GLP-1 Weight Loss
Retatrutide
A triple agonist that activates GLP-1, GIP, and glucagon receptors at once — the most aggressive weight-loss compound in clinical development. Phase 2 data showed 24% average body weight loss at 48 weeks, the highest ever recorded in a pharmaceutical trial. Physician-supervised for California patients.
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Physician-reviewed peptide therapy, prescribed only when appropriate.
Protocol at a glance
- Dose
- 1–12 mg (titrated)
- Route
- Subcutaneous injection
- Frequency
- Once weekly
- Course
- Titrated over several months
Physician-reviewed. Prescribed only if appropriate after a telehealth consult — full refund if a licensed clinician determines it isn't right for you.
Why patients choose it
Why patients choose retatrutide
Three pathways, not one
Activates GLP-1, GIP, and glucagon receptors together — adding metabolic rate to appetite suppression for a compounding effect.
Highest trial weight loss
Phase 2 patients on the top dose lost an average of 24.2% of body weight at 48 weeks — the highest figure ever recorded in a pharmaceutical trial.
When dual agonists fall short
An option for patients who responded poorly or partially to semaglutide or tirzepatide and need more aggressive intervention.
Overview
What retatrutide is
Retatrutide is a triple agonist that stacks three receptor pathways simultaneously, which is what sets it apart from the single- and dual-agonist GLP-1 therapies that came before it:
- GLP-1 receptor: Suppresses appetite, slows gastric emptying, improves insulin secretion
- GIP receptor: Enhances insulin response, improves fat metabolism, reduces GI side effects of GLP-1
- Glucagon receptor: Increases energy expenditure (metabolic rate), promotes fat oxidation in the liver
The glucagon component is the key differentiator. While glucagon alone raises blood sugar, in combination with GLP-1 its metabolic effects dominate — increasing calorie burn without significant glycemic impact.
Candidacy
Who it's for
Retatrutide may be considered for:
- Patients who responded poorly or partially to semaglutide or tirzepatide
- Individuals with significant obesity (BMI 35+) who need aggressive intervention
- Patients with metabolic syndrome, NAFLD, or significant insulin resistance
- Those seeking the most aggressive pharmaceutical weight loss option available
Not FDA approved. Discuss the risk/benefit profile with your physician — available data is Phase 2 only.
What to expect
How it unfolds, week by week
01
First weeks
Treatment begins at a low 1mg weekly dose and titrates upward gradually, the same approach used with tirzepatide to minimize GI side effects.
02
Titration months
The dose is stepped up over several months toward the therapeutic range (up to 12mg weekly), with appetite suppression building as the dose rises.
03
Week 48 (trial endpoint)
In Phase 2 trials, patients on the highest dose lost an average of 24.2% of body weight by 48 weeks, with about 26% losing 30% or more.
Retatrutide vs. tirzepatide vs. semaglutide
| Semaglutide | Tirzepatide | Retatrutide | |
|---|---|---|---|
| Targets | GLP-1 | GLP-1, GIP | GLP-1, GIP, Glucagon |
| Peak trial weight loss | ~15% at 68 weeks | ~21% at 72 weeks | ~24% at 48 weeks |
| FDA status | Approved | Approved | In Phase 3 trials — not approved |
Phase 2 data. Not head-to-head trials — populations and durations differ. Retatrutide not yet FDA approved.
Safety
Side effects & contraindications
The side effect profile is similar to other GLP-1-based therapies. The most commonly reported, particularly during dose escalation:
- Nausea, vomiting, and diarrhea
- Decreased appetite
- Heart rate increases were observed in some patients
In Phase 2 trials, the high-dose group had higher GI side effect rates, and the glucagon component may cause slightly more nausea than dual agonists. Long-term safety data is still accumulating. Discuss the risk/benefit profile with your prescribing physician before starting.
FAQ
Retatrutide questions
Related peptides
Often explored together
Tirzepatide
Dual GLP-1/GIP agonist — the approved option many patients start with.
Learn more →Semaglutide
GLP-1 agonist; the original next-generation weight-loss peptide.
Learn more →Tesamorelin
GHRH analogue studied for visceral fat reduction.
Learn more →AOD-9604
A fragment of HGH studied for fat metabolism.
Learn more →Ask about retatrutide in California
Speak with a physician about whether retatrutide is appropriate for you. No clinic visit required.
Check Your EligibilityRetatrutide
Physician-reviewed