Retatrutide Dosing Guide & Protocols (2026)
Retatrutide dosing guide with community protocols, clinical trial escalation (1-12mg weekly), and safety.
Retatrutide is one of the most potent metabolic peptides studied to date — a triple-agonist that targets GLP-1 + GIP + glucagon receptors simultaneously. Early human trials have shown unmatched weight-loss potential, with subjects losing up to 24.2% of body weight in 48 weeks at higher doses.
Retatrutide is not FDA-approved. Everything below reflects published clinical trials and community protocols. This is not medical advice.
Quick Reference: Community Dosing
If you're here for the practical protocol, here it is:
| Parameter | Standard Protocol |
|---|---|
| Dose | 0.5 mg per injection |
| Route | Subcutaneous injection (abdomen or thigh) |
| Frequency | 3 times per week (Monday/Wednesday/Friday) |
| Cycle | 8 weeks on, 8 weeks off (or until goal weight) |
| Vial size | 12 mg, 24 mg, or 60 mg (multi-week supply) |
| Reconstitution | 2-5 mL bacteriostatic water depending on vial size |
| Storage | Refrigerate, use within 28 days |
Most people use: 0.5 mg (10 units on 1mL insulin syringe) three times per week, for a total weekly dose of 1.5 mg. Some start at 0.25 mg for the first week to assess tolerance.
For the full Retatrutide peptide profile, vendor pricing, and comparisons, see our Retatrutide peptide page.
Loading vs Maintenance
Community retatrutide protocols typically use consistent dosing rather than formal loading phases:
Start Low: Many begin with 0.25 mg for the first week to assess GI tolerability, then increase to 0.5 mg if well-tolerated.
Standard Protocol: 0.5 mg three times per week (1.5 mg total weekly) throughout the protocol. Unlike clinical trials that escalated doses, community protocols often maintain this conservative level.
Duration Options:
- Fixed cycle: 8 weeks on, 8 weeks off
- Goal-oriented: Continue until target weight loss, then cycle off
- Maintenance: Some use lower frequency (2x/week) once goals are achieved
Routes of Administration
Subcutaneous Injection (Only Route)
Retatrutide is a peptide that requires injection — it cannot be taken orally.
- Sites: Abdomen, thigh, or anywhere with subcutaneous fat
- Volume: Typically 0.1-0.2 mL with insulin syringe
- Rotation: Rotate injection sites to prevent lipodystrophy
- Timing: Can be taken any time of day, with or without food
Frequency Patterns
3x per week: Most common pattern (M/W/F or T/Th/Sat) for 1.5mg total weekly Weekly: Some use single weekly injection of 1.5mg (following clinical trial pattern) 2x per week: Used by some for maintenance phases at 0.5mg each (1mg total)
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Where These Numbers Come From: Clinical Context
The community doses above represent a conservative approach compared to clinical trials — here's the bridge:
Clinical Trial Doses (Phase 2 NEJM Study)
The landmark Phase 2 trial used escalating weekly doses:
| Timeframe | Clinical Trial Dose | Weekly Total |
|---|---|---|
| Weeks 0–4 | 1 mg weekly | 1 mg/week |
| Weeks 4–8 | 4 mg weekly | 4 mg/week |
| Weeks 8–12 | 8 mg weekly | 8 mg/week |
| Weeks 12–48 | 12 mg weekly | 12 mg/week |
Maximum weight loss: 24.2% at 12 mg weekly dose in the 48-week trial.
Why Community Doses Are Lower
Clinical trials used once-weekly injection escalating to 12mg/week for maximum weight loss in a controlled medical setting. Community protocols use 1.5mg/week (0.5mg × 3) for several reasons:
- No FDA approval: Retatrutide isn't approved, so users titrate conservatively without medical supervision
- Side effect management: Lower doses reduce GI side effects (nausea, vomiting) that were dose-limiting in trials
- Starting point: The clinical trial began at 1mg/week — community protocols often start lower
- Split dosing: 3x/week may provide more stable levels than weekly bolus
- Individual response: Many see significant effects at 1.5mg/week total dose
Research Vial Confusion
Searches for "retatrutide 24mg" and "retatrutide 60mg" reflect confusion about vial sizing:
| Vial Size | Does NOT Equal | Actually Provides |
|---|---|---|
| 12 mg vial | 12mg dose | 24 doses of 0.5mg |
| 24 mg vial | 24mg dose | 48 doses of 0.5mg |
| 60 mg vial | 60mg dose | 120 doses of 0.5mg |
These are total vial contents for multi-week protocols, not individual doses.
Mechanism of Action
Retatrutide's unique triple-agonist mechanism creates multiplicative metabolic effects:
GLP-1 receptor activation — Appetite suppression, delayed gastric emptying, improved insulin sensitivity. Same pathway as semaglutide and liraglutide.
GIP receptor activation — Enhanced insulin secretion, improved GLP-1 tolerability, additional metabolic benefits. Shared with tirzepatide.
