Retatrutide

Retatrutide is an investigational peptide designed to activate three receptors: GIP, GLP-1, and glucagon receptors. Because these receptors participate in overlapping but distinct aspects of metabolic regulation, retatrutide is studied as a model for multi-receptor incretin and glucagon biology. Research focuses on body-weight physiology, glucose metabolism, appetite signaling, energy expenditure, hepatic fat metabolism, and cardiometabolic biomarkers.

Retatrutide combines incretin-receptor signaling with glucagon-receptor activity. GLP-1 and GIP signaling are associated with insulin response and appetite-regulation pathways, while glucagon-receptor signaling is tied to hepatic glucose output, lipid metabolism, and energy expenditure. Triple agonism is researched to understand how these pathways interact when activated together and whether coordinated receptor activity creates a distinct metabolic profile.

• Multi-receptor incretin biology and receptor-selectivity questions.
• Energy expenditure, appetite signaling, and weight-regulation physiology.
• Liver-related metabolic endpoints, including hepatic fat and lipid handling.
• Glucose regulation, insulin sensitivity markers, and postprandial metabolic response.
• Long-term cardiometabolic biomarker changes in controlled research settings.

• Jastreboff AM et al. Triple-hormone-receptor agonist retatrutide for obesity — a phase 2 trial. New England Journal of Medicine, 2023.
• Coskun T et al. LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist. Cell Metabolism, 2022.
• Tschöp MH et al. Unimolecular polypharmacy for treatment of diabetes and obesity. Cell Metabolism, 2016.