Retatrutide Triple Agonist

Retatrutide Peptide Overview

Retatrutide is an experimental, synthetic 39-amino acid peptide that functions as a powerful triple agonist. It is designed to target three distinct metabolic pathways by simultaneously activating the receptors for Glucagon-Like Peptide-1 (GLP-1), Glucose-Dependent Insulinotropic Polypeptide (GIP), and Glucagon. This multi-receptor approach is intended to provide a synergistic effect on metabolic regulation, surpassing the capabilities of traditional single-agonist or dual-agonist therapies. By modulating appetite, enhancing insulin secretion, and increasing energy expenditure, Retatrutide is a focal point for research into the treatment of chronic metabolic conditions such as obesity and type 2 diabetes.

Retatrutide Peptide Structure

The chemical composition of Retatrutide is optimized for high stability and receptor affinity. It is a modified peptide backbone derived from the gastric inhibitory polypeptide sequence.

Structure Solution Formula: C221H342N52O68S

Molecular Weight: 4731.33 Daltons

Parameter

Specification

Molecular Class

Triple Receptor Agonist

Sequence Length

39 Amino Acids

Target Receptors

GLP-1, GIP, Glucagon

Physical State

Lyophilized Powder

Retatrutide Peptide Research

Retatrutide and Metabolic Regulation

In preclinical models, Retatrutide has demonstrated a unique ability to coordinate metabolic functions across multiple organ systems. The activation of GLP-1 and GIP receptors primarily influences the pancreas and the central nervous system to regulate glucose and satiety. Meanwhile, the inclusion of the glucagon receptor agonist component targets the liver and adipose tissue, promoting the breakdown of fats and increasing the basal metabolic rate.

Retatrutide and Weight Management

Clinical data from Phase 2 trials indicate that Retatrutide produces substantial, dose-dependent weight loss. Researchers observed that participants reached a mean weight reduction of 24 percent over a 48-week period when administered the highest dose. This level of efficacy is significantly higher than that seen in previous generations of metabolic peptides, likely due to the "triple-threat" mechanism that prevents metabolic adaptation to caloric restriction.

Retatrutide and Glycemic Control

In studies focused on type 2 diabetes, Retatrutide shown a marked ability to lower HbA1c levels by up to 2.0 percent. Because the peptide stimulates insulin release specifically in response to elevated blood sugar, it offers a robust safety profile. Furthermore, the GIP component is believed to support the health of pancreatic beta cells, potentially offering long-term protective benefits for glycemic health.

Retatrutide and Liver Health (NAFLD/NASH)

Retatrutide is particularly noted for its impact on hepatic steatosis. Glucagon receptor activation in the liver promotes the oxidation of fatty acids, which has led to an 80 percent reduction in liver fat in clinical subjects. This makes Retatrutide a leading candidate for research into the reversal of non-alcoholic fatty liver disease (NAFLD) and metabolic-associated steatohepatitis (MASH).

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. 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.

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 Nature Medicine has established Retatrutide as a promising next-generation therapy. This acknowledgment is intended solely to recognize scientific contributions and does not imply endorsement.

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 randomized, double-blind, placebo-controlled, 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: a randomized phase 2a trial. Nature Medicine. 2024;30:2037-2048.
4. Coskun T, et al. LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist: from discovery to clinical proof of concept. 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/Program). NCT05929066.

Storage

All products are produced through a lyophilization process, which preserves stability during shipping for approximately 3 to 4 months. After reconstitution with bacteriostatic water, peptides must be stored in a refrigerator (at 4 degrees Celsius) to maintain effectiveness. Once mixed, they remain stable for up to 30 days. For long-term preservation, store in a freezer at -80 degrees Celsius to prevent degradation.