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Retatrutide

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.

01Inputs
03Evidence

What the evidence says

Cited human dosesRandomised trials

The published trials that established Retatrutide dosing are reported below, each with the paper it comes from. The structured range table — every range with its experience level, frequency and linked citation — lives in the Dosavy compound library.

04Facts

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.

05Warnings

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.

06Questions

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.

You worked out the draw. Now log this dose.

A calculator answers once and forgets. Dosavy keeps the concentration you mixed, the doses you actually took, and a reminder for the next one — with the same evidence labels you see on this page.