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In the FIGHT [80] and LIVE [81] RCTs performed in patients with HF and reduced ejection fraction with and without T2DM, liraglutide treatment, compared to placebo, did not demonstrate a beneficial effect on left ventricular function, with a trend towards harm [80, 81]

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Another study found TMAO downregulates Piezo1, activating NOX4/ROS oxidative stress, causing abnormal calcium handling and fibrosis, constituting the molecular network of TMAO-induced cardiac fibrosis ( The above quadruple network links cardiac fibroblast proliferation, ER stress response, inflammatory signals and epigenetics, which together constitute the pathological basis of TMAO-induced fibrosis