What is Retatrutide?
Retatrutide (LY3437943) is a novel triple-receptor agonist that targets three incretin-related receptors simultaneously:
- GLP-1 (glucagon-like peptide-1) receptor
- GIP (glucose-dependent insulinotropic polypeptide) receptor
- Glucagon receptor
This triple mechanism represents the newest evolution in incretin-based research, building on the success of single (semaglutide) and dual (tirzepatide) receptor agonists. The addition of glucagon receptor activity may provide unique metabolic effects.
The 20mg vial is a high-capacity presentation. Reconstituted with 2mL of bacteriostatic water it holds a 10mg/mL concentration, which keeps injection volumes small — every dose up to 8mg fits inside a single U-100 syringe — while providing many doses per vial.
Quick Reference
| Parameter | Value |
|---|---|
| Peptide Amount | 20mg |
| Recommended BAC Water | 2mL |
| Resulting Concentration | 10mg/mL (10000mcg/mL) |
| Typical Research Dose | 1mg - 12mg weekly |
| Frequency | Once weekly |
| Research Duration | 24-48 weeks |
Reconstitution Guide
Materials Needed
- Retatrutide 20mg lyophilized vial
- Bacteriostatic water (BAC water)
- Insulin syringes (U-100, 29-31 gauge)
- Alcohol swabs
- Sharps container
Step-by-Step Instructions
-
Prepare workspace — Clean environment, gather materials, thorough handwashing.
-
Clean vial stoppers — Wipe both vials with alcohol swabs. Allow complete drying.
-
Draw BAC water — Draw 2mL bacteriostatic water using sterile syringe.
-
Add to peptide — Inject slowly along inside wall of vial. Never spray directly onto powder.
-
Dissolve — Allow 5-10 minutes for complete dissolution. Gentle swirl only — no shaking.
-
Verify — Solution must be completely clear and colorless.
-
Label and store — Note reconstitution date. Refrigerate immediately.
Dosage Protocol
Concentration Calculations
With 20mg peptide in 2mL BAC water:
- Concentration: 10mg/mL = 10000mcg/mL
- Per unit (U-100 syringe): 100mcg per unit
Common Dose Calculations
| Desired Dose | Draw Volume | Syringe Units |
|---|---|---|
| 1mg | 0.10mL | 10 units |
| 2mg | 0.20mL | 20 units |
| 4mg | 0.40mL | 40 units |
| 8mg | 0.80mL | 80 units |
| 12mg | 1.20mL | Split into 2 injections |
Suggested Titration Protocol
Based on phase 2 clinical trial design:
| Week | Dose | Notes |
|---|---|---|
| 1-4 | 1mg | Initial assessment |
| 5-8 | 2mg | First escalation |
| 9-12 | 4mg | Second escalation |
| 13-20 | 8mg | Third escalation |
| 21+ | 12mg | Maximum studied dose |
Important Notes:
- Each dose level maintained minimum 4 weeks
- Escalation based on tolerance
- Not all protocols require maximum dose
- Lower doses (4-8mg) may be sufficient for many research objectives
Injection Guide
Subcutaneous Administration
- Clean injection site with alcohol swab
- Pinch skin fold at chosen site
- Insert needle at 90° angle
- Inject slowly (large volumes over 10-15 seconds)
- Wait 10 seconds before withdrawing
- Do not massage site
Site Selection
Preferred sites:
- Abdomen (most common) — avoid 2 inches around navel
- Outer thigh
- Upper arm
Large Volume Injections
For doses at or above 12mg (>1mL):
- Consider splitting into 2 separate injections
- Use different sites for each injection
- Complete both injections within 15-minute window
Storage Requirements
Lyophilized (Powder)
- Temperature: -20°C (-4°F) or colder
- Duration: 2+ years
- Conditions: Dry, dark, protected from moisture
Reconstituted
- Temperature: 2-8°C (36-46°F)
- Duration: 4-6 weeks
- Conditions: Refrigerated, protected from light, never freeze
Research Considerations
Triple-Receptor Mechanism
Retatrutide’s unique mechanism targets:
GLP-1 Receptor:
- Appetite suppression
- Insulin secretion (glucose-dependent)
- Delayed gastric emptying
- Established metabolic effects
GIP Receptor:
- Enhanced insulin response
- Potential adipose tissue effects
- Complements GLP-1 activity
Glucagon Receptor:
- Increased energy expenditure
- Hepatic glucose output regulation
- Potential thermogenic effects
- May enhance weight reduction beyond dual agonists
Comparison to Other Incretins
| Peptide | GLP-1 | GIP | Glucagon | Max Weight Effect* |
|---|---|---|---|---|
| Semaglutide | ✓ | − | − | ~15-17% |
| Tirzepatide | ✓ | ✓ | − | ~20-22% |
| Retatrutide | ✓ | ✓ | ✓ | ~24% |
*Based on clinical trial data at maximum doses
Phase 2 Trial Highlights
Key findings from initial trials:
- Dose-dependent effects on body weight
- Effects observed across all dose groups
- Generally manageable tolerability profile
- Novel metabolic parameter changes
Safety Considerations
Research Precautions
- Retatrutide is an investigational compound
- Phase 3 trials ongoing
- Not approved for any indication in any jurisdiction
- Research use only — not for human consumption
- Limited long-term safety data available
Handling
- Use sterile technique for all preparations
- Never reuse needles or syringes
- Proper sharps disposal
- Store securely away from unauthorized access
Sourcing for Research
Source from verified suppliers that provide third-party testing and certificates of analysis (COA) for each batch. Compare purity documentation, shipping conditions, and batch traceability before purchasing research materials.
Scientific References
- Jastreboff AM, et al. “Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial.” N Engl J Med. 2023;389:514-526.
- Rosenstock J, et al. “Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial.” Lancet. 2023;402:529-544.
- Finan B, et al. “A rationally designed monomeric peptide triagonist corrects obesity and diabetes in rodents.” Nat Med. 2015;21:27-36.
Last updated: July 18, 2026
Disclaimer: This information is for educational and research purposes only. Retatrutide is an investigational compound in clinical development and is not approved for any use. Research-grade peptides are not intended for human consumption. Always follow applicable laws and institutional guidelines.