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Incretin (GLP-1 family)

Retatrutide

Retatrutide is an investigational once-weekly injection that acts on three hormone receptors: GIP, GLP-1 and glucagon. Phase 3 trials published in 2026 reported large weight loss, but it is not FDA-approved for any use.

  • Not FDA-approved
  • Human trials

Also known as LY3437943

Written by Upzo editorial team
Vial sizes
10 mg20 mg30 mg
Research supplier
Vial sizes
10 mg · 20 mg · 30 mg
10 mg + 2 mL
5,000 mcg/mL
Per U-100 unit
50 mcg
Studies in library
9
01

What is Retatrutide?

Retatrutide is a single synthetic peptide that activates three receptors: GIP and GLP-1, the two targets of tirzepatide, plus the receptor for glucagon. The idea behind adding glucagon activity is that, in animals, it raises energy expenditure on top of the appetite-lowering effect of the other two (Coskun 2022).

It was designed by Eli Lilly under the code LY3437943. Early human studies in 2022 established that it lasts long enough for once-weekly dosing (Urva 2022), phase 2 trials in obesity and type 2 diabetes followed in 2023, and the first phase 3 results (the TRANSCEND and TRIUMPH programmes) were published in 2026. All published trials were designed and funded by Eli Lilly.

Retatrutide has not been approved by the FDA or, as far as we could find, by any other major regulator. Anything sold today as "retatrutide" outside a clinical trial is not a licensed medicine, and the trial results below say nothing about what those products contain.

  • Type: synthetic peptide acting on three receptors (GIP, GLP-1 and glucagon).
  • Studied for: obesity, type 2 diabetes, fatty liver, knee osteoarthritis pain and sleep apnoea.
  • Strongest evidence: phase 3 randomised trials published in 2026, all run by the developer.
  • Legal status: investigational; not approved for any use.
02

Retatrutide protocols and supplies

Schedules reported for this peptide, with the syringe measure for each step and the supplies each one takes. Reported use is not evidence that a schedule works or is safe, and none of this is medical advice.

Phase 2 escalation

  • Subcutaneous injection, once a week
  • From clinical trials

The dose escalation used in published human trials, worked out for a research vial. Worked out with a 30 mg vial + 2 mL bacteriostatic water (15 mg/mL, 150 mcg per unit).

Amounts as reported, with the syringe or spray measure for the vial below. Not a recommendation.
PeriodAmount each timeU-100 unitsVolume
Weeks 1-42 mg13.30.13 mL
Weeks 5-84 mg26.70.27 mL
Weeks 9-128 mg53.30.53 mL
Week 13 on12 mg800.8 mL
Minimum supplies, worked out from the amounts above. Add a margin for losses.
Item12 weeks24 weeks
Injections1224
Total peptide56 mg200 mg
Retatrutide vials (30 mg)27
Bacteriostatic water4 mL14 mL
Water bottles (10 mL)12
U-100 insulin syringes1224
Alcohol swabs (boxes of 100)24 (1)48 (1)

Phase 3 escalation

  • Subcutaneous injection, once a week
  • From clinical trials

The dose escalation used in published human trials, worked out for a research vial. Worked out with a 30 mg vial + 2 mL bacteriostatic water (15 mg/mL, 150 mcg per unit).

Amounts as reported, with the syringe or spray measure for the vial below. Not a recommendation.
PeriodAmount each timeU-100 unitsVolume
Weeks 1-42 mg13.30.13 mL
Weeks 5-84 mg26.70.27 mL
Weeks 9-126 mg400.4 mL
Weeks 13-169 mg600.6 mL
Week 17 on12 mg800.8 mL
Minimum supplies, worked out from the amounts above. Add a margin for losses.
Item12 weeks24 weeks
Injections1224
Total peptide48 mg180 mg
Retatrutide vials (30 mg)26
Bacteriostatic water4 mL12 mL
Water bottles (10 mL)12
U-100 insulin syringes1224
Alcohol swabs (boxes of 100)24 (1)48 (1)
03

Retatrutide doses used in studies

The dose each published study gave its participants, copied from the paper. Not dosing instructions; animal doses do not convert directly to people.

At a glance: 9 studies report a dose (8 in people, 1 in animals).

