Retatrutide
Investigational triple agonist of GLP-1, GIP, and glucagon receptors.
Also known as: LY3437943, GGG tri-agonist
Retatrutide is an experimental peptide engineered to activate three metabolic receptors in a single molecule. It remains in clinical development and is not approved by any regulatory agency for human use, but early trial data have drawn significant attention in the metabolic research community.
Key facts
- Class
- GLP-1 / GIP / glucagon receptor triple agonist
- Originator
- Eli Lilly (development code LY3437943)
- Regulatory status
- Investigational; not approved for any use
- Development phase
- Phase 3 trials in progress as of late 2024
- Administration in trials
- Once-weekly subcutaneous injection
What is retatrutide?
Retatrutide is a synthetic peptide developed by Eli Lilly under the code LY3437943. It is sometimes referred to informally as a GGG tri-agonist because it acts at the glucagon receptor in addition to the GLP-1 and GIP receptors that GLP-1 and dual agonists target.
The molecule is in active clinical development and has not been approved by the FDA, EMA, or any other regulatory authority. Any material sold outside of formal clinical trials is intended for laboratory research only.
Mechanism of action
Retatrutide activates three receptors that all play roles in energy balance. GLP-1 and GIP receptor signaling contribute to insulin secretion and appetite suppression, as they do for tirzepatide. The novel feature is added glucagon receptor activity, which researchers propose may increase energy expenditure and influence hepatic lipid metabolism.
- •GLP-1 receptor activation reduces appetite and supports glucose-dependent insulin secretion
- •GIP receptor activation contributes to insulin response and may affect adipose tissue
- •Glucagon receptor activation may increase resting energy expenditure and promote hepatic fat oxidation
- •The balance of activity at each receptor is tuned during drug design to reach a specific pharmacological profile
Clinical trial history
A phase 2 trial in adults with obesity was published in the New England Journal of Medicine in 2023. At 48 weeks, participants receiving the highest retatrutide dose tested experienced an average body weight reduction of approximately 24 percent, compared with about 2 percent in the placebo arm. A separate phase 2 study in adults with type 2 diabetes was also published in 2023.
The TRIUMPH program comprises several phase 3 trials evaluating retatrutide in obesity, obesity with knee osteoarthritis, obesity with cardiovascular disease, and other populations. These trials were still in progress as of late 2024, and regulatory decisions have not been made.
Safety and regulatory context
Gastrointestinal effects, including nausea, vomiting, and diarrhea, were the most commonly reported adverse events in retatrutide phase 2 trials and tended to occur during dose escalation. Investigators have also monitored for heart rate increases, which were reported in a dose-related pattern in some studies.
Because retatrutide is investigational, there is no approved prescribing information and no established real-world safety database. Material marketed as research retatrutide is not cleared for human use and should be treated as a laboratory reagent only.
Research sourcing
Retatrutide is listed by our research partner, GLP1 Research Lab, which supplies lyophilized peptides for laboratory use. Listings include product identifiers relevant to research documentation.
View Retatrutide listing at GLP1 Research LabAffiliate partnership. Metabolic Playbook may earn a commission on purchases made through this link at no additional cost to the researcher.