Retatrutide Reconstitution Calculator
Retatrutide (Eli Lilly's LY3437943) is a single synthetic peptide that agonises three receptors at once: GIP, GLP-1 and glucagon. The GIP and GLP-1 arms work as tirzepatide's do; the glucagon arm is the addition, intended to raise energy expenditure and mobilise hepatic fat. Fatty-acid modification gives albumin binding and a mean half-life of about 6 days, which is why every published trial dosed it once weekly by subcutaneous injection. It is investigational: not approved by the FDA, the EMA or Swissmedic for any indication, so there is no approved presentation and no manufacturer mixing instruction. This calculator converts a vial size and a mixing volume into mg/ml and syringe units.
Curated by Dosavy from published literature and regulator labels. Published 1 September 2026, last reviewed 5 September 2026. No clinician reviews this page.
Enter a target dose above to see the draw.
What the evidence says
| Experience | Route | Range | Frequency |
|---|---|---|---|
| Beginner | Subcutaneous | 1–2 mg[1][2]Trial initiation range, not a maintenance target. In the phase 2 obesity trial the escalating arms began at an initial dose of 2 mg once weekly before stepping up to 4, 8 or 12 mg, and 1 mg once weekly was itself studied as a full 48-week maintenance arm. It produced a mean weight change of -8.7% at 48 weeks, versus -2.1% for placebo. The phase 2 type 2 diabetes trial went lower still, with a 0.5 mg once-weekly maintenance arm. These are protocol doses from registered trials, not a licensed starting regimen. | Once weekly |
| Intermediate | Subcutaneous | 4–8 mg[1][3]The mid maintenance doses studied across both phase 2 programmes and carried into phase 3. Reached by stepwise escalation from a 2 mg or 4 mg initial dose, not started at. In the phase 2 obesity trial mean weight change at 48 weeks was -17.1% in the combined 4 mg group and -22.8% in the combined 8 mg group, versus -2.1% for placebo; in the phase 3 type 2 diabetes monotherapy trial, 4 mg once weekly lowered HbA1c by 1.69 percentage points over 40 weeks. | Once weekly |
| Advanced | Subcutaneous | 9–12 mg[1][3]The highest doses studied in humans in the published trials. 12 mg once weekly was the top phase 2 arm in both obesity and type 2 diabetes; the phase 3 monotherapy trial used 4 mg, 9 mg and 12 mg. In the phase 2 obesity trial the 12 mg arm reached the target dose from a 2 mg initial dose and produced a mean weight change of -24.2% at 48 weeks. No published trial in this packet administered more than 12 mg once weekly, so there is no human evidence of any kind above that dose. | Once weekly |
- BeginnerSubcutaneous
Once weekly
Trial initiation range, not a maintenance target. In the phase 2 obesity trial the escalating arms began at an initial dose of 2 mg once weekly before stepping up to 4, 8 or 12 mg, and 1 mg once weekly was itself studied as a full 48-week maintenance arm. It produced a mean weight change of -8.7% at 48 weeks, versus -2.1% for placebo. The phase 2 type 2 diabetes trial went lower still, with a 0.5 mg once-weekly maintenance arm. These are protocol doses from registered trials, not a licensed starting regimen.
- IntermediateSubcutaneous
Once weekly
The mid maintenance doses studied across both phase 2 programmes and carried into phase 3. Reached by stepwise escalation from a 2 mg or 4 mg initial dose, not started at. In the phase 2 obesity trial mean weight change at 48 weeks was -17.1% in the combined 4 mg group and -22.8% in the combined 8 mg group, versus -2.1% for placebo; in the phase 3 type 2 diabetes monotherapy trial, 4 mg once weekly lowered HbA1c by 1.69 percentage points over 40 weeks.
- AdvancedSubcutaneous
Once weekly
The highest doses studied in humans in the published trials. 12 mg once weekly was the top phase 2 arm in both obesity and type 2 diabetes; the phase 3 monotherapy trial used 4 mg, 9 mg and 12 mg. In the phase 2 obesity trial the 12 mg arm reached the target dose from a 2 mg initial dose and produced a mean weight change of -24.2% at 48 weeks. No published trial in this packet administered more than 12 mg once weekly, so there is no human evidence of any kind above that dose.
Published ranges, reported as the literature states them and numbered to the sources at the foot of this page. Not a recommendation.
Retatrutide at a glance
- Category
- GLP-1
- Half-life
- 6 d
- Routes
- Subcutaneous
- Regulatory status
- Not approved
- Also sold as
- LY3437943, triple agonist, GIP/GLP-1/glucagon receptor triagonist, triple-hormone-receptor agonist
Mechanism
A single synthetic peptide with agonist activity at three receptors: the glucose-dependent insulinotropic polypeptide (GIP) receptor, the GLP-1 receptor, and the glucagon receptor. The GIP and GLP-1 arms drive glucose-dependent insulin secretion, appetite suppression and delayed gastric emptying in the same way as tirzepatide; the added glucagon receptor arm is intended to raise energy expenditure and mobilise hepatic fat, which is the mechanistic reason the compound produces larger liver-fat reductions than GLP-1-only agents. Fatty-acid modification gives albumin binding and a mean half-life of approximately 6 days, supporting once-weekly subcutaneous dosing.
