Retatrutide
Dosage Protocol
Retatrutide (LY3437943) is a once-weekly triple agonist targeting GLP-1, GIP, and glucagon receptors simultaneously — making it the most mechanistically comprehensive compound in the incretin agonist class. It is currently in Phase 3 clinical trials with no approved pharmaceutical formulation.
What is Retatrutide?
Retatrutide's triple-agonist mechanism simultaneously targets GLP-1R (appetite, insulin), GIPR (incretin enhancement, fat metabolism), and GCGR (energy expenditure, hepatic glucose output). The GCGR component distinguishes it from semaglutide and tirzepatide, theoretically increasing energy expenditure in addition to reducing caloric intake — a potentially additive mechanism not seen in dual agonists.
Phase 2 trial data reported substantial weight reduction at higher doses over 48 weeks. The compound is still in clinical development with no pharmaceutical formulation currently available. Research protocols are extrapolated from available trial data. Careful dose titration over many months is essential.
Dosing Schedule
Parameters documented in published preclinical and clinical research.
| Phase | Dose | Frequency | Duration | Notes |
|---|---|---|---|---|
| Start | 1 mg | Once weekly | Weeks 1–4 | Minimum tolerated dose. GI side effects most likely here. |
| Titrate | 2 mg | Once weekly | Weeks 5–8 | Increase every 4 weeks as tolerated. |
| Working dose | 4–8 mg | Once weekly | Weeks 9–24 | Range studied in Phase 2/3 trials. |
| High dose | 10–12 mg | Once weekly | Week 24+ | Highest doses from trial data. Advance only if prior stages well tolerated. |