Doses used in human studies

  • Jastreboff AM 2023: 1, 4, 8 or 12 mg once weekly (some arms with different starting doses) (Subcutaneous, once weekly; 48 weeks)
  • Urva S 2022: 0.5 mg, 1.5 mg, 3 mg, 3/6 mg or 3/6/9/12 mg (stepwise escalation) once weekly; comparators placebo or dulaglutide 1.5 mg (Subcutaneous, once weekly; 12 weeks)
  • Rosenstock J 2023: Maintenance doses of 0.5 mg, 4 mg, 8 mg or 12 mg once weekly (with different starting doses); comparators placebo or dulaglutide 1.5 mg (Subcutaneous, once weekly; 36 weeks)
  • Sanyal AJ 2024: 1 mg, 4 mg, 8 mg or 12 mg once weekly (Subcutaneous, once weekly; 48 weeks (primary endpoint at 24 weeks))
  • Bajaj HS 2026: 4 mg, 9 mg or 12 mg once weekly (Subcutaneous, once weekly; 40 weeks)
  • Jastreboff AM 2026: 4 mg, 9 mg or 12 mg once weekly (Subcutaneous, once weekly; 80 weeks)
  • Bellido V 2026: 4 mg, 9 mg or 12 mg once weekly (Subcutaneous, once weekly; 80 weeks)
  • Grunstein RR 2026: 4 mg, 9 mg or 12 mg once weekly (Subcutaneous, once weekly; 80 weeks)

Every study

Doses as reported by each study. Not a recommendation.
StudyDesignPopulationRouteDose usedDuration
Jastreboff AM 2023Randomised controlled trialhuman, n=338Subcutaneous, once weekly1, 4, 8 or 12 mg once weekly (some arms with different starting doses)48 weeks
Coskun T 2022Animal studymouse—Dose not given in the abstract; see the paper—
Urva S 2022Randomised controlled trialhuman, n=72Subcutaneous, once weekly0.5 mg, 1.5 mg, 3 mg, 3/6 mg or 3/6/9/12 mg (stepwise escalation) once weekly; comparators placebo or dulaglutide 1.5 mg12 weeks
Rosenstock J 2023Randomised controlled trialhuman, n=281Subcutaneous, once weeklyMaintenance doses of 0.5 mg, 4 mg, 8 mg or 12 mg once weekly (with different starting doses); comparators placebo or dulaglutide 1.5 mg36 weeks
Sanyal AJ 2024Randomised controlled trialhuman, n=98Subcutaneous, once weekly1 mg, 4 mg, 8 mg or 12 mg once weekly48 weeks (primary endpoint at 24 weeks)
Bajaj HS 2026Randomised controlled trialhuman, n=537Subcutaneous, once weekly4 mg, 9 mg or 12 mg once weekly40 weeks
Jastreboff AM 2026Randomised controlled trialhuman, n=2,339Subcutaneous, once weekly4 mg, 9 mg or 12 mg once weekly80 weeks
Bellido V 2026Randomised controlled trialhuman, n=1,152Subcutaneous, once weekly4 mg, 9 mg or 12 mg once weekly80 weeks
Grunstein RR 2026Randomised controlled trialhuman, n=691Subcutaneous, once weekly4 mg, 9 mg or 12 mg once weekly80 weeks
04

Evidence at a glance

What has been studied, by type of evidence. A result in animals or cells is a reason to study something in people, not proof that it works in people.

In humans

Summarised

Early and phase 2 trials

  • Phase 1b: in 72 people with type 2 diabetes over 12 weeks, the half-life was about 6 days and blood sugar and weight fell at the higher doses (Urva 2022).
  • Phase 2, obesity: in 338 adults without diabetes, weight change at 24 weeks ranged from 7.2% on 1 mg to 17.5% on 12 mg, against 1.6% on placebo, and kept falling through week 48 (Jastreboff 2023).
  • Phase 2, type 2 diabetes: HbA1c fell by up to about 2% and weight by up to about 17% at 36 weeks, more than with dulaglutide (Rosenstock 2023).
  • Liver fat: in a substudy of 98 people with fatty liver, liver fat on MRI fell by up to 82% at 24 weeks (Sanyal 2024).

