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Tirzepatides imbalanced receptor engagement, which favors GIP receptor activation, combined with biased signaling at the GLP-1 receptor, further enhances insulin secretion and metabolic benefits ( 3.2.2 Regulation of hepatic lipid metabolism Dual GLP-1 receptor agonists facilitate hepatic lipid metabolism through coordinated activation of intracellular signaling pathways that suppress lipogenesis and enhance fatty acid oxidation

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Biological chemistry , 390 (3), 191-214

Specifically, retatrutide simultaneously activates three incretin and metabolic hormone receptors: GLP-1 (glucagon-like peptide-1) receptor which reduces appetite and slows gastric emptying [6] [7] GIP (glucose-dependent insulinotropic polypeptide) receptor which enhances insulin secretion and may improve fat metabolism [9] [10] Glucagon receptor which may increase energy expenditure and, based on early clinical and preclinical data, could promote hepatic fat metabolism This triple-action mechanism sets retatrutide apart from existing approved therapies such as semaglutide (a GLP-1 agonist) or tirzepatide (a dual GLP-1/GIP agonist)