Overview
In plain English
Retatrutide is the newest generation of weight-loss compound. Where semaglutide hits one receptor and tirzepatide hits two, retatrutide hits three.
The third one is the difference. GLP-1 and GIP reduce how much you eat; the glucagon receptor increases how much energy you burn. It is a once-weekly injection, titrated up slowly over about eight weeks.
- What it isA single molecule acting on GLP-1, GIP and glucagon receptors
- Mainly used forWeight loss and metabolic health
- Typical protocolOnce weekly, titrated 1mg → 9mg over 8+ weeks
How it works
What it actually does
Two of the three receptors work on the intake side: less appetite, slower stomach emptying, better insulin response to food. This is the same territory as semaglutide and tirzepatide.
The third — the glucagon receptor — works on the output side, in the liver, increasing energy expenditure and fat burning. That is what neither of the others does.
Titrate slowly. The gastrointestinal side effects are dose-related, and there is no requirement to reach the top dose if a lower one is working.
The science in detail
Retatrutide is a unimolecular agonist at three class B G-protein-coupled receptors: the glucose-dependent insulinotropic polypeptide receptor (GIPR), the glucagon-like peptide-1 receptor (GLP-1R) and the glucagon receptor (GCGR). Each is coupled principally to Gs, so agonism at all three raises intracellular cAMP in the relevant target tissues, but the tissue distribution of the three receptors is what produces the compound's distinct profile.
GLP-1R agonism acts on pancreatic beta cells to potentiate glucose-dependent insulin secretion, and on hindbrain and hypothalamic circuits governing satiety and gastric emptying. GIPR signalling contributes a further incretin effect at the beta cell and has additional actions in adipose tissue; its role in energy balance remains an area of active argument, since both GIPR agonism and antagonism have shown weight-lowering effects in different models. The glucagon receptor arm is the substantive point of difference. GCGR is expressed densely in hepatocytes, where cAMP-driven signalling raises hepatic lipid oxidation and energy expenditure. In principle this adds a catabolic, expenditure-side mechanism to the intake-side mechanisms supplied by GLP-1R and GIPR — a different axis of action from dual GIP/GLP-1 agonists such as tirzepatide, which lack glucagon receptor activity, and from selective GLP-1 agonists such as semaglutide.
The counterweight is that unopposed glucagon receptor agonism is hyperglycaemic. The design problem for triple agonists is therefore ratio: the incretin components must be sufficient to offset the glycaemic consequence of the glucagon component. Retatrutide's receptor potency ratios were selected on this basis.
Structurally, retatrutide is a synthetic peptide carrying a fatty diacid substitution that promotes reversible albumin binding, extending circulating half-life sufficiently for once-weekly administration in the clinical protocols in which it was studied. Non-canonical residues in the backbone reduce susceptibility to dipeptidyl peptidase-4 cleavage.
Evidence
What the research shows
Three receptors, one molecule
GLP-1 and GIP reduce intake; the glucagon arm raises energy expenditure.
Phase 2 obesity trial in NEJM
Results were published in the New England Journal of Medicine in 2023.
Also trialled in type 2 diabetes
A separate phase 2 trial was published in The Lancet in 2023.
The glucagon arm is the differentiator
Dual GIP/GLP-1 agonists such as tirzepatide have no glucagon receptor activity.
Mixing & dosage
How to mix and dose it
These are the mixing and dosage instructions supplied by Purist Peptides and the manufacturer for this product.
A 3ml vial of bacteriostatic water is included free with every peptide vial you order, so you have what you need to mix this on arrival.
Retatrutide 30mg (GLP-3RT)
Step 1 — mix your vial
- Draw up 3ml of bacteriostatic water into a syringe
- Wipe the rubber top of your vial with an alcohol swab and let it dry
- Insert the needle then slowly and carefully push the water down the inside wall of the vial — do not inject water straight onto the peptide powder
- Gently roll the vial between your palms until the powder dissolves completely
- Do not shake
- Allow to settle in the fridge for 5–10 minutes. The liquid should look clear
Step 2 — draw & inject your dose
Use a 1ml insulin syringe to draw and inject your dose. A 1ml syringe = 100 units.
With 3ml of water added, each 0.1ml (10 units) you draw = 1mg of Retatrutide.
| Stage | Dose | On the syringe |
|---|---|---|
| Week 1 | 1mg once weekly | 10 units |
| Week 2 | 1.5mg once weekly | 15 units |
| Weeks 3 to 4 | 3mg once weekly | 30 units |
| Weeks 5 to 6 | 4.5mg once weekly | 45 units |
| Weeks 7 to 8 | 6mg once weekly | 60 units |
| Week 9 onwards | 9mg (peak) once weekly | 90 units |
This 30mg schedule is the gentler ramp, intended for a first cycle.
