What is Retatrutide?
Retatrutide (LY3437943) is an investigational triple hormone receptor agonist developed by Eli Lilly. Unlike GLP-1 monotherapy agents such as semaglutide, retatrutide simultaneously targets three key metabolic receptors: GLP-1 (glucagon-like peptide-1), GIP (glucose-dependent insulinotropic polypeptide), and the glucagon receptor.
While semaglutide targets GLP-1 alone and tirzepatide targets GLP-1 plus GIP, the addition of glucagon receptor agonism in retatrutide creates a more powerful metabolic effect. Glucagon receptor activation increases energy expenditure and promotes fat burning in the liver, working synergistically with the appetite suppression of GLP-1 and the insulin sensitization of GIP.
In Phase 2 clinical trials (TRYBE-1), retatrutide demonstrated unprecedented weight loss results. Participants receiving the highest dose (12 mg weekly) achieved an average body weight reduction of approximately 24% over 48 weeks. This surpasses outcomes seen with semaglutide (approximately 15%) and tirzepatide (approximately 21%) in comparable trial populations.
Retatrutide is currently in Phase 3 clinical trials. It is not FDA-approved and remains an investigational compound. All research-use information on this page is derived from peer-reviewed clinical trial publications and pre-clinical data.
Research Supply
Source high-purity Retatrutide for your research
Dosage Guide
Route: Subcutaneous injection, once weekly
Dosing Schedule
| Period | Dose |
|---|---|
| Weeks 1-4 | 2 mg |
| Weeks 5-8 | 4 mg |
| Weeks 9-12 | 8 mg |
| Week 13+ | 12 mg (highest studied dose) |
Reconstitution
Injection Volumes
| Dose | Volume | Syringe Units |
|---|---|---|
| 2 mg | 0.4 mL | 40 units |
| 4 mg | 0.8 mL | 80 units |
| 8 mg | 1.6 mL | Use two injections of 0.8 mL |
| 12 mg | 2.4 mL | Use two injections of 1.2 mL |
Administration Tips
- Inject subcutaneously in the abdomen, thigh, or upper arm
- Rotate injection sites weekly to avoid lipohypertrophy
- Administer on the same day each week for consistent plasma levels
- Store reconstituted solution refrigerated (2-8C) and use within 28 days
- Allow solution to reach room temperature before injecting to reduce discomfort
- Use a 29-31 gauge, 4-8mm pen needle or insulin syringe
Risks & Side Effects
Commonly Reported
Serious Risks
Pancreatitis
Risk of pancreatic inflammation, as with other incretin-based therapies. Discontinue immediately if severe abdominal pain develops.
Gallbladder disease
Rapid weight loss may increase the risk of gallstone formation. Biliary colic and cholecystitis have been reported with GLP-1 class agents.
Hypoglycemia
Particularly when combined with other glucose-lowering agents such as sulfonylureas or insulin. Monitor blood glucose carefully.
Hepatotoxicity
Glucagon receptor activation may affect liver function; monitoring of liver enzymes is recommended during use.
Increased heart rate
Dose-dependent increases in resting heart rate were observed in Phase 2 trials at higher doses, consistent with other GLP-1 receptor agonists.
Thyroid C-cell tumors
A theoretical risk based on GLP-1 receptor agonist class warnings from rodent studies. Clinical significance in humans remains under investigation.
Contraindications
- Personal or family history of medullary thyroid carcinoma
- Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
- Severe hepatic impairment
- Pregnancy or breastfeeding
- Known hypersensitivity to retatrutide or any excipient
- Active or history of pancreatitis
Frequently Asked Questions
Related Peptides
Experts Covering Retatrutide
Dr. William A. Seeds
MD -- Regenerative Medicine Pioneer
Dr. Andrew Huberman
PhD -- Stanford Neuroscientist
Jay Campbell
Health Optimization Author and Peptide Advocate
Dr. Ian W. Hamley
Diamond Professor of Physical Chemistry -- University of Reading
Matthew Farrahi
Biohacker, CEO of Sigma Compounds, and Fitness Creator
LEGAL DISCLAIMER
The information provided on this page is for educational and informational purposes only and is not intended as medical advice. Retatrutide is an investigational compound that has not been approved by the FDA or any regulatory authority. Always consult with a qualified healthcare professional before starting any peptide therapy. Individual results may vary. Peptides Institute is not responsible for any adverse effects resulting from the use of information provided on this site.