Retatrutide

Triple GLP-1/GIP/Glucagon Receptor Agonist

Retatrutide hits three receptors instead of one or two. GLP-1 kills appetite, GIP improves insulin sensitivity, glucagon burns liver fat and increases energy expenditure. The Phase 2 results in the New England Journal of Medicine were staggering — 24.2% weight loss at the top dose, with half the participants losing 25%+ of body weight. GI side effects are real at higher doses but manageable if you titrate slowly. Phase 3 (TRIUMPH) is underway. This is the one everyone in the weight loss space is watching.

Protocol

Dose: 1mg-12mg per week (titrated up over months) | Frequency: Once weekly | Cycle: Ongoing (not cycled) | Route: SubQ

Reconstitution: 2mL bacteriostatic water per 10mg vial for compounded versions. Use our free reconstitution calculator for exact syringe units.

Effects

• Weight loss (93%) — 24.2% body weight loss at the highest dose in 48-week Phase 2 trial — unprecedented numbers
• Appetite suppression (90%) — Triple-receptor activation produces the most complete appetite suppression of any peptide in this class
• Liver fat reduction (75%) — Up to 82.4% reduction in liver fat at the highest dose — the glucagon receptor activation drives this
• Improved metabolic markers (70%) — Significant improvements in blood sugar, insulin resistance, and lipid profiles

Side Effects

• Nausea (60%) — Up to 60% at the top dose (12mg). This is why you titrate slowly. Rushing the escalation is asking for a bad time.
• Diarrhea (20%) — About 1 in 5 people across all dose levels. Usually manageable, not usually the reason people stop.
• Vomiting (18%) — Hits hardest during dose escalation. Slow. Down.
• Constipation (12%) — Less common than with sema or tirz. Hydrate.
• Decreased appetite (10%) — Listed as a 'side effect' in trials. For most people running this, that's literally the point.

Evidence

Emerging evidence — The most-hyped weight loss peptide of 2025-26. Phase 2 trial published in NEJM showed 24.2% body weight loss at the highest dose over 48 weeks — the biggest number any obesity drug has posted. Phase 3 trials (TRIUMPH) are underway. Not yet approved, but the Phase 2 data broke the internet for a reason.

Approval status: Not approved

References

1. Jastreboff AM et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial N Engl J Med, 2023. PMID: 37366315
2. Sanyal AJ et al. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial Nat Med, 2024. PMID: 38858523
3. Doggrell SA et al. Is retatrutide (LY3437943), a GLP-1, GIP, and glucagon receptor agonist a step forward in the treatment of diabetes and obesity? Expert Opin Investig Drugs, 2023. PMID: 37086147
4. Doggrell SA et al. Retatrutide showing promise in obesity (and type 2 diabetes) Expert Opin Investig Drugs, 2023. PMID: 37947489
5. Ganamurali N et al. The Triple-Agonist Revolution: Retatrutide and the Paradigm Shift in Multi-Hormonal Pharmacotherapy for Obesity and Cardiometabolic Comorbidities Clin Pharmacol Drug Dev, 2026. PMID: 41545327

Storage

• Lyophilized: Refrigerate at 2-8C. Stable for 6+ months sealed.
• Reconstituted: Refrigerate. Use within 28 days.
• Water: Bacteriostatic water, 2mL per 10mg vial for compounded versions.
• Needle: 30-31 gauge, 0.5 inch for subcutaneous injection

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These statements have not been evaluated by the FDA. This content is for educational purposes only and is not intended to diagnose, treat, cure, or prevent any disease. Consult a healthcare professional before starting any protocol.

vialprep research · Sources: PubMed, FDA, peer-reviewed trials · How we verify