Reconstitution
There is no approved presentation and no published reconstitution instruction. Trial drug was administered as a subcutaneous injection prepared by the sponsor. Any lyophilised powder sold as 'retatrutide' has an unverified identity, purity and peptide content, so the milligram figures from the trials below cannot be assumed to describe what is actually in such a vial.
Storage
No approved product and therefore no manufacturer storage instructions exist. Trial material was supplied as a solution for subcutaneous injection under sponsor-controlled conditions; nothing published in this packet establishes stability conditions for material obtained outside a trial.
Frequency in practice
Once weekly by subcutaneous injection in all published trials, with a multi-week dose-escalation period before the target dose.
Regulatory
Investigational. Retatrutide (LY3437943, Eli Lilly) is not approved by the FDA, the EMA or Swissmedic for any indication. It has completed phase 2 trials in obesity, type 2 diabetes and MASLD and has published phase 3 results (TRANSCEND-T2D-1), with further phase 3 cardiovascular, kidney and obesity trials ongoing. It is widely sold on the grey market as a 'research chemical'; that material is not the trial drug and is not regulated as a medicine.
What to know before anything else
Not approved for human use anywhere. There is no prescribing information, so there is no boxed warning, no contraindication list, no drug-interaction table and no approved maximum dose. The doses below are trial protocol doses, not a licensed regimen.
Material sold as 'retatrutide' outside a clinical trial is not the trial drug. Identity, purity, peptide content and sterility are unverified, so a stated milligram figure on such a vial cannot be assumed to correspond to the trial doses.
Gastrointestinal adverse events were the most common adverse events in every trial and were clearly dose-related; the trials mitigated them with multi-week dose escalation, which is why the escalation schedule is part of the dosing information rather than optional.
Every FDA-approved GLP-1 receptor agonist carries a boxed warning for rodent thyroid C-cell tumors and is contraindicated with a personal or family history of medullary thyroid carcinoma or MEN 2. No regulator has publicly adjudicated whether that class warning applies to retatrutide; the absence of a warning is an absence of assessment, not an all-clear.
Glucagon receptor agonism is not shared with semaglutide or tirzepatide. It increases hepatic glucose output and energy expenditure, and its long-term consequences for glycaemic control, heart rate, liver enzymes and body composition are still being characterised in ongoing phase 3 trials.
Combining an investigational incretin agonist with an approved GLP-1 or GIP/GLP-1 agonist has not been studied at all. Approved labels in this class explicitly advise against concomitant use of two GLP-1 receptor agonists.
The published trials excluded groups routinely present in real use: the obesity trial enrolled adults with BMI ≥30 (or ≥27 with a weight-related condition), and there are no published pregnancy, lactation, paediatric or hepatic-failure data.
Reviewed interactions
These are the pairs Dosavy holds reviewed, cited data on. A combination that is not listed here has not been assessed, which is not the same as being safe.
- Dangerouswith Semaglutide
Do not combine. Semaglutide's label states that coadministration with any other GLP-1 receptor agonist is not recommended, and retatrutide's GLP-1 arm makes it exactly that. Retatrutide has no approved label at all, so there is no maximum dose to reason from on that side. The shared gastrointestinal effects (nausea, vomiting, diarrhoea, dehydration) are the dose-limiting toxicity of the class.[4]
Retatrutide agonises the GIP, GLP-1 and glucagon receptors; semaglutide agonises the GLP-1 receptor. The overlapping GLP-1 agonism is duplicative.
- Dangerouswith Survodutide
Do not combine. Both are GLP-1 receptor agonists (retatrutide as one of three targets, survodutide as one of two), and the approved members of this class carry explicit label instructions against combining any two GLP-1 receptor agonists. Neither of these two has an approved label, so nothing defines a safe combined dose, and both also agonise the glucagon receptor, which is duplicated as well.[4][5]
Overlapping agonism at both the GLP-1 and glucagon receptors. Duplicated GLP-1 activity compounds gastrointestinal and volume-depletion effects; duplicated glucagon activity compounds the heart-rate and hepatic-metabolism effects that arm produces.
- Dangerouswith Tirzepatide
Do not combine. Tirzepatide's label states that coadministration with any GLP-1 receptor agonist is not recommended, and retatrutide is one. The two also share GIP-receptor agonism, so the overlap is at two of three targets. This is closer to doubling a dose of the same drug than to combining two different ones.[5]
Both agonise the GIP and GLP-1 receptors; retatrutide adds glucagon-receptor agonism. Duplicated GIP and GLP-1 activity compounds the class's gastrointestinal adverse effects.
Retatrutide questions
What doses of retatrutide have actually been given to people?
Only in registered trials, and only once weekly by subcutaneous injection. The phase 2 obesity trial published in the New England Journal of Medicine (PMID 37366315, 338 participants, 48 weeks) studied 1 mg, 4 mg, 8 mg and 12 mg maintenance arms; the phase 2 type 2 diabetes trial in the Lancet (PMID 37385280, 281 participants) went as low as 0.5 mg; and the phase 3 TRANSCEND-T2D-1 trial in the Lancet (PMID 42250575, 537 participants, 40 weeks) used 4 mg, 9 mg and 12 mg. Those are protocol doses, not a licensed regimen.