Phase 3 trials (2026)

  • TRIUMPH-1: in 2,339 adults with obesity and no diabetes, mean weight change at 80 weeks was 17.6%, 23.7% and 25.0% on 4, 9 and 12 mg, against 3.9% on placebo. Knee osteoarthritis pain and sleep apnoea also improved in the subgroups with those conditions (Jastreboff 2026).
  • TRIUMPH-2: in 1,152 adults with obesity and type 2 diabetes, weight change at 80 weeks was 11.9% to 18.8% vs 5.1% on placebo (Bellido 2026).
  • TRANSCEND-T2D-1: in 537 adults with type 2 diabetes on diet and exercise alone, HbA1c fell by 1.69% to 1.94% vs 0.81% on placebo at 40 weeks (Bajaj 2026).
  • Sleep apnoea: in two trials nested in TRIUMPH-1 and TRIUMPH-2, breathing interruptions during sleep fell more than on placebo (Grunstein 2026).

Verdict: retatrutide now has phase 3 data from several double-blind, placebo-controlled trials, and the weight loss reported is among the largest seen in obesity drug trials. But the phase 3 papers are only months old, two were still online ahead of print when we checked, every trial was run by the developer, and there are no long-term safety or cardiovascular outcome results yet. Regulators have not yet reviewed the full data.

In animals

Summarised

Weight and energy use in mice

In obese mice, retatrutide lowered body weight and improved blood sugar control. The developers reported that its glucagon receptor activity increased energy expenditure, adding to the reduced food intake driven by its GIP and GLP-1 activity (Coskun 2022). We could not find independent animal studies from groups outside the developer.

In cells (in vitro)

Summarised

In cell assays, retatrutide activated the glucagon and GLP-1 receptors to a similar degree and the GIP receptor more strongly (Coskun 2022). How that balance translates to effects in the body is still being studied.

How much to trust each type of study

05

How Retatrutide may work

Proposed mechanisms from cell and animal studies. A plausible mechanism is not evidence of an effect in people.

Retatrutide is designed to act on three hormone receptors at once. The evidence for each comes from the developer's own studies:

  • GLP-1 and GIP receptors: in mice, activity at these receptors reduced food intake, and in people it lowered blood sugar in a dose-dependent way (Coskun 2022; Urva 2022).
  • Glucagon receptor: in mice, adding glucagon receptor activity increased energy expenditure (Coskun 2022). The large drop in liver fat in people may also involve this pathway, although in the liver substudy the fall in liver fat tracked weight loss (Sanyal 2024).
  • Long action: a half-life of about 6 days in people is what allows once-weekly injections (Urva 2022).
06

Reconstitution

How concentration changes with the amount of liquid added. A U-100 insulin syringe holds 1 mL in 100 units, so each unit is 0.01 mL. Step-by-step guide.

Step by step

  1. Wash your hands and work on a clean, uncluttered surface. Let a refrigerated vial reach room temperature so the stopper is easier to pierce.
  2. Wipe the rubber stopper of the peptide vial and of the bacteriostatic water with a fresh alcohol swab, and let them air-dry.
  3. Draw the chosen volume of bacteriostatic water into a sterile syringe. With 2 mL, a 10 mg vial ends up at 5,000 mcg/mL, or 50 mcg per U-100 unit.
  4. Insert the needle through the stopper and let the water run slowly down the inside wall of the vial, not straight onto the powder.
  5. Swirl or roll the vial gently until the powder dissolves. Do not shake it: foaming can damage some peptides.
  6. Check the solution against the light. It should be clear; cloudiness or particles mean something is wrong with the vial or the water.
  7. Write the date and the volume of water on the label. Every unit calculation later depends on that volume.
  8. Store the reconstituted Retatrutide vial in the refrigerator, away from light.

Concentration by volume

Concentration after adding the liquid, and how much peptide each U-100 unit (0.01 mL) holds.
VialLiquid addedConcentrationPer unit
10 mg1 mL10,000 mcg/mL100 mcg
10 mg2 mL5,000 mcg/mL50 mcg
10 mg3 mL3,333 mcg/mL33.3 mcg
20 mg1 mL20,000 mcg/mL200 mcg
20 mg2 mL10,000 mcg/mL100 mcg
20 mg3 mL6,667 mcg/mL66.7 mcg
30 mg1 mL30,000 mcg/mL300 mcg
30 mg2 mL15,000 mcg/mL150 mcg
30 mg3 mL10,000 mcg/mL100 mcg

Units per dose for each vial: 10 mg vial · 20 mg vial · 30 mg vial

Reconstitution calculator

Arithmetic only. It assumes the vial holds exactly what the label says.

