Retatrutide
Also known as: LY3437943 · Triple agonist GLP-1/GIP/Glucagon · Eli Lilly LY3437943
Retatrutide simultaneously activates three receptors: GLP-1R (glucagon-like peptide-1 receptor) for appetite suppression and insulin secretion, GIPR (glucose-dependent insulinotropic polypeptide receptor) for potentiation of GLP-1 effects and direct adipocyte lipolysis, and GcgR (glucagon receptor) for increased energy expenditure, hepatic glycogenolysis, and...
What It Is
Retatrutide simultaneously activates three receptors: GLP-1R (glucagon-like peptide-1 receptor) for appetite suppression and insulin secretion, GIPR (glucose-dependent insulinotropic polypeptide receptor) for potentiation of GLP-1 effects and direct adipocyte lipolysis, and GcgR (glucagon receptor) for increased energy expenditure, hepatic glycogenolysis, and additional fat oxidation. The triple agonism produces additive and synergistic metabolic effects including greater appetite reduction, increased thermogenesis from glucagon signaling, and enhanced lipid oxidation compared to dual or single agonists. It is administered once weekly via subcutaneous injection.
Supplies Needed
Reconstitution solvent
Subcutaneous injection
Sterilization
Storage
Store at -20C for up to 2 years. Protect from light.
Refrigerate at 2-8C; use within 30 days.
This information is provided for educational and research purposes only. Not approved for human consumption by the FDA or any regulatory body. Always consult a qualified medical professional.
Dosing Protocols
Timing: Same day each week; any time of day. Titrate up slowly to minimize GI side effects; start at 2 mg for 4 weeks before increasing
↓ Apply these values to the reconstitution calculatorTiming: Same day each week. Titrate from 2 mg to 4 mg to 8 mg at 4-week intervals; 8 mg produced the highest weight loss in Phase 2
↓ Apply these values to the reconstitution calculatorTiming: Same day each week. Maximum dose studied in Phase 2; 24% average body weight loss at 48 weeks in clinical trials
↓ Apply these values to the reconstitution calculatorWeekly Timeline
| Week | Expected Effects |
|---|---|
| Week 4 | Significant appetite reduction; early weight loss of 2-4 kg |
| Week 12 | Substantial weight loss (8-12% body weight); improved glycemic control |
| Week 24 | Major weight loss milestone (~15-20% body weight at therapeutic doses) |
| Week 48 | Maximum weight loss achieved (up to 24% at highest doses); significant metabolic improvements |
Reconstitution Calculator
1 unit on U-100 syringe = 0.01 mL · Always label your vial after reconstitution
Injection Technique & Reconstitution
- Remove flip-top cap from the vial
- Swab rubber stopper with alcohol swab
- Draw appropriate volume of bacteriostatic water
- Inject slowly down the vial wall
- Gently swirl until dissolved
- Label with date; refrigerate at 2-8C
Use our free dosing calculator to get the exact syringe units for your vial size and dose.
Mechanism of Action
Retatrutide simultaneously activates three receptors: GLP-1R (glucagon-like peptide-1 receptor) for appetite suppression and insulin secretion, GIPR (glucose-dependent insulinotropic polypeptide receptor) for potentiation of GLP-1 effects and direct adipocyte lipolysis, and GcgR (glucagon receptor) for increased energy expenditure, hepatic glycogenolysis, and additional fat oxidation. The triple agonism produces additive and synergistic metabolic effects including greater appetite reduction, increased thermogenesis from glucagon signaling, and enhanced lipid oxidation compared to dual or single agonists. It is administered once weekly via subcutaneous injection.
Key Research Papers
Phase 2 randomized trial showing 24.2% body weight reduction at 12 mg weekly dose over 48 weeks - the largest weight loss ever reported in a randomized obesity drug trial.
View on PubMed →Stacks Well With
Add NNMT inhibition and NAD+ elevation to Retatrutide's appetite suppression and metabolic effects for comprehensive fat loss from multiple pathways.
BPC-157 helps manage GI side effects common with GLP-1 agonists by protecting gut mucosa and reducing nausea.
Frequently Asked Questions
Retatrutide is an experimental once-weekly injectable peptide that simultaneously activates GLP-1, GIP, and glucagon receptors. Phase 2 trials showed up to 24% body weight loss at 48 weeks - the highest ever seen in obesity drug trials as of 2024.
Tirzepatide activates GLP-1R and GIPR (dual agonist). Retatrutide additionally activates the glucagon receptor (GcgR), which increases energy expenditure and fat oxidation beyond what dual agonism achieves. This produces superior weight loss.
As of early 2025, Retatrutide is in Phase 3 clinical trials and is not yet FDA approved. It is available as a research compound only.
Legal Status by Region
This information is provided for educational and research purposes only. Not approved for human consumption by the FDA or any regulatory body. Always consult a qualified medical professional.