SynthesisCardiovascular diabetology2024

Evidence that tirzepatide protects against diabetes-related cardiac damages.

Fatemeh Taktaz, Lucia Scisciola, Rosaria Anna Fontanella, Ada Pesapane, Puja Ghosh, Martina Franzese, Giovanni Tortorella, Armando Puocci, Eduardo Sommella, Giuseppe Signoriello and 3 more

Open access · goldAbstract readMeta-Analysis
In one paragraph

Synthesis in Cardiovascular diabetology, 2024. The graph read 1 number from its abstract, feeding 1 cell of the map, but none could be read as for or against, so it casts no vote. Cited by 25 papers, 1 of them a synthesis that pooled it.

1number the graph read from it
0cells of the map it votes in
25citing papers in PubMed, 1 pooled it
13.2field-weighted citation impact, top 1% 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.

Read, but not usablea number the graph found but could not read as for or against

Cardiovascular eventscomparator not stated · t2d, liverfeeds one cell of the map
HR 0.590.40 to 0.79
RESULTS: Meta-analysis showed a reduced risk for MACE events by TZT therapy (HR was 0.59 (95% CI 0.40-0.79, Heterogeneity: r CONCLUSION: Our findings indicate that TZT has beneficial effects on cardiac cells by positively modulating cardiomyocyte death, fibrosis, and hypertrophy in the presence of high glucose concentrations.

clause the extractor read what became the number

2 · Its place on the map

Where it lands on the map

Rows are treatments, columns are outcomes. The coloured squares are the cells this paper feeds, coloured by the vote it casts there. Click one to jump to what this paper adds to it.

supports the treatmentfavours the comparatorno clear differenceread, but no usable result
3 · What it changes

What it adds to each cell

For every cell the paper feeds: the belief in the claim with and without this paper, and this paper's estimate drawn against every other readable study in the cell. The ringed dot is this paper.

GIP/GLP-1 & amylin agonists×cardiovascular events

No readable resultOpen on the map →What to test next →

2 readable studies in this cell: 2 favour the treatment, 0 find no difference, 0 favour the comparator.

Belief with this paper
0.50one trial · 1 family supports, 0 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
1 · no effect
NCT04847557731 enrolled · 2021
HR 0.620.41 to 0.95
NCT05564039282 enrolled · 2022
OR 20.48.40 to 49.8

This paper's own estimate is on a different scale from the rest of the cell, so it is not drawn here.

4 · 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.

5 · Its place in the literature

Who cites it

25 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.

  1. Effect of Tirzepatide on arrhythmic, major cardiovascular, and neurological outcomes in patients with type 2 diabetes: A systematic review and meta-analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025 · on this map
    Pooled it
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  10. Target Trial Emulations of GLP-1 and Dual GLP-1/GIP Agonists to Reduce Major Adverse Liver Outcomes in Type 2 Diabetes.Liver international : official journal of the International Association for the Study of the Liver · 2025
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6 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

7 · Who and what money

Authors and funding

13 authors at 4 institutions in 1 country.

