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What is Retatrutide? Retatrutide (LY3437943) is a synthetic peptide engineered as a once-weekly agonist of the GIP, GLP-1, and glucagon receptors. It consists of 39 amino acids conjugated to a C20 fatty diacid moiety, with preferential potency at the GIP receptor and extended half-life enabling weekly administration (Abouelmagd et al., 2025; Jastreboff et al., 2023). In controlled studies, retatrutide led to significant, dose-dependent reductions in body weight (up to −24.2%), BMI, and waist circumference over 48 weeks, alongside improvements in metabolic markers such as HbA1c, fasting glucose, and blood pressure. These effects are attributed to its multi-receptor mechanism enhancing energy expenditure, insulin secretion, and lipid metabolism (Abouelmagd et al., 2025). Pharmacologically, retatrutide’s multi-agonist activity is designed to exploit synergistic pathways in metabolic regulation. GIP agonism facilitates lipid handling and insulinotropic effects, GLP-1 activity supports glucose control and satiety signaling, and glucagon receptor activation increases hepatic fat oxidation (Abouelmagd et al., 2025; Jastreboff et al., 2023; Pasqualotto et al., 2024). Together, this receptor triad promotes coordinated modulation of energy balance and glycemic control.