Glucagon receptor activation — Increased energy expenditure, enhanced fat oxidation, thermogenic effects. This is unique to retatrutide among approved/investigational incretin therapies.
The combination creates effects that are multiplicative, not just additive:
- Appetite suppression (GLP-1) + insulin optimization (GIP) + metabolic acceleration (glucagon)
- Weight loss + body composition improvement + energy expenditure increase
This triple mechanism explains why retatrutide achieved 24.2% weight loss compared to ~15% for single-agonist GLP-1 drugs and ~22% for dual-agonist tirzepatide.
Side Effects & Safety
Retatrutide's side effect profile resembles high-potency incretin therapy, with GI effects dominating:
Common Side Effects (From Clinical Trials)
Nausea — Most common, affecting ~33% in high-dose groups. Dose-dependent and typically improves over time.
GI effects — Vomiting, diarrhea, constipation, and slowed gastric emptying typical of GLP-1 agonists.
Heart rate changes — Transient increases observed, peaked at 24 weeks then declined in trials.
Injection site reactions — Mild redness or irritation at injection sites.
Safety Observations
- No major safety signals in 48-week trial up to 12mg weekly
- Lower starting doses (2mg vs 4mg) partially reduced GI side effects in trials
- Rapid weight loss may increase gallbladder-related risks (common with any rapid weight loss)
- Long-term safety data limited to 48-week trial duration
Community Reports at 1.5mg/week
At the lower community doses, side effects appear milder:
- Less nausea than clinical trial high-dose groups
- Manageable GI effects with gradual dose increases
- Generally well-tolerated when started at 0.25mg
Stacking Retatrutide
Due to retatrutide's potent multi-pathway effects, stacking is less common than with single-mechanism peptides.
Considerations for Stacking
Metabolic overlap: Retatrutide already hits three major metabolic pathways, leaving fewer complementary targets.
Side effect amplification: Adding other GI-affecting compounds may worsen tolerability.
Complexity: Retatrutide's effects are so comprehensive that adding other weight loss peptides may be unnecessary.
Potential Combinations
Retatrutide + BPC-157: For users concerned about potential GI irritation, BPC-157 may provide gut protection.
Retatrutide + CJC-1295/Ipamorelin: Some combine with growth hormone peptides for body composition benefits, though evidence is limited.
Retatrutide + Thyroid: T3/T4 optimization may complement retatrutide's metabolic effects.
Frequently Asked Questions
What is the standard retatrutide dose for weight loss?
The most common community protocol is 0.5 mg, 3 times per week (total 1.5mg/week). This is lower than clinical trials that escalated to 12mg/week, since retatrutide isn't FDA-approved and users titrate conservatively.
Why are research vials sold as 12mg, 24mg, or 60mg?
These are total vial contents for multi-week protocols, not single doses. A 24mg vial provides multiple 0.5mg doses. Clinical trials used weekly injections up to 12mg, not these vial totals.
How does retatrutide compare to tirzepatide for weight loss?
Based on Phase 2 data, retatrutide showed greater weight loss (24.2% max vs ~22% for tirzepatide). Retatrutide is a triple agonist (GLP-1 + GIP + glucagon) while tirzepatide is dual (GLP-1 + GIP).
Is retatrutide FDA-approved?
No — retatrutide is investigational. Phase 3 trials are ongoing. All dosing information reflects research protocols and community use, not approved medical guidance.
Should I start at 0.5mg or lower?
Many start at 0.25mg for the first week to assess tolerance, then increase to 0.5mg. Clinical trials started at 1mg but showed better tolerability with lower starting doses.
What are the main side effects of retatrutide?
Similar to other GLP-1 agonists: nausea (dose-dependent), vomiting, diarrhea, constipation, and slowed gastric emptying. Clinical trials showed ~33% nausea in high-dose groups.
Can retatrutide be taken orally?
No — retatrutide is a peptide that would be destroyed by digestive enzymes. All protocols use subcutaneous injection, typically weekly or split into 3x/week.
How long should I run retatrutide?
Clinical trials ran 48 weeks with continued benefits. Community protocols vary: some use 8-week cycles with breaks, others continue until goal weight is achieved. No long-term safety data beyond 48 weeks exists.
Related Guides
- Retatrutide Peptide Page — Vendor pricing, comparisons, and full peptide profile
- Tirzepatide Dosing Guide — Dual agonist alternative to retatrutide
- Semaglutide Dosing Guide — Single GLP-1 agonist reference
- Retatrutide Phase 3 Results — Latest clinical trial updates
- How Peptides Work — Understanding incretin mechanisms
- Peptide Calculator — Dosing and reconstitution calculator
References
| Citation | Topic | PMID |
|---|---|---|
| Jastreboff AM, et al., N Engl J Med (2023) | Phase 2 trial: Triple-hormone agonist for obesity | 37366315 |
Looking for retatrutide pricing? Check our Retatrutide peptide page for current prices from verified vendors.
This article is for educational and informational purposes only. It is not medical advice and should not be used to diagnose, treat, or prevent any condition. Consult a licensed healthcare provider before using any peptide.