Retatrutide
Retatrutide is a novel triple-receptor agonist targeting GLP-1, GIP, and glucagon (GCG) receptors simultaneously. Developed by Eli Lilly, it represents the next frontier in incretin-based therapies. The addition of glucagon receptor activation increases energy expenditure and hepatic fat oxidation beyond what dual agonists achieve. Phase 2 trials demonstrated unprecedented weight loss of approximately 24% of body weight at 48 weeks at the highest dose — the most potent result seen in any obesity trial to date. It also showed dramatic reductions in liver fat (up to 86%), making it promising for MASH/NAFLD. Retatrutide is currently in Phase 3 clinical trials and is not yet FDA-approved.
Frequency
Once weekly
Cycle Length
Under investigation. Phase 2 trials ran 48 weeks. Use only under medical supervision.
Route
Subcutaneous
Research Level
Experimental
Goals
Dosing Protocol
Titrate up from 2 mg to 12 mg weekly. Starting dose is 2 mg. Same day every week. Research compound — follow provider guidance.
Reconstitution
Research compound — follow provider or manufacturer instructions. Compounded vials: depends on vial concentration strength. Refrigerate.
Timing
Once weekly at a consistent time. Clinical trials did not specify time of day.
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Potential Side Effects
- Nausea
- Diarrhea
- Vomiting
- Constipation
- Decreased appetite
- Elevated heart rate
- Injection site reactions
- Muscle loss — mitigate with regular strength training and a high-protein diet
- Gallbladder issues (risk increases with rapid weight loss)
- Contraindicated with personal or family history of medullary thyroid carcinoma (MTC)
- Limited long-term safety data
Important Warnings
- Not FDA-approved — Phase 3 clinical trials ongoing
- Contraindicated with personal or family history of medullary thyroid carcinoma (MTC)
- Most potent weight loss agent — requires careful medical monitoring
- Not for use during pregnancy
Works Well With
Research References
- Jastreboff AM, et al. N Engl J Med. 2023;389(6):514-526. doi:10.1056/NEJMoa2301972
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Medical Disclaimer: This information is for educational purposes only and is not intended as medical advice. Retatrutide may be regulated differently in various jurisdictions. Always consult with a qualified healthcare provider before beginning any peptide protocol. PepStack Pro does not sell peptides or provide medical advice. Content reviewed by Dr. Seth Miller, MD.