Is 12 mg once weekly a ceiling?
It is the highest dose any published retatrutide trial administered. Twelve milligrams once weekly was the top arm in both phase 2 programmes and in the phase 3 TRANSCEND-T2D-1 monotherapy trial (PMID 42250575), where it produced an HbA1c change of -1.94 percentage points and a mean bodyweight change of -15.3% over 40 weeks. Above 12 mg once weekly there is no human evidence of any kind: not a safety signal, not a null result, nothing. That is an absence of data, not a demonstration that higher is tolerable.
Why do the trials escalate the dose over several weeks?
Because gastrointestinal adverse events were the most common adverse events in every retatrutide trial and were clearly dose-related. The trials mitigated them with multi-week escalation, which is why the escalation schedule is part of the dosing information rather than an optional refinement. In the phase 2 obesity trial (PMID 37366315) the 12 mg arm was reached from a 2 mg initial dose, and the 4 mg and 8 mg arms from 2 mg or 4 mg initial doses; nobody in those trials started at their maintenance dose.
How does retatrutide differ from semaglutide and tirzepatide?
By the glucagon receptor. Semaglutide hits GLP-1; tirzepatide hits GIP and GLP-1; retatrutide adds glucagon-receptor agonism to both of those. That third arm increases hepatic glucose output and energy expenditure, and it is the mechanistic reason retatrutide produces larger liver-fat reductions than GLP-1-only agents. Its long-term consequences for glycaemic control, heart rate, liver enzymes and body composition are still being characterised in ongoing phase 3 trials, so the extra receptor is also the part of the profile with the least follow-up behind it. Approved labels in the class point the same way: Wegovy's FDA prescribing information advises against coadministering any other GLP-1 receptor agonist and Zepbound's says the same, and retatrutide is one.
Does a vial sold as 'retatrutide' contain what the trials used?
There is no basis to assume so. Trial drug was a solution for subcutaneous injection prepared under sponsor-controlled conditions; retatrutide sold on the grey market as a 'research chemical' is not that drug and is not regulated as a medicine. Its identity, purity and sterility are unverified, so a milligram printed on such a vial cannot be assumed to match a milligram from a published trial arm.
How should retatrutide be stored, and how is it reconstituted?
No approved product exists, so there are no manufacturer storage instructions and no published reconstitution instruction: nothing establishes stability conditions for material obtained outside a trial. What the calculator above does is arithmetic, not guidance: the vial holds a fixed mass and the bacteriostatic water sets the concentration. A 10 mg vial mixed with 2 ml gives 5 mg/ml, so 0.1 ml on the barrel is 500 mcg; the same vial mixed with 5 ml gives 2 mg/ml and that same 0.1 ml is 200 mcg.
Does the thyroid C-cell boxed warning apply to retatrutide?
Nobody has said. Every FDA-approved GLP-1 receptor agonist carries a boxed warning for rodent thyroid C-cell tumours and is contraindicated with a personal or family history of medullary thyroid carcinoma or MEN 2. No regulator has adjudicated whether that class warning extends to retatrutide, and with no prescribing information there is no boxed warning and no contraindication list to consult. That is an absence of assessment, not an all-clear.
Every number above, and where it came from
5 sources, numbered where they are used. Each one links to the paper or the label itself, not to a summary of it.
- [1]Triple-Hormone-Receptor Agonist Retatrutide for Obesity: A Phase 2 Trial
The New England Journal of Medicine · 2023 · Phase 2 randomised, double-blind, placebo-controlled trial · n=338
- [2]Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial conducted in the USA
Lancet · 2023 · Phase 2 randomised, double-blind, placebo- and active-controlled trial · n=281
- [3]Efficacy and safety of retatrutide, a GIP, GLP-1, and glucagon receptor agonist, in people with type 2 diabetes and inadequate glycaemic control with diet and exercise (TRANSCEND-T2D-1): a double-blind, randomised, phase 3 trial
Lancet · 2026 · Phase 3 randomised, double-blind, placebo-controlled trial · n=537
- [4]WEGOVY (semaglutide) injection, for subcutaneous use: FDA prescribing information
2024 · FDA approved label
- [5]ZEPBOUND (tirzepatide) injection, for subcutaneous use: FDA prescribing information
2026 · FDA approved label
The rest of the math
- Reconstitution calculatorVial size and diluent to mg/mL and syringe units, with barrel sizes and IU conversion.
- Vial longevityHow many doses a vial holds and the date it runs out.
- Cost per doseVial price against doses drawn, so two vial sizes can be compared honestly.
- Half-life and decayFirst-order clearance, time to steady state, and what remains at a given hour.
- GLP-1 titration scheduleEscalation steps and week-by-week timing for GLP-1 receptor agonists.
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A calculator answers once and forgets. Dosavy keeps the schedule you set, the doses you actually took, and the reminder for the next one, with the same evidence labels you see on this page.