Evidence mapPaperPMID 39809551Full record

SynthesisEuropean journal of heart failure2025

Unlocking the power of empagliflozin: Rescuing inflammation in hyperglycaemia-exposed human cardiomyocytes through comprehensive multi-level analysis.

Rosaria Benedetti, Ugo Chianese, Chiara Papulino, Lucia Scisciola, Mirko Cortese, Pietro Formisano, Nunzio Del Gaudio, Serena Cabaro, Vittoria D'Esposito, Ada Pesapane and 5 more

Abstract readMeta-Analysis
In one paragraph

Synthesis in European journal of heart failure, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
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

15 authors.

Rosaria Benedetti *Department of Precision Medicine, University of Campania 'Luigi Vanvitelli', Naples, Italy.
Ugo Chianese *Department of Precision Medicine, University of Campania 'Luigi Vanvitelli', Naples, Italy.ORCID https://orcid.org/0000-0003-2726-1895
Chiara PapulinoDepartment of Precision Medicine, University of Campania 'Luigi Vanvitelli', Naples, Italy.
Lucia ScisciolaDepartment of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy.
Mirko CorteseTelethon Institute of Genetics and Medicine, Pozzuoli, Italy.
Pietro FormisanoDepartment of Translational Medicine, University of Naples "Federico II", Naples, Italy.
Nunzio Del GaudioDepartment of Precision Medicine, University of Campania 'Luigi Vanvitelli', Naples, Italy.
Serena CabaroDepartment of Translational Medicine, University of Naples "Federico II", Naples, Italy.
Vittoria D'EspositoInstitute of Endocrinology and Oncology "Gaetano Salvatore" (IEOS), Naples, Italy.
Ada PesapaneDepartment of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy.
Mariarosaria ConteDepartment of Precision Medicine, University of Campania 'Luigi Vanvitelli', Naples, Italy.
Giuseppe SignorielloDepartment of Mental and Physical Health and Preventive Medicine, Section of Medical Statistics, University of Campania "Luigi Vanvitelli", Naples, Italy.
Michelangela BarbieriDepartment of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy.
Lucia AltucciDepartment of Precision Medicine, University of Campania 'Luigi Vanvitelli', Naples, Italy.
Giuseppe PaolissoDepartment of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy.

Funding

Ministero dell'Università e della Ricerca (MUR) e dal Ministero della Salute (Italian Government)National Plan for PNRR Complementary Investments
6 · The paper itself

Abstract

aimsHyperglycaemic conditions increase cardiac stress, a common phenomenon associated with inflammation, aging, and metabolic imbalance. Sodium-glucose cotransporter 2 inhibitors, a class of anti-diabetic drugs, showed to improve cardiovascular functions although their mechanism of action has not yet been fully established. This study investigated the effects of empagliflozin on cardiomyocytes following high glucose exposure, specifically focusing on inflammatory and metabolic responses. METHODS AND

resultsA three-part strategy was formulated: (i) a meta-analysis of selected randomized clinical trials was carried out to assess the anti-inflammatory effects of empagliflozin in diabetic patients; (ii) the impact of empagliflozin on human cardiomyocyte AC16 cells exposed to normal (5 mM) and high (33 mM) glucose concentrations for 2 and 7 days was explored by evaluating gene expression and protein levels of pivotal markers associated with cardiac inflammation, stress, endoplasmic reticulum damage, and calcium modulation; (iii) in silico data from bioinformatic analyses were exploited to construct an interaction map delineating the potential mechanism of action of empagliflozin on cardiac tissue. Empagliflozin reversed high-glucose mediated alterations at the transcriptional level, decreasing inflammatory, metabolic, and aging signatures. Specifically, in vitro experiments on human cardiomyocytes, meta-analyses of clinical data on inflammatory biomarkers from diabetic peripheral blood samples, and sequencing of pathological human heart tissues, all support that empagliflozin exerts anti-inflammatory effects both systemically and directly in cardiac tissue, on cardiomyocytes.

conclusionOur study provides insights based on robust mechanistic data for optimizing heart failure management and highlights the intricate interplay between diabetes, inflammation, aging, and cardiovascular health.

Indexed as

Benzhydryl CompoundsGlucosidesHyperglycemiaInflammationMyocytes, CardiacSodium-Glucose Transporter 2 InhibitorsHumansBenzhydryl CompoundsempagliflozinGlucosidesSodium-Glucose Transporter 2 InhibitorsEmpagliflozinGlucoseHuman cardiomyocytesInflammaging

Identifiers

PMID39809551
PMCPMC12103962

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.