Progress through each step only when comfortable at the current dose.
There is no requirement to reach the peak dose. Stay at the dose that works for you.
When to inject: Once weekly on the same day each week.
Cycle length: Continue at your comfortable maintenance dose for as long as needed. Reassess regularly.
Retatrutide 60mg (GLP-3RT)
Step 1 — mix your vial
- Draw up 2ml of bacteriostatic water into a syringe
- Wipe the rubber top of your vial with an alcohol swab and let it dry
- Insert the needle then slowly and carefully push the water down the inside wall of the vial — do not inject water straight onto the peptide powder
- Gently roll the vial between your palms until the powder dissolves completely
- Do not shake
- Allow to settle in the fridge for 5–10 minutes. The liquid should look clear
Step 2 — draw & inject your dose
Use a 1ml insulin syringe to draw and inject your dose. A 1ml syringe = 100 units.
With 2ml of water added, each 0.1ml (10 units) you draw = 3mg of Retatrutide.
| Stage | Dose | On the syringe |
|---|---|---|
| Weeks 1 to 2 | 1.5mg once weekly | 5 units |
| Weeks 3 to 4 | 3mg once weekly | 10 units |
| Weeks 5 to 6 | 6mg once weekly | 20 units |
| Weeks 7 to 8 | 9mg once weekly | 30 units |
| Week 9 onwards | 12mg (peak) once weekly | 40 units |
The 60mg schedule starts higher and peaks higher. It is intended for someone who has already completed a cycle, not for a first course.
Progress through each step only when comfortable at the current dose.
There is no requirement to reach the peak dose. Stay at the dose that works for you.
When to inject: Once weekly on the same day each week.
Cycle length: Continue at your comfortable maintenance dose for as long as needed. Reassess regularly.
How to inject
- Wipe your injection site with an alcohol swab and let it dry
- Pinch a small fold of skin on your abdomen
- Insert the needle at a 45-degree angle into the pinched skin
- Slowly push the plunger down until empty
- Pull the needle out and apply gentle pressure with the swab
- Dispose of the needle safely in a sharps container — never recap or reuse
Storage
Keep refrigerated at 2 to 6 degrees Celsius at all times after mixing. Do not freeze. Protect from light and label the vial with the date you reconstituted it. Discard any solution that is hazy, discoloured or contains particles.
For informational purposes only. This is not medical advice. Speak to a qualified healthcare professional before starting any compound.
Questions
Frequently asked questions
What distinguishes retatrutide from tirzepatide?
Tirzepatide is a dual agonist at the GIP and GLP-1 receptors. Retatrutide adds agonism at the glucagon receptor, which is expressed principally in the liver and is associated in research models with increased hepatic lipid oxidation and energy expenditure. The two compounds therefore differ in mechanism, not only in potency.
What has retatrutide been studied for?
Its published phase 2 programme covered obesity (Jastreboff et al., NEJM 2023) and type 2 diabetes (Rosenstock et al., Lancet 2023). Substudies have examined body composition change. Later-phase trials under the TRANSCEND programme have been reported. Purist supplies the compound for laboratory research only.
Why does the glucagon receptor component matter?
Glucagon receptor agonism on its own raises blood glucose. In a triple agonist the incretin components are intended to offset that effect, so the receptor potency ratio is a central design parameter. This balance is the principal subject of interest in the triple-agonist literature.
Is the 60mg vial a different compound to the 30mg vial?
No. Both vials contain the same lyophilised compound; they differ only in the mass supplied. The larger vial reduces the number of reconstitutions required across an extended research protocol.
How is purity verified?
Every batch is assayed by independent HPLC at Bioindustrial Services in Boksburg. We do not rely on the manufacturer's own certificate alone. The assay report for the batch you receive is available on request, and our full testing protocol is set out at Quality Standards.
How long does delivery take?
Orders are dispatched from South Africa, with timelines varying by region and courier. Current dispatch and transit windows are set out at Delivery Process.
Can I return an order?
Because these are laboratory compounds, returns are not accepted once an order has shipped. If your parcel arrives damaged, contact us within 48 hours with photographs of the packaging and product and we will arrange a replacement. The full terms are set out in our Refund Policy.
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