What is Retatrutide?
Retatrutide is a triple agonist of GIP, GLP-1, and glucagon receptors—making it the first "triple G" agonist in development. Developed by Eli Lilly, retatrutide has shown unprecedented weight loss results in Phase 2 trials, exceeding even tirzepatide.
By activating three metabolic hormone receptors simultaneously, retatrutide represents the next evolution beyond dual agonists like tirzepatide.
Mechanism of Action
Triple Receptor Activation
GLP-1 Receptor:
- Appetite reduction
- Glucose-dependent insulin secretion
- Delayed gastric emptying
GIP Receptor:
- Enhanced insulin secretion
- Metabolic effects
- May improve tolerability
Glucagon Receptor:
- Increased energy expenditure
- Hepatic glucose regulation
- Additional weight loss mechanism
Clinical Trial Results
Phase 2 (Published 2023)
Record-breaking weight loss:
| Dose | Weight Loss at 48 weeks |
|---|---|
| 1 mg | ~8% |
| 4 mg | ~17% |
| 8 mg | ~22% |
| 12 mg | ~24.2% |
This exceeds results from:
- Semaglutide (~15-17%)
- Tirzepatide (~22%)
Development Status
- Phase 3 trials ongoing
- Studying obesity and diabetes
- Potential approval: 2026-2027
- Eli Lilly development
Side Effects (Phase 2)
Common:
- Nausea
- Diarrhea
- Vomiting
- Constipation
Similar to other incretin agonists, with dose-dependent GI effects.
Comparison
| Agonist | Receptors | Weight Loss |
|---|---|---|
| Semaglutide | GLP-1 | ~15-17% |
| Tirzepatide | GIP + GLP-1 | ~22% |
| Retatrutide | GIP + GLP-1 + Glucagon | ~24% |
Summary
Retatrutide represents the cutting edge of metabolic peptide therapy, with triple agonism producing the highest weight loss results seen in clinical trials.
Key Points:
- Classification: Triple agonist (GIP/GLP-1/Glucagon)
- Developer: Eli Lilly
- Status: Phase 3 trials
- Weight Loss: Up to 24% in Phase 2