Description

Retatrutide (Triple GIP/GLP-1/Glucagon Receptor Agonist)

Retatrutide is a novel, synthetic triagonist peptide designed to simultaneously target three key metabolic hormone receptors: GIP (glucose-dependent insulinotropic polypeptide), GLP-1 (glucagon-like peptide-1), and glucagon receptors. This unique receptor profile positions Retatrutide as a potent investigational compound in the study of energy homeostasis, glucose regulation, and body composition remodeling.

In preclinical and early clinical models, Retatrutide has demonstrated superior metabolic activity compared to dual agonists by leveraging synergistic signaling pathways to regulate appetite, increase insulin sensitivity, promote lipolysis, and enhance energy expenditure. This makes it a high-value target for research into obesity, insulin resistance, and metabolic syndrome.

Chemical Makeup

• Molecular Formula: C213H327N55O63

• Molecular Weight: ~4747.4 g/mol

• Form: Lyophilized powder (for reconstitution)

• Solubility: Water-soluble

• Structure: Synthetic linear peptide with fatty acid side-chain for prolonged half-life

• Half-Life (in vivo models): Estimated 6–8 days

Research & Preclinical Investigations

Triple Receptor Activation

Retatrutide’s design allows it to activate GIPR, GLP-1R, and GCGR in a balanced ratio, mimicking the effect of multiple incretin and energy-regulating hormones. Animal models indicate this triagonist mechanism may result in enhanced insulin secretion, appetite suppression, glucose clearance, and increased resting energy expenditure, exceeding the effects observed in dual agonists such as Tirzepatide.

Weight and Fat Mass Reduction

In rodent models of obesity and metabolic syndrome, Retatrutide administration has shown rapid and sustained reductions in body weight, attributed to both adipose tissue catabolism and reduced food intake. These effects are believed to be mediated through central hypothalamic appetite centers and peripheral lipolytic signals.

Glycemic Control

Studies in diabetic animal models show that Retatrutide may significantly lower fasting glucose, HbA1c, and insulin resistance markers. The compound improves both first- and second-phase insulin response while reducing hepatic glucose output via glucagon receptor modulation.

Liver Health and Lipid Metabolism

Preclinical data suggest that Retatrutide may reduce hepatic steatosis by promoting fatty acid oxidation and reducing de novo lipogenesis. These findings have prompted ongoing investigations into its role in non-alcoholic fatty liver disease (NAFLD) and metabolic-associated steatohepatitis (MASH).

Research Use Only

Retatrutide is provided strictly for in vitro and in vivo laboratory research purposes. It is not approved for human use, therapeutic applications, or diagnostic procedures. All research must follow institutional safety and handling protocols.

References

1. Coskun T, Sloop KW, et al. Triple GIP, GLP-1, and glucagon receptor agonist retatrutide improves obesity and metabolic dysfunction in rodents and primates. Sci Transl Med. 2023;15(697):eabo0049.

2. He H, Tran T, et al. Retatrutide induces superior weight loss and glycemic control in preclinical models compared to dual agonists. Cell Metab. 2023;35(1):55–69.

3. Jastreboff AM, et al. Retatrutide as a triple hormone receptor agonist for obesity: Phase 1 findings. N Engl J Med. 2023;388(3):203–216.