Fatemeh Taktaz *Department of Advanced Medical and Surgical Sciences, University of Campania ''Luigi Vanvitelli'', P.zza L. Miraglia, 2, 80138, Naples, Italy.
Lucia Scisciola *Department of Advanced Medical and Surgical Sciences, University of Campania ''Luigi Vanvitelli'', P.zza L. Miraglia, 2, 80138, Naples, Italy. lucia.scisciola@unicampania.it.
Rosaria Anna FontanellaDepartment of Advanced Medical and Surgical Sciences, University of Campania ''Luigi Vanvitelli'', P.zza L. Miraglia, 2, 80138, Naples, Italy.
Ada PesapaneDepartment of Advanced Medical and Surgical Sciences, University of Campania ''Luigi Vanvitelli'', P.zza L. Miraglia, 2, 80138, Naples, Italy.
Puja GhoshDepartment of Advanced Medical and Surgical Sciences, University of Campania ''Luigi Vanvitelli'', P.zza L. Miraglia, 2, 80138, Naples, Italy.
Martina FranzeseDepartment of Advanced Medical and Surgical Sciences, University of Campania ''Luigi Vanvitelli'', P.zza L. Miraglia, 2, 80138, Naples, Italy.
Giovanni TortorellaDepartment of Advanced Medical and Surgical Sciences, University of Campania ''Luigi Vanvitelli'', P.zza L. Miraglia, 2, 80138, Naples, Italy.
Armando PuocciDepartment of Advanced Medical and Surgical Sciences, University of Campania ''Luigi Vanvitelli'', P.zza L. Miraglia, 2, 80138, Naples, Italy.
Eduardo SommellaDepartment of Pharmacy, University of Salerno, Fisciano, SA, Italy.
Giuseppe SignorielloDepartment of Mental Health and Public Medicine, Section of Statistic, University of Campania, Naples, Italy.
Fabiola OlivieriDepartment of Clinical and Molecular Sciences, DISCLIMO, Università Politecnica delle Marche, Ancona, Italy.
Michelangela Barbieri *Department of Advanced Medical and Surgical Sciences, University of Campania ''Luigi Vanvitelli'', P.zza L. Miraglia, 2, 80138, Naples, Italy.
Giuseppe Paolisso *Department of Advanced Medical and Surgical Sciences, University of Campania ''Luigi Vanvitelli'', P.zza L. Miraglia, 2, 80138, Naples, Italy.
University of Campania "Luigi Vanvitelli" · ITInnova (Italy) · ITSaint Camillus International University of Health and Medical Sciences · ITUniversity of Salerno · IT

Funding

AdvaNced Technologies for Human-centrEd Medicine (project acronym: ANTHEM PNC0000003PRIN: PROGETTI DI RICERCA DI RILEVANTE INTERESSE NAZIONALE / Bando 2022 2022CX7HTJPROGETTI DI RICERCA DI RILEVANTE INTERESSE NAZIONALE - Bando 2020 2020N5WK98
8 · The paper itself

Abstract

The marked sentences are the ones the graph read a number from.

backgroundGlucagon-like peptide-1 receptor agonists (GLP-1RAs) are effective antidiabetic drugs with potential cardiovascular benefits. Despite their well-established role in reducing the risk of major adverse cardiovascular events (MACE), their impact on heart failure (HF) remains unclear. Therefore, our study examined the cardioprotective effects of tirzepatide (TZT), a novel glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) receptor agonist.

methodsA three-steps approach was designed: (i) Meta-analysis investigation with the primary objective of assessing major adverse cardiovascular events (MACE) occurrence from major randomized clinical trials.; (ii) TZT effects on a human cardiac AC16 cell line exposed to normal (5 mM) and high (33 mM) glucose concentrations for 7 days. The gene expression and protein levels of primary markers related to cardiac fibrosis, hypertrophy, and calcium modulation were evaluated. (iii) In silico data from bioinformatic analyses for generating an interaction map that delineates the potential mechanism of action of TZT.

resultsMeta-analysis showed a reduced risk for MACE events by TZT therapy (HR was 0.59 (95% CI 0.40-0.79, Heterogeneity: r

conclusionOur findings indicate that TZT has beneficial effects on cardiac cells by positively modulating cardiomyocyte death, fibrosis, and hypertrophy in the presence of high glucose concentrations. This suggests that TZT may reduce the risk of diabetes-related cardiac damage, highlighting its potential as a therapeutic option for heart failure management clinical trials. Our study strongly supports the rationale behind the clinical trials currently underway, the results of which will be further investigated to gain insights into the cardiovascular safety and efficacy of TZT.

Indexed as

Diabetes MellitusDiabetes Mellitus, Type 2Gastric Inhibitory PolypeptideGlucagon-Like Peptide-2 ReceptorHeart FailureFibrosisGlucagon-Like Peptide-1 ReceptorGlucoseHumansHypertrophyHypoglycemic AgentsMyocytes, CardiacTirzepatideGastric Inhibitory PolypeptideGlucagon-Like Peptide-1 ReceptorGlucagon-Like Peptide-2 ReceptorGlucoseHypoglycemic AgentsTirzepatideAC16 cell lineGIP receptorGLP-1 receptor.Heart failureHigh glucoseTirzepatide

Identifiers

PMID38555463
PMCPMC10981817
OpenAlexW4393338099

What OpenQuestion holds

Texttitle and abstract
LicenceCC BY
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 OpenQuestion graph.