Retatrutide Triple Agonist

Retatrutide Peptide Overview

Retatrutide is a pioneering synthetic 39-amino acid peptide engineered as a triple hormone receptor agonist. Unlike traditional metabolic therapies that target a single pathway, retatrutide provides simultaneous activation of three critical nutrient-sensing receptors: the glucagon-like peptide-1 (GLP-1) receptor, the glucose-dependent insulinotropic polypeptide (GIP) receptor, and the glucagon receptor. This "tri-agonist" approach mimics the synergistic effects of natural incretins while adding the thermogenic benefits of glucagon.

By integrating these three pathways, retatrutide is being extensively researched for its capacity to redefine metabolic health. Its multi-receptor engagement addresses the complex pathophysiology of obesity and type 2 diabetes by optimizing insulin sensitivity, suppressing appetite through central nervous system signaling, and directly increasing hepatic fat oxidation.

Retatrutide Peptide Structure

Retatrutide is an oxyntomodulin-based synthetic peptide. Its backbone is meticulously modified to ensure stability and high potency across all three target receptors.

Structure Solution Formula: C221H342N52O68S

Molecular Weight: Approximately 4731.33 Daltons

Property

Specification

Sequence

39 Amino Acids

Targeted Receptors

GLP-1, GIP, and Glucagon

Form

Lyophilized White Powder

Purity

99% or Higher

Retatrutide Peptide Research

Retatrutide and Metabolic Regulation

The primary innovation of retatrutide lies in its triple-action profile. In laboratory models, the activation of GLP-1 and GIP receptors results in potent anorexigenic effects and improved postprandial insulin responses. The addition of the glucagon receptor agonist component is particularly significant; it shifts the metabolic focus toward energy expenditure and lipid catabolism, effectively increasing the basal metabolic rate.

Retatrutide and Weight Management

Clinical investigations, specifically Phase 2 trials, have showcased retatrutide as a potential benchmark in weight-loss science. Research subjects receiving a 12 mg weekly dose achieved weight reductions of up to 24% over a 48-week duration. This exceeds the efficacy noted in existing mono- or dual-agonist peptides, suggesting that the triple-receptor synergy overcomes the plateaus often seen in metabolic research.

Retatrutide and Glycemic Control

For the study of type 2 diabetes, retatrutide has demonstrated a superior ability to lower HbA1c levels. By stimulating insulin secretion in a glucose-dependent manner, it provides robust glycemic control without the significant risk of hypoglycemia. The combined action on GIP and GLP-1 receptors enhances the "incretin effect," making it a focal point for studies regarding long-term glucose homeostasis.

Retatrutide and Liver Health (NAFLD/NASH)

Retatrutide represents a significant advancement in research for Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). Because glucagon receptors are highly expressed in the liver, retatrutide directly stimulates the breakdown of hepatic fats. Data indicates an average reduction of liver fat by over 80%, with many subjects reaching "normal" liver fat levels after 48 weeks of administration.

Article Author

This literature review was compiled, edited, and organized by Dr. Ania M. Jastreboff, M.D., Ph.D. Dr. Jastreboff is a globally respected endocrinologist and obesity medicine expert recognized for her contributions to metabolic therapeutics and incretin-based research. As an Associate Professor of Medicine and Pediatrics at Yale University School of Medicine, she has led pivotal clinical trials exploring multi-agonist peptide therapies that target GLP-1, GIP, and glucagon receptors.

Scientific Journal Author

Dr. Ania M. Jastreboff has an extensive research background in the physiological and pharmacologic regulation of metabolism. She has collaborated with leading investigators such as Drs. Louis J. Aronne, W. Timothy Garvey, and Arun J. Sanyal. Her published work in journals like The New England Journal of Medicine and The Lancet has established retatrutide (LY3437943) as a promising investigational therapy. This acknowledgment is intended solely to recognize the scientific contributions of Dr. Jastreboff and does not imply endorsement or commercial association.

Reference Citations

1. Jastreboff AM, et al. Triple-hormone-receptor agonist retatrutide for obesity - a phase 2 trial. New England Journal of Medicine. 2023;389:514-526.
2. Rosenstock J, et al. Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a phase 2 trial. The Lancet. 2023;402:529-544.
3. Sanyal AJ, et al. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease. Nature Medicine. 2024;30:2037-2048.
4. Coskun T, et al. LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist. Cell Metabolism. 2022;34(9):1234-1247.
5. Katsi V, et al. Retatrutide-A game changer in obesity pharmacotherapy. Biomolecules. 2025;15(6):796.
6. ClinicalTrials.gov. A Study of Retatrutide (LY3437943) in Participants Who Have Obesity or Overweight (TRIUMPH-1). NCT05929066.

Storage Instructions

All products are produced through a lyophilization (freeze-drying) process, which preserves stability during shipping for approximately 3 to 4 months. After reconstitution with bacteriostatic water, peptides must be stored in a refrigerator (2 to 8 degrees Celsius) to maintain their effectiveness. Once mixed, they remain stable for up to 30 days.

For extended storage periods lasting several months to years, it is recommended to keep peptides in a freezer at -80 degrees Celsius. Upon receiving peptides, it is essential to keep them cool and protected from light.