Retatrutide (10mg)
Retatrutide is an investigational triple agonist peptide (targeting GLP-1, GIP, and glucagon receptors) in development for obesity and T2DM. Phase 2 trials showed up to 24% body weight change at 48 weeks, while new Phase 3 data (TRIUMPH-4, 2026) reported 28.7% weight change at 68 weeks—the highest reported performance in a Phase 3 obesity trial. This protocol outlines a weekly subcutaneous research approach with gradual titration.
Reviewed by the AllPeptides.eu Editorial Team·Last reviewed: 2026-06-16
Educational information. Not medical advice, and no efficacy claim is implied. Regulatory approval is not a use recommendation by AllPeptides.eu.
⚠️ For informational/educational purposes only. Not medical advice. We do not sell any products. Self-treatment carries serious risks — consult a healthcare professional. Disclaimer
Research monograph
See the full Retatrutide encyclopedia page with mechanism, evidence tier, related variants and research context.
How It Works
Retatrutide's unique **mechanism of action** stems from its triple agonist design. By activating GLP-1 and GIP receptors, it influences glucose-dependent insulin secretion and appetite signaling, similar to the broader incretin research field. Additionally, **glucagon receptor agonism** is research-associated with metabolic rate and energy expenditure. Its ~6-day half-life supports a weekly research dosing model.
Quick Start
- Reconstitution: Add 1.0 mL of bacteriostatic water → ~10.0 mg/mL concentration.
- Weekly Range: 2–8 mg once weekly (gradual ramp-up over 8–12 weeks).
- Storage: Lyophilized: freeze at −20 °C; after reconstitution, refrigerate at 2–8 °C for up to 4 weeks.
Typical / Gradual Approach (1 mL = ~10.0 mg/mL)
Route: Subcutaneous | Frequency: Once weekly
| Week | Dose | Units (per injection) |
|---|---|---|
| Weeks 1–4 | 2 mg (2000 mcg) | 20 Units (0.20 mL) |
| Weeks 5–8 | 4 mg (4000 mcg) | 40 Units (0.40 mL) |
| Weeks 9–12 | 6 mg (6000 mcg) | 60 Units (0.60 mL) |
| Weeks 13+ | 8 mg (8000 mcg) | 80 Units (0.80 mL) |
Studies report administration once weekly subcutaneously. All doses ≤10 mg are drawn from one reconstituted 10 mg vial with 1.0 mL reconstitution. For volumes >1.0 mL, split into 2 separate subcutaneous injections at different sites for proper absorption.
Related compounds
Reconstitution Steps
- Withdraw 1.0 mL of bacteriostatic water with a sterile syringe.
- Inject slowly down the side of the vial; avoid foaming.
- Gently swirl/roll until dissolved (do not shake vigorously).
- Note the date and refrigerate at 2–8 °C, protected from light.
- Use within 4 weeks of reconstitution.
Protocol Overview
- Objective: Support significant weight loss and metabolic improvements via triple receptor agonism.
- Schedule: Weekly subcutaneous injections for 12–48 weeks (clinical trials 36–48 wks).
- Storage: Lyophilized frozen at −20 °C; reconstituted refrigerated at 2–8 °C for up to 4 weeks.
Dosing Protocol
- Initiation: 2 mg weekly × 4 weeks to assess tolerability.
- Titration: Increase by 2–4 mg every 4 weeks as tolerated.
- Target: 6–8 mg weekly (standard); 12 mg weekly (advanced/aggressive).
- Frequency: Once weekly (subcutaneously), same day each week.
- Duration: Minimum 24 weeks; trials extended to 48 weeks.
- Break between cycles: After completing the cycle, a 6–8 week pause is recommended. Retatrutide (a GIP/GLP-1/Glucagon triple agonist) has a prolonged action (~6 day half-life)—a longer washout period is required.
Washout & Cycle Restart
When can I restart?
After completing the cycle, a 6–8 week pause is recommended. Retatrutide (a GIP/GLP-1/Glucagon triple agonist) has a prolonged action (~6 day half-life)—a longer washout period is required.
Minimum wait period: 6 weeks
Storage Instructions
- Lyophilized: Store at −20 °C in dry, dark conditions; stable for up to 24 months.
- Reconstituted: Refrigerate at 2–8 °C; use within 4 weeks.
- Allow vials to reach room temperature before opening.
- For extended storage, aliquot reconstituted solution and freeze at −20 °C; thaw only once before use.
Important Notes
- For doses >10 mg with 1.0 mL reconstitution, prepare multiple vials for the required volume.
- For volumes >1.0 mL, split into 2 separate injections at different sites.
- Gradual titration is essential to minimize gastrointestinal side effects; do not skip titration steps.
Potential Benefits & Side Effects
Potential Benefits:
- Exceptional Weight Change: In participants with obesity, a mean body weight change of 22–24% was recorded at 48 weeks on doses of 8–12 mg (Phase 2). In Phase 3 (TRIUMPH-4, 2026): 28.7% at 68 weeks.
- Glycemic Control: In patients with T2DM, HbA1c was reduced by 1.3–2.0%; ~82% achieved an HbA1c of ≤6.5%.
- Cardiometabolic Improvements: Reductions in blood pressure, LDL cholesterol, waist circumference, and liver fat (>80% resolution of hepatic steatosis).
- Universal Response: 100% of participants on 8–12 mg achieved at least 5% weight loss.
Potential Side Effects:
- Gastrointestinal: Nausea, vomiting, diarrhea—mild to moderate, mainly during dose escalation. Gradual titration significantly reduces symptoms.
- No severe hypoglycemia or serious adverse events reported in trials.
- Safety profile comparable to GLP-1 agonists when titrated properly.
⚠️ Serious Warnings & Long-Term Risks
The following warnings are based on published literature, FDA labels, and post-marketing surveillance. They do not constitute medical advice. Consult a healthcare professional.
Potential thyroid C-cell risk
As a triple GLP-1/GIP/Glucagon agonist, the same class-effect warning as semaglutide/tirzepatide is expected.
📄 Phase 2 Trial — NEJM 2023References
- The Lancet (2023) — Retatrutide in T2DM — Phase 2 (36 wks, HbA1c reductions, weight change)
View Source - NEJM (2023) — Triple agonist Retatrutide for obesity — Phase 2 (48 wks, up to 24% weight change)
View Source - Cell Metabolism (2022) — LY3437943 (Retatrutide): discovery to clinical proof of concept (GLP-1/GIP/glucagon triple agonist)
View Source - ClinicalTrials.gov — Study of Retatrutide in adults with obesity (NCT04881760)
View Source - Current Obesity Reports (2025) — Triple agonist therapies for obesity (titration strategies, GI side effect management)
View Source - TRIUMPH-4 Phase 3 (2026) — Retatrutide Phase 3: 28.7% weight change at 68 weeks — highest performance in an obesity trial.
View Source
Recommended Supplements
Vitamin B12 (Methylcobalamin)
Vitamin D3 + K2
Omega-3 Fish Oil (EPA/DHA)
Protein / Collagen
Fiber Supplement (Psyllium)
External Sources & Regulatory Status
Regulatory Approvals
Obesity / Type 2 diabetes
Obesity / Type 2 diabetes
Phase III clinical trials
Educational information. Not medical advice, and no efficacy claim is implied. Regulatory approval is not a use recommendation by AllPeptides.eu.
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