Concentration
5,000 mcg/mL
Per U-100 unit
50 mcg
Volume for your amount
—
07

Measuring with a U-100 syringe

What each mark on an insulin syringe holds once the vial is mixed. This is arithmetic, not a dose.

Reading a U-100 syringe: how much peptide each mark holds in a 10 mg vial mixed with 2 mL. Not a dose.
Syringe markVolumePeptide in that volume
5 units0.05 mL250 mcg
10 units0.1 mL500 mcg
20 units0.2 mL1 mg
25 units0.25 mL1.25 mg
50 units0.5 mL2.5 mg
100 units1 mL5 mg
  • A U-100 insulin syringe holds 1 mL in 100 units, so each unit is 0.01 mL. The marks measure volume, not peptide.
  • Syringes come in 0.3 mL (30 units), 0.5 mL (50 units) and 1 mL (100 units) sizes. The smaller ones have finer marks and are easier to read for small volumes.
  • Read the volume at the top edge of the plunger's rubber seal, at eye level.
  • Tap out air bubbles before reading: a bubble takes up volume and makes the reading wrong.
  • Use a new sterile syringe and needle every time, and dispose of them in a sharps container.
08

Supplies

What reconstituting and measuring a vial takes.

  • The peptide vial, with its certificate of analysis (COA) for that batch. See how to read a COA.
  • Bacteriostatic water (water with 0.9% benzyl alcohol), which keeps a multi-use vial from growing bacteria. Sterile water has no preservative.
  • Sterile syringes to add the water, and U-100 insulin syringes to measure.
  • Alcohol swabs for the stoppers.
  • A sharps container for used needles.
  • A label or marker to write the date and the volume of water on the vial.
09

Side effects, safety and legal status

Because it is not approved, there is no prescribing information. In trials, the most common side effects were gastrointestinal (diarrhoea, nausea, vomiting, constipation), mostly mild to moderate and more frequent at higher doses. In TRIUMPH-2, diarrhoea affected 27-34% on retatrutide vs 13% on placebo, and nausea 14-28% vs 8% (Bellido 2026). Other points from the trials so far:

  • Low blood pressure and skin sensations: in TRIUMPH-2, hypotension (up to 6% vs under 1%) and dysaesthesia, an abnormal or unpleasant skin sensation (4-7% vs 1%), were more frequent on retatrutide (Bellido 2026).
  • Stopping because of side effects: 12% on 9 mg and 8% on 12 mg stopped because of adverse events or death in TRIUMPH-2, vs 5% on placebo. Deaths in that trial were judged unrelated to the drug by investigators (Bellido 2026).
  • Unknown long-term effects: the longest trials lasted 80 weeks. There are no published cardiovascular outcome trials, and rarer effects seen with related drugs (such as gallbladder or pancreas problems) cannot yet be ruled in or out.
  • Product quality: retatrutide sold online is not the investigational product used in trials. Its identity, dose, purity and sterility are unchecked, and any non-sterile injection carries a risk of infection.
FDA
Investigational. Not FDA-approved for any use. Eli Lilly has said it plans to file with the FDA in early 2027.
Status checked on
Oct 26, 2026
10

Storing Retatrutide

Before mixing

  • Freeze-dried (lyophilised) peptide is the most stable form. It is usually kept refrigerated, or frozen for long storage, sealed and away from light.
  • Heat, moisture and light speed up degradation. Keep the vial in its box and avoid leaving it in a car or by a window.

After mixing

  • Keep the reconstituted vial refrigerated and away from light. Do not freeze it again: freezing and thawing a solution can break the peptide down.
  • How long a mixed vial stays good depends on the peptide and the diluent, and for most research peptides there is no published stability data. Follow the supplier's guidance and discard any vial that turns cloudy.
  • Pierce the stopper as few times as possible, and always with a new sterile needle after wiping it with alcohol.
  • Write the volume of water on the label (for example "2 mL"). Without it, the unit calculations cannot be checked later.
11

Questions about Retatrutide

Is Retatrutide FDA-approved?

