Protocol Overview
Retatrutide (LY3437943) is a once-weekly injectable peptide that simultaneously activates three receptors: GLP-1 (glucagon-like peptide-1), GIP (glucose-dependent insulinotropic polypeptide), and glucagon receptors. This triple-agonist mechanism distinguishes it from semaglutide (GLP-1 mono-agonist) and tirzepatide (GLP-1/GIP dual agonist).
Phase 2 clinical trials published in the New England Journal of Medicine (2023) showed mean weight loss of up to 24.2% at 48 weeks at the highest dose studied, making it among the most potent obesity research compounds in development.
Reconstitution
Recommended BAC water: 2 mL. Resulting concentration: 20 mg ÷ 2 mL = 10 mg/mL.
Dosing Schedule (Escalation Protocol)
| Week | Dose | Volume (2mL recon) | U-100 Units |
|---|---|---|---|
| 1–4 | 2 mg | 0.20 mL | 20 units |
| 5–8 | 4 mg | 0.40 mL | 40 units |
| 9–12 | 8 mg | 0.80 mL | 80 units |
| 13+ | 12 mg | 1.20 mL | 120 units (split dose) |
Frequency: Once weekly, subcutaneous injection. Dose escalation is used to minimize gastrointestinal side effects during initiation.
Safety Notes
Most common side effects in clinical trials: nausea, vomiting, diarrhea, constipation, and decreased appetite. These are most pronounced during dose escalation and typically improve with maintenance dosing. Retatrutide carries a theoretical risk of thyroid C-cell tumors seen in rodent models with GLP-1 receptor agonists; relevance to humans is unknown. Not for use in individuals with personal or family history of medullary thyroid carcinoma.