Evidence that tirzepatide protects against diabetes-related cardiac damages

Autor: Fatemeh Taktaz, Lucia Scisciola, Rosaria Anna Fontanella, Ada Pesapane, Puja Ghosh, Martina Franzese, Giovanni Tortorella, Armando Puocci, Eduardo Sommella, Giuseppe Signoriello, Fabiola Olivieri, Michelangela Barbieri, Giuseppe Paolisso
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Cardiovascular Diabetology, Vol 23, Iss 1, Pp 1-15 (2024)
Druh dokumentu: article
ISSN: 1475-2840
DOI: 10.1186/s12933-024-02203-4
Popis: Abstract Background Glucagon-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. Methods A 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. Results Meta-analysis showed a reduced risk for MACE events by TZT therapy (HR was 0.59 (95% CI 0.40–0.79, Heterogeneity: r2 = 0.01, I2 = 23.45%, H2 = 1.31). In the human AC16 cardiac cell line treatment with 100 nM TZT contrasted high glucose (HG) levels increase in the expression of markers associated with fibrosis, hypertrophy, and cell death (p
Databáze: Directory of Open Access Journals
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