Investigational. Not FDA-approved for any use. Eli Lilly has said it plans to file with the FDA in early 2027.

What doses of Retatrutide have been studied?

Our library has 9 studies on Retatrutide. The doses each one used are in section 03, next to the study. They are not dosing instructions.

How much Retatrutide is in each syringe unit?

It depends on how much liquid is added to the vial. For a 10 mg vial with 2 mL, each U-100 unit holds 50 mcg. The reconstitution table and calculator work it out for other volumes.

Is retatrutide approved?

No. As of October 2026 it is investigational and not approved by the FDA for any use. Phase 3 results began to be published in 2026, and Eli Lilly has said it plans to file with the FDA in early 2027.

How is retatrutide different from tirzepatide and semaglutide?

Semaglutide acts on the GLP-1 receptor, tirzepatide on the GIP and GLP-1 receptors, and retatrutide on those two plus the glucagon receptor. We could not find a published trial comparing retatrutide directly with tirzepatide or semaglutide, so comparisons across separate trials should be read with caution.

Is research retatrutide the same as the drug in the trials?

No. The trials used product made by Eli Lilly under clinical-trial controls. Products sold online as research retatrutide are not made or checked to those standards, and their contents are unknown.

How much bacteriostatic water goes into a 10 mg Retatrutide vial?

There is no single correct volume: it only changes the concentration. For a 10 mg vial, 1 mL gives 10,000 mcg/mL, 2 mL gives 5,000 mcg/mL, 3 mL gives 3,333 mcg/mL. More water makes small amounts easier to measure; less water keeps volumes small. Whatever volume is used, write it on the label.

What does one unit on an insulin syringe mean?

On a U-100 syringe, 100 units = 1 mL, so one unit is 0.01 mL. How much peptide that holds depends on the concentration of the vial, which depends on how much water was added.

Can doses from animal studies of Retatrutide be converted to people?

No. Animal doses are reported per kilogram for a different species, and scaling them to people is not reliable. That is why Upzo shows each study dose next to its study, unconverted.

How should Retatrutide be stored?

Unopened freeze-dried vials are usually kept refrigerated and away from light. Once mixed, keep the vial refrigerated and follow the supplier's guidance on how long it lasts.

12

References

  1. Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. Jastreboff AM, Kaplan LM, Frías JP, et al. New England Journal of Medicine. 2023;389:514-526. doi:10.1056/NEJMoa2301972
  2. LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept. Coskun T, Urva S, Roell WC, et al. Cell Metabolism. 2022;34:1234-1247.e9. doi:10.1016/j.cmet.2022.07.013
  3. LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial. Urva S, Coskun T, Loh MT, et al. The Lancet. 2022;400:1869-1881. doi:10.1016/S0140-6736(22)02033-5
  4. 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. Rosenstock J, Frias J, Jastreboff AM, et al. The Lancet. 2023;402:529-544. doi:10.1016/S0140-6736(23)01053-X
  5. Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial. Sanyal AJ, Kaplan LM, Frias JP, et al. Nature Medicine. 2024;30:2037-2048. doi:10.1038/s41591-024-03018-2
  6. 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. Bajaj HS, Welch M, Shah P, et al. The Lancet. 2026;407:2402-2413. doi:10.1016/S0140-6736(26)00967-0
  7. Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity. Jastreboff AM, Kaplan LM, Davies MJ, et al. New England Journal of Medicine. 2026. doi:10.1056/NEJMoa2604169
  8. Retatrutide in adults with obesity and type 2 diabetes (TRIUMPH-2): a double-blind, parallel-group, randomised, placebo-controlled, phase 3 trial. Bellido V, le Roux CW, Ekinci EI, et al. The Lancet. 2026;408:1455-1472. doi:10.1016/S0140-6736(26)01861-1
  9. Retatrutide Once Weekly for Treatment of Obstructive Sleep Apnea. Grunstein RR, Somers VK, Azarbarzin A, et al. New England Journal of Medicine. 2026. doi:10.1056/NEJMoa2611477

Research supplier

For laboratory research use only.

Codex Research LabShips from Panama City · US domestic shipping

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Research and education only. Not medical advice. Many peptides on this site are not approved by the FDA for human use. Doses shown are the ones used in published studies and are not a recommendation. Talk to a licensed clinician before using any of them. Read the full disclaimer.