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When adverse effects mirror the peptides known physiological actions rather than off-target toxicity, the appropriate response may be signal bias or contextual restriction rather than target rejection

Retatrutide is a synthetic peptide that functions as a triple receptor agonist: GLP-1 Receptor : Glucagon-like peptide-1 (appetite suppression, glucose control) GIP Receptor : Glucose-dependent insulinotropic polypeptide (synergistic metabolic effects) Glucagon Receptor : Direct activation of thermogenesis and fat oxidation This triple mechanism is why retatrutide outperforms single and dual agonists in clinical trials

Clinical Practice in Rheumatology , 40(2), 234-245