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These effects were subsequently managed through slower absorption kinetics, extended dosing intervals, and careful titration, allowing therapeutic benefit to outweigh adverse events ( 5.1 Peptide YY and the misinterpretation of early tolerability signals Peptide YY (PYY) is secreted postprandially by enteroendocrine L cells and functions as a satiety hormone by activating Y2 receptors in the hypothalamus and brainstem, where it inhibits neuropeptide Ymediated orexigenic signaling ( However, subsequent clinical trials reported high rates of nausea and vomiting, leading to the perception that PYY-based therapies were intrinsically intolerable