Retatrutide
The most potent incretin triple agonist in Phase III — GIP + GLP-1 + Glucagon receptor activation for superior weight loss and metabolic benefit.
Research facts
| Half-life | ~6 days |
|---|---|
| Route | SubQ |
| Typical dose | 1–12 mg/week |
| Frequency | Once weekly |
| Solvent | Pre-filled pen or reconstituted |
| pH | 5.0–7.0 |
| Stability | Per manufacturer / 30 days +4°C |
Mechanism of action
Retatrutide (LY3437943) is a first-in-class triple agonist targeting GIP (glucose-dependent insulinotropic peptide), GLP-1 (glucagon-like peptide 1), and glucagon receptors simultaneously. This tripartite mechanism addresses energy balance from multiple angles simultaneously.
GLP-1R agonism reduces appetite via hypothalamic satiety signalling, slows gastric emptying, and increases insulin secretion. GIPR agonism synergises with GLP-1 for enhanced incretin effect and also targets adipose GIPR for direct fat mobilisation. Glucagon receptor agonism drives hepatic glucose output reduction and enhances energy expenditure via thermogenic brown adipose activation.
Phase II trials showed 24% body weight reduction at highest doses over 48 weeks — substantially exceeding Tirzepatide (20%) and Semaglutide (15%). Phase III trials (TRIUMPH programme) are ongoing. The additional glucagon component may explain superior fat loss vs. dual agonists.
Documented effects (research-model)
- 24% mean body weight reduction in Phase II (highest dose, 48 weeks)
- Superior visceral fat reduction vs. dual/single agonists
- HbA1c and insulin resistance improvement
- Cardiovascular risk factor improvement (lipids, blood pressure)
- Liver fat reduction comparable to Tesamorelin
- Potential NASH/MAFLD therapeutic application
Research protocols
| Protocol | Dose | Frequency | Cycle | Vial |
|---|---|---|---|---|
| Standard | 2–4 mg/week SubQ escalation | Once weekly | 24–48 weeks | Per preparation |
| Maintenance | 8–12 mg/week | Once weekly | Ongoing once weight goal achieved | Per preparation |
Research context only. Not medical advice. Consult a qualified healthcare professional before any protocol decision.
Synergies
- Tesamorelin MODERATE
Both target metabolic/fat endpoints via different mechanisms. Retatrutide is appetite/incretin-driven; Tesamorelin is GH-driven lipolysis.
Myths & misconceptions
Evidence gaps
- Phase III data not yet fully published (trials ongoing at time of this profile).
- Long-term safety beyond 48 weeks not characterised.
- Whether glucagon component adds cardiovascular benefit or risk compared to dual agonists is under investigation.
Safety notes
GI side effects (nausea, vomiting, diarrhoea) common with dose escalation. Contraindicated in personal/family history of medullary thyroid carcinoma or MEN2. Monitor HbA1c, renal function, gallbladder. Slow titration essential.
Biomarkers to monitor
Primary-source citations
- PMID 37213278 — Triple Hormone Receptor Agonist Retatrutide for Obesity — Phase 2 Trial (N Engl J Med. 2023)
Frequently asked
What is Retatrutide?
Retatrutide (LY3437943 — GIP/GLP-1/Glucagon Triple Agonist) is a research compound classified in our library as Tier A — Reproducible human RCT data.. The most potent incretin triple agonist in Phase III — GIP + GLP-1 + Glucagon receptor activation for superior weight loss and metabolic benefit.
What is the evidence tier for Retatrutide?
We classify Retatrutide as Tier A: Reproducible human RCT data. See our full peptide evidence tiers explainer for how we assign S/A/B/C/D.
What is the research dose of Retatrutide?
For Retatrutide, typical research dose is 1–12 mg/week, route is SubQ, half-life is ~6 days. Protocols vary by research goal — see the protocols section on this page for standard and advanced dosing schedules. Research use only, not medical advice.
Is Retatrutide safe?
GI side effects (nausea, vomiting, diarrhoea) common with dose escalation. Contraindicated in personal/family history of medullary thyroid carcinoma or MEN2. Research context only — no compound on this site is approved for human therapeutic use unless explicitly noted.