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doi: 10.3390/ijms24054822

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At the cellular level, GLP-1 agonists exert several beneficial effects: Cardiomyocyte protection : GLP-1 agonists inhibit receptor-interacting protein kinase 3/mixed lineage kinase domain-like pseudokinase-mediated myocardial necroptosis by activating the GLP-1R/PI3K/Akt pathway [5] Anti-fibrotic effects : These agents alleviate cardiac fibrosis and hypertrophy by upregulating atrial natriuretic peptide expression, which suppresses the calcineurin/nuclear factor of activated T cells 3 signaling pathway [5] Cellular stress reduction : GLP-1 agonists diminish endoplasmic reticulum stress and enhance autophagy in cardiomyocytes, preventing apoptosis and blocking progression to heart failure [5] Vascular effects : In vascular smooth muscle cells, GLP-1R activation primarily leads to Gs-mediated cAMP/PKA signaling while simultaneously inhibiting pro-proliferative pathways including ERK1/2 and p38 MAPK [4] Beyond these direct cellular effects, GLP-1 agonists improve cardiac function through multiple systemic mechanisms

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Among patients with T2D, semaglutide and tirzepatide result in placebo-adjusted 6.2% and 11.6% average total body weight reduction at one year

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