Retatrutide
LY3437943GGG tri-agonistGLP-3Evidence
Early human
Half-life
6 d
Typical vial
5 mg
Route
Subcut
What it is
An investigational once-weekly triple agonist acting on the GLP-1, GIP and glucagon receptors. Not approved anywhere.
Retatrutide adds a third target to the dual-agonist approach: alongside GLP-1 and GIP it activates the glucagon receptor. The rationale is that glucagon receptor activity increases energy expenditure, so the compound would both reduce intake and raise output.
Published phase 2 results reported the largest average weight reductions yet seen in a trial of this class. That result is genuinely notable and genuinely preliminary. Phase 2 establishes a signal — not a safety profile — and retatrutide has completed no phase 3 programme and holds no approval anywhere. It is the clearest case on this site of a compound with real evidence behind it that is nonetheless still investigational.
How it works
The GLP-1 and GIP components work as they do in tirzepatide: incretin signalling that reduces appetite and improves how the body handles glucose after eating.
Glucagon receptor agonism is the addition. Glucagon raises hepatic glucose output, normally the opposite of what a diabetes drug wants. It also increases resting energy expenditure and promotes fat breakdown in the liver. Balancing the three activities so the metabolic benefit outweighs the effect on blood glucose is the central design problem of this compound class.
What it is studied for
Each entry states the evidence behind it. We do not rank indications by effectiveness — for most compounds here, that would be a claim nobody can support.
Weight management
Clinical trialThe primary endpoint of the published phase 2 trial.
EvidenceOne randomised placebo-controlled phase 2 trial over 48 weeks. No phase 3 results published.
Regulatory status
Last reviewed 12 Aug 2026. Positions in this category change frequently, so we date the line.
Investigational. Not approved for human use in any jurisdiction. Sold only as a research chemical, with no manufacturing standard behind that label.
- A GLP-1 ingredient maker was stopped at the border. The vendors we index were never eligible to be.
- Orforglipron is approved, and it is not a peptide. Both halves matter.
- GLP-1, GLP-2 and GLP-3 on a vendor listing are not what they sound like
- Retatrutide: what the phase 3 programme does and does not settle
- GLP-1 compounds: the gap between the trials and the vial
Identity and clearance
What the molecule is, and how long a dose stays measurable.
Molecule
- Class
- Triple GLP-1, GIP and glucagon receptor agonist
- Length
- 39 amino acids
A single engineered peptide with a fatty acid chain for albumin binding, in the same structural family as tirzepatide.
Pharmacokinetics
Clinical trialAbout six days, supporting weekly dosing.
Dose protocols reported in sources
Displayed for reference only. Every row says where it came from, and a trial protocol and a community convention are not the same kind of information. None of this is fed into the calculator, and none of it is a recommendation.
A week-by-week progression is also reported for Retatrutide. See it against a 5 mg vial, where the syringe units can be worked out.
| Goal | Dose | Frequency | Route | Units, 5 mg vial | Source | Start this protocol |
|---|---|---|---|---|---|---|
| Phase 2 starting dose | 2 mg | Once weekly | Subcutaneous | 40 u | Clinical trial | Start this |
| Phase 2 escalation and maintenance arms | 4 mg – 12 mg | Once weekly, escalated in steps | SubcutaneousThe trial ran 1, 4, 8 and 12 mg maintenance arms with differing escalation schedules. | from 80 u | Clinical trial | Start this |
The doses above in syringe units, for the vial you have:
Start this copies a row into a protocol of your own, which you can then edit. Where a source gave a dose range or an ambiguous frequency, those fields arrive empty — we will not pick a number on your behalf.
Work out what to draw
Pre-filled with a 10 mg vial as a worked example. These are not recommended values — change them to match the vial in front of you.
Draw to 40 units on a 1 mL U-100 syringe. That is 0.4 mL, containing 2 mg of Retatrutide.
40 units sits exactly on a printed line.
BioAlmanac performs arithmetic on values you enter. It does not recommend doses, schedules or compounds, and nothing here is medical advice. Confirm every calculation against your vial and syringe before drawing, and speak with a licensed healthcare provider.
Open this calculation in the full calculator
Units, concentration, bacteriostatic water — the glossary defines the vocabulary, and a unit is not a fixed volume.
Safety
Reported effects, the situations that need care, and the ones that mean stop.
Reported effects
- Nausea, vomiting, diarrhoeaClinical trial
Very common in the phase 2 trial
Dose-related, as with the rest of this class.
- Increased heart rateClinical trial
Observed in the phase 2 trial
A plausible consequence of glucagon receptor agonism, and one of the reasons longer-term safety data matters for this compound specifically.
- Reduced appetiteClinical trial
Very common
- Longer-term safetyClinical trial
Unknown
Phase 2 establishes a signal over 48 weeks in a few hundred people. It does not establish a safety profile.
When to stop
- Severe, persistent abdominal pain radiating to the back. Seek urgent medical care.
- Persistent vomiting or inability to keep fluids down.
- A sustained rise in resting heart rate, palpitations, or chest pain.
- Any allergic response: rash, hives, facial swelling, or difficulty breathing. Seek urgent care.
- If you become pregnant or are planning to.
Interactions and situations that need care
- Personal or family history of medullary thyroid carcinoma, or MEN 2Avoid
The class carries this warning, and retatrutide has no completed long-term safety programme of its own.
- Existing cardiac arrhythmia or uncontrolled hypertensionUse caution
Heart rate increases were observed in the phase 2 trial. In someone with an existing cardiac problem that is a meaningful unknown rather than a theoretical one.
- History of pancreatitisUse caution
Consistent with the rest of the incretin class.
