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Weight management

Retatrutide

The third generation of incretin research: a triple agonist that combines GLP-1, GIP and glucagon in one molecule.

5 min read 12 sources

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Still from the explainer video about this entry
Phase 3 · not approvedLab tested in the shop

No time to read it all? The video sums up the whole entry in about a minute, from how it works to the studies and storage.

Summary

At a glance

Sources checked on 25 Oct 2026

Targets
3 receptors

GLP-1, GIP and glucagon, each as an agonist according to ChEMBL12

Half-life
~6 days

Phase 1b study, fits one dose per week8

Body weight in phase 3
-25.0 %

TRIUMPH-1 at 80 weeks, highest study dose (placebo -3.9%)1

Liver fat
-82.4 %

relative change at 24 weeks, highest study dose (placebo +0.3%)7

Phase 3 in the registry
14 trials

5 of them completed, as of 25 Oct 202611

  • Retatrutide is a triple agonist: a single molecule that binds to the receptors for GLP-1, GIP and glucagon.1012
  • In phase 3 (TRIUMPH-1, 80 weeks) body weight fell by 25.0 percent on average at the highest study dose, by 3.9 percent on placebo.1
  • Further phase 3 results exist for type 2 diabetes and sleep apnoea. Large trials on heart, kidney and liver run until 2029 and 2030.23411
  • The most common effects in the trials were gastrointestinal. Heart rate also rose slightly in a dose-dependent way.25
  • Retatrutide is not approved (as of October 2026). Everything here is the state of research, not a recommendation.12
Profile

Updated May 2026

How long does it stay in the body?

Share left after one dose, calculated with a half-life of ~6 days

Half-life ~6 days
After 12 days: 25 %
Day 6 · 50 %Day 7, next dose · 45 %Day 12 · 25 %Day 18 · 12.5 %Day 30 · 3.1 %

Simplified model without an absorption phase, half-life from the TPD lexicon.

Class
Triple agonist

GLP-1 / GIP / glucagon

Frequency
Once weekly

subcutaneous

Half-life
~6 days
Form
Lyophilised powder

reconstituted with BAC water

Research status
Phase 3, not approved

as of October 2026

Sizes
5 to 60 mg

11 sizes in the shop

Contents 16 sections
  1. At a glance
  2. What is Retatrutide?
  3. How it works
  4. What you need
  5. Reconstitution
  6. Injection
  7. Dosing
  8. What the research shows
  9. Research status
  10. Side effects
  11. Lifestyle
  12. Storage
  13. Related compounds
  14. FAQ
  15. Glossary
  16. Sources

What is Retatrutide?

Retatrutide (development name LY3437943) is the third generation of incretin research. Where semaglutide hits one receptor and Tirzepatide two, Retatrutide acts on three at once: GLP-1, GIP and additionally glucagon. That third path, the glucagon receptor, is what is new about it and the reason Retatrutide is regarded, in research, as the most potent member of the class so far.

It is injected once a week and the half-life sits at roughly six days. Like the others it comes as a freeze-dried powder you dissolve in bacteriostatic water before the first use.

Comparison

One, two or three receptors

Which receptors each compound targets, as stated in the TPD lexicon. Tap a card to open its entry.

Mono agonist Semaglutide GLP-1 GIP Glucagon 1 of 3 receptors Dual agonist Tirzepatide GLP-1 GIP Glucagon 2 of 3 receptors Dual agonist Survodutide GLP-1 GIP Glucagon 2 of 3 receptors
Triple agonist Retatrutide GLP-1 GIP Glucagon 3 of 3 receptors

Simplified: more receptors does not automatically mean better, each path also brings its own effects. 1012

How it works

You know GLP-1 and GIP from Tirzepatide: they boost the insulin response, slow gastric emptying and dampen appetite. The glucagon receptor is the new addition in Retatrutide. Glucagon sounds counterintuitive at first because it can raise blood sugar, but in concert with the other two paths it mainly increases energy expenditure and fat breakdown, especially in the liver.

In studies this liver effect was particularly clear: liver fat dropped by over 80 percent at the higher doses. Studies suggest the three-path combination moves more on weight and metabolism than the earlier one- or two-receptor approaches.

Mechanism
  • GLP-1 Appetite dampened · Gastric emptying slowed
  • GIP Insulin response boosted
  • Glucagon Energy expenditure up · Fat breakdown, especially in the liver
Retatrutide binds as a triple agonist to three receptors: GLP-1, GIP and glucagon. Simplified diagram. Source: Coskun et al., Cell Metabolism 2022.

Where it acts

Three receptors, several organs

Tap a point or a card. Colour = receptor, grey = effect seen in trials.

