Retatrutide
The Triple Agonist Peptide Redefining Weight Loss and Metabolic Reversal
What is Retatrutide?
Retatrutide (also known by its development code LY3437943) is a novel multi-agonist peptide currently in late-stage clinical trials for the treatment of obesity, type 2 diabetes, and cardiometabolic disease. Developed by Eli Lilly, Retatrutide is a triple hormone receptor agonist that activates the GLP-1, GIP, and glucagon receptors—offering a new frontier in metabolic peptide science.
As a powerful investigational agent, Retatrutide builds on the success of GLP-1 receptor agonists like semaglutide and tirzepatide, showing unprecedented weight loss outcomes and improved glycemic control in early clinical data. While not yet FDA approved, it has become a focal point of advanced peptide research in weight management and metabolic optimization.
How Does Retatrutide Work?
Retatrutide simultaneously targets three distinct metabolic hormone pathways to amplify fat burning, insulin sensitivity, and appetite suppression:
Mechanism of Action:
- GLP-1 receptor activation – Enhances insulin secretion, slows gastric emptying, reduces appetite
- GIP receptor activation – Improves insulin sensitivity and supports beta cell function
- Glucagon receptor activation – Stimulates hepatic fat oxidation and energy expenditure
Together, this triple-receptor synergy promotes rapid weight loss, improved metabolic flexibility, and superior glycemic control compared to single- or dual-agonist approaches.
Benefits of Retatrutide in Research
⚖️ Unmatched Weight Loss Potential
- Up to 24.2% total body weight reduction reported in early clinical trials
- More effective than semaglutide (Ozempic/Wegovy) or tirzepatide (Mounjaro)
- Reduces both visceral and subcutaneous fat
🩸 Glycemic Control & Insulin Sensitivity
- Improves HbA1c in type 2 diabetes models
- Reduces fasting insulin and glucose levels
- Enhances whole-body insulin responsiveness
🔥 Fat Oxidation & Energy Expenditure
- Stimulates lipolysis via glucagon receptor
- Promotes lean mass preservation during weight loss
- May offer metabolic benefits in NAFLD and PCOS models
Retatrutide vs Semaglutide vs Tirzepatide
| Feature | Retatrutide | Tirzepatide | Semaglutide |
|---|---|---|---|
| Mechanism | GLP-1 + GIP + Glucagon | GLP-1 + GIP | GLP-1 only |
| Weight Loss (avg) | ~24% | ~21% | ~15% |
| Appetite Suppression | Strong | Moderate–Strong | Strong |
| Energy Expenditure | High | Low–Moderate | Low |
| Glycemic Improvement | Excellent | Excellent | Excellent |
| Dosing Frequency | Weekly (under trial) | Weekly | Weekly |
Retatrutide’s triple agonism makes it a standout candidate for future obesity and metabolic disorder therapies.
Suggested Dosage & Protocol (Research Use Only)
Retatrutide is still under clinical investigation. Research dosing is based on early-phase trial data:
Preclinical Research Dosing:
- Weekly subcutaneous injection
- Dose range: 0.5mg to 12mg weekly depending on study arm
- Titration over 4–8 weeks to mitigate gastrointestinal side effects
Cycle Duration:
- Research trials span 26–48 weeks, with sustained efficacy
Safety Profile of Retatrutide
As a potent incretin/glucagon modulator, Retatrutide has shown good tolerability, but side effects may mirror other GLP-1 agonists.
Common Side Effects:
- Nausea, vomiting, and diarrhea (dose-dependent)
- Constipation or transient appetite suppression
- Mild fatigue or dizziness during titration
Less Common Effects:
- Gallbladder issues (similar to GLP-1 class)
- Elevations in heart rate in some participants
- Requires cautious use in those with personal or family history of medullary thyroid carcinoma
Reference:
- Jastreboff AM et al., “Triple-hormone-receptor agonist Retatrutide in obesity.” NEJM, 2023. https://www.nejm.org/doi/full/10.1056/NEJMoa2301972
Storage Instructions
- Store lyophilized Retatrutide at 2–8°C in a temperature-controlled environment
- Reconstitute with bacteriostatic water if provided in powder form
- Use within 14–28 days after reconstitution
Ideal Stack Recommendations
While Retatrutide is typically used alone in trials, researchers may explore metabolic stack combinations:
- 5-Amino-1MQ – for synergistic fat metabolism and NAD+ regulation
- MOTS-c – to support mitochondrial energy production
- NAD+ – for cellular recovery during caloric restriction
- GHK-Cu – to aid skin elasticity and recovery during rapid weight loss
Is Retatrutide Right for Your Research?
If your focus includes obesity, metabolic syndrome, NAFLD, insulin resistance, or cardiometabolic optimization, Retatrutide represents a cutting-edge investigational compound. Its triple-agonist design offers a multifactorial approach to weight loss, insulin sensitivity, and energy modulation.
Final Thoughts
Retatrutide is a next-generation metabolic peptide with the potential to redefine obesity treatment and metabolic regulation. With stronger outcomes than GLP-1 or GIP dual therapies, it promises more comprehensive results with fewer trade-offs.
Lab of RAD provides research-grade Retatrutide to support clinical and preclinical research into weight loss, diabetes, and hormone-driven metabolism.
⚠️ FDA Disclaimer
This information is provided for educational and research purposes only. Retatrutide has not been evaluated or approved by the U.S. Food and Drug Administration (FDA). It is not intended to diagnose, treat, cure, or prevent any disease.
Lab of RAD peptides are sold for laboratory research use only and are not for human consumption.