin, as a selective sodium-glucose co-transporter 2 inhibitor (SGLT2i), offers a novel approach for the treatment of type 2 diabetes by enhancing urinary glucose excretion. The aim of the present study was to test whether treatment with empagliflozin improves endothelial dysfunction in type I diabetic rats via reduction of glucotoxicity and associated vascular oxidative stress.

methodsType I diabetes in Wistar rats was induced by an intravenous injection of streptozotocin (60 mg/kg). One week after injection empagliflozin (10 and 30 mg/kg/d) was administered via drinking water for 7 weeks. Vascular function was assessed by isometric tension recording, oxidative stress parameters by chemiluminescence and fluorescence techniques, protein expression by Western blot, mRNA expression by RT-PCR, and islet function by insulin ELISA in serum and immunohistochemical staining of pancreatic tissue. Advanced glycation end products (AGE) signaling was assessed by dot blot analysis and mRNA expression of the AGE-receptor (RAGE).

resultsTreatment with empagliflozin reduced blood glucose levels, normalized endothelial function (aortic rings) and reduced oxidative stress in aortic vessels (dihydroethidium staining) and in blood (phorbol ester/zymosan A-stimulated chemiluminescence) of diabetic rats. Additionally, the pro-inflammatory phenotype and glucotoxicity (AGE/RAGE signaling) in diabetic animals was reversed by SGLT2i therapy.

conclusionsEmpagliflozin improves hyperglycemia and prevents the development of endothelial dysfunction, reduces oxidative stress and improves the metabolic situation in type 1 diabetic rats. These preclinical observations illustrate the therapeutic potential of this new class of antidiabetic drugs.

Indexed as

Diabetes Mellitus, ExperimentalSodium-Glucose Transporter 2 InhibitorsAnimalsBenzhydryl CompoundsBlood GlucoseCytokinesDiabetes ComplicationsDiabetic AngiopathiesGene ExpressionGlucoseGlucosidesHemodynamicsInflammation MediatorsInsulinMaleOxidative StressBenzhydryl CompoundsBlood GlucoseCytokinesempagliflozinGlucoseGlucosidesInflammation MediatorsInsulinReceptor for Advanced Glycation End ProductsReceptors, ImmunologicRNA, MessengerSodium-Glucose Transporter 2 InhibitorsStreptozocin

Identifiers

PMID25402275
PMCPMC4234367
OpenAlexW2083485319

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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.