- Pregnancy and breastfeedingAvoid
No reproductive safety data, and an investigational compound.
- Planned surgery or general anaesthesiaUse caution
Delayed gastric emptying is an aspiration risk under anaesthesia. Tell your anaesthetist.
What to expect
What the sources describe over time, and how confident anyone can be about it.
- In the phase 2 trial, mean weight reduction at 48 weeks was about 24% in the 12 mg arm, the largest reported for this class to date.
- That figure comes from one phase 2 trial in a few hundred people. It is a signal worth taking seriously and it is not the same as a completed phase 3 programme.
- Gastrointestinal effects and heart rate increases were both dose-related.
- There is no long-term safety data. That is the single most important thing to weigh about this compound.
Storage and combinations
How to keep it, and what it does and does not go with.
Storage and handling
- Freeze-dried powder
- Refrigerated at 2–8 °C, protected from light and moisture.
- After mixing
- Refrigerated at 2–8 °C. Do not freeze.
- Long-term, frozen
- Unopened lyophilised powder is stable at −20 °C or colder.
With other peptides
- Tirzepatideincompatible
Overlapping GLP-1 and GIP agonism. These are alternatives, not a stack.
- Semaglutideincompatible
Overlapping GLP-1 agonism. These are alternatives, not a stack.
Stacks with Retatrutide in them
Documented combinations and plans people have published, with full schedules.
Documented combinations, with full schedules.
Checking your vial
Research chemicals carry no manufacturing standard, so what the vial looks like is often the only quality signal available before you use it.
White cake, clear solution
Standard for this class.
Collapsed cake or cloudy solution
Indicates heat damage or degradation.
Vocabulary on this page
- Titration
- Raising a dose in planned steps rather than starting at the target, so side effects appear at a dose small enough to retreat from.
- Lyophilised
- Freeze-dried. The process used to turn a peptide solution into a stable dry powder for shipping and storage.
- GLP-1 agonist
- A drug acting on the receptor for glucagon-like peptide-1, a gut hormone that signals fullness and slows stomach emptying.
- Research chemical
- A legal label, not a quality grade. It describes what a seller is permitted to sell you, and says nothing about what is in the vial.
- Stack
- Several separate compounds run at the same time, each in its own vial and on its own schedule.
- Protocol
- One compound, with a dose, a frequency and a length: the plan, as opposed to what was actually taken.
Questions
- Is retatrutide approved?
- No. It is investigational, has published phase 2 results, and holds no approval in any jurisdiction. Anything sold under this name is a research chemical.
- Why is it called a triple agonist?
- It activates three receptors, GLP-1, GIP and glucagon, where semaglutide acts on one and tirzepatide on two.
- Why does heart rate come up with retatrutide specifically?
- Glucagon receptor activity is the third mechanism, and increases in heart rate were observed in the phase 2 trial. For someone with an existing cardiac condition that is the most relevant difference from the dual agonists.
References
Everything on this page that came from a source, with the source.
Triple-Hormone-Receptor Agonist Retatrutide for Obesity: A Phase 2 Trial
New England Journal of Medicine, 2023 · Randomised, double-blind, placebo-controlled phase 2 trial
Adults with obesity · n = 338 · 1, 4, 8 or 12 mg once weekly · 48 weeks
Mean weight reduction of about 24% in the 12 mg arm at 48 weeks. Gastrointestinal adverse events were dose-related, and heart rate increases were observed.
10.1056/NEJMoa2301972
Compiled community protocols
BioAlmanac editorial summary of a public protocol compilation, 2026 · Not a study
Records a week-by-week progression described on a vendor-adjacent protocol site, retrieved August 2026. Only the doses are taken from it. Its own syringe-unit conversions were checked against the vial sizes it states and several understate the volume by half, so nothing computed by that source is reproduced here — the units on this site are worked out from the vial in front of you. Carries no evidential weight about safety or effect.
Retatrutide compared with
Retatrutide vs semaglutide
One receptor against three, and a finished approval against a trial programme still running. The largest reported effect in the class, set beside the most established one.
Tirzepatide vs retatrutide
Two and three receptors respectively. Retatrutide reported the larger weight reduction; tirzepatide has a completed phase 3 programme and an approval. This is a different kind of claim.
Also compared with Liraglutide, Cagrilintide, Orforglipron, Mazdutide, Survodutide, Eloralintide.
Related compounds
Tirzepatide
A once-weekly dual agonist that activates both the GIP and GLP-1 receptors, approved for type 2 diabetes and for weight management.
Semaglutide
A long-acting GLP-1 receptor agonist approved for type 2 diabetes and for weight management, dosed once weekly.
Liraglutide
The first GLP-1 analogue approved for weight loss. A daily injection, superseded by weekly semaglutide but still the best-documented compound in the class.
Cagrilintide
A long-acting amylin analogue in late-stage trials. It works on a different satiety pathway from the GLP-1 drugs. Which is why it is being developed alongside semaglutide rather than against it.
Next
What to do with Retatrutide
- Keep a record of itTurn a dose and a schedule into a protocol, then log what you actually take. Retatrutide is filled in for you.
- See what it costsPer-milligram prices read from vendor sites and confirmed by a person, so vial sizes compare.
- Check a combinationWhat our profiles record about Retatrutide alongside each other compound — including the pairs where nothing is recorded.
Keep this page honest
If something here is wrong, out of date, or missing a source, tell us and we will fix it and say that we did.
This page is educational. It describes what published research reports, not what you should do. Peptides discussed here are largely not approved for human use, and nothing on BioAlmanac is medical advice. No clinician reviews these pages.
Page last updated 12 Aug 2026