  1. Brain

    Lower food intake, appetite dampened10

    GLP-1GIP
  2. Stomach

    Gastric emptying slowed9

    GLP-1
  3. Pancreas

    Blood sugar lowered, HbA1c clearly lower in trials6

    GLP-1GIP
  4. Liver

    Fat breakdown, liver fat dropped sharply in studies7

    Glucagon
  5. Energy balance

    Energy expenditure increased (shown in animal models)10

    Glucagon
  6. Heart

    Heart rate rose slightly, dose-dependent5

    Observed in trials

Targets in the ChEMBL database12

Compound CHEMBL5095485: three recorded mechanisms, all agonist with direct binding to the human receptor.

GLP-1 receptor
Gene
GLP1R
UniProt
P43220
ChEMBL
CHEMBL1784
Action
Agonist, direct binding
GIP receptor
Gene
GIPR
UniProt
P48546
ChEMBL
CHEMBL4383
Action
Agonist, direct binding
Glucagon receptor
Gene
GCGR
UniProt
P47871
ChEMBL
CHEMBL1985
Action
Agonist, direct binding

What you need

Before you start, have everything ready. The list is short:

Supplies

5 things, numbered as in the picture

Tick off what you already have. Vial and BAC water are our real shop photos at the same size.

Retatrutide vial and bacteriostatic water at the same size with the black TPD label, next to two U-100 insulin syringes, two alcohol swabs and a sharps container with a blue lid

  1. Retatrutide vial

    The Retatrutide vial with the freeze-dried powder

    In the shop

  2. Bacteriostatic water

    Bacteriostatic water to dissolve it

    In the shop

  3. U-100 insulin syringes

    U-100 insulin syringes for the injection (they also work for drawing the water, you just draw more often; a larger syringe is faster but not a must)

    Amazon (opens a new tab)

  4. Alcohol swabs

    Alcohol swabs for the vial cap and the skin

    Amazon (opens a new tab)

  5. Sharps container

    A sealable sharps container for used needles

As an Amazon associate we earn from qualifying purchases. Links open Amazon - no extra cost for you.

With everything clean and in one place, the rest is straightforward.

Reconstitution

The powder is dissolved in bacteriostatic water. How much water you add sets the concentration and therefore how many units you later draw on the insulin syringe for your dose.

That is exactly what the peptide calculator is for: pick your vial size and the water volume to instantly see the concentration and the units per dose. Roughly: less water means higher concentration and fewer units. For large vials from 30mg up, more water is worth it, otherwise the dose gets tiny and hard to read.

When dissolving, just add the bac water and let the powder dissolve. It does not matter if the water hits the powder directly. Swirling or shaking are both fine.

Step by step

Dissolving the powder

Four steps, the same for every vial size.

  1. 1Wipe the cap

    Clean the rubber stopper with an alcohol swab.

  2. 2Add BAC water

    Just add it, it does not matter if it hits the powder directly.

  3. 3Swirl or shake

    Until everything has dissolved, both are fine.

  4. 4Draw up

    With the U-100 insulin syringe.

Less water higher concentration fewer units on the syringe Example: 10 mg + 2 ml = 5 mg/ml

Injection

The injection is subcutaneous, into the fat layer under the skin. Common spots are the abdomen (keep about two finger-widths clear of the navel), the front and the inner side of the thigh, or the back of the upper arm.

The short version:

Injection

Where and at what angle

Pick a spot or switch the angle. Subcutaneous means: into the fat layer, not the muscle.

Rotate the spot each time, never the same one twice in a row.

90°More fat under the skin

Rule of thumb: where there is more fat under the skin, insert straight at 90 degrees. In lean people with little fat, 45 degrees, so the needle stays in the fat layer. Simplified diagram.

  1. Clean the spot with an alcohol swab and let it dry

  2. Pinch up a small fold of skin

  3. Insert the needle: at 90 degrees where there is more fat under the skin, at 45 degrees in lean people with little fat

  4. Inject slowly, wait a moment, then withdraw

  5. Put the needle straight into the sharps container

Rotate the site each time so the tissue does not get irritated. Never the same spot twice in a row.

Dosing

Dosing

Dosing, titration and syringe

Loading the dosing information …

  • Getting started and stepping up, drawn as a staircase
  • Units on the U-100 syringe for every step
  • How long one vial lasts
Retatrutide vial on light blue linen with an insulin syringe and a closed notebook
Symbolic image.

What the research shows

Retatrutide is still in clinical research. The first results from the phase 3 programme are now out. In the large TRIUMPH-1 trial (obesity without diabetes) body weight fell by 25.0 percent on average after 80 weeks at the highest study dose, by 3.9 percent on placebo. In TRIUMPH-2 with type 2 diabetes it was 18.8 versus 5.1 percent. In TRANSCEND-T2D-1 blood sugar (HbA1c) also dropped clearly in type 2 diabetes.

The phase 2 data were already clear: in the obesity study the highest dose (12mg) led to roughly 24 percent weight reduction at 48 weeks. In a liver substudy liver fat fell by over 80 percent at the higher doses. Further phase 3 trials on heart, kidney and liver run until 2029 and 2030.

The individual studies with links are in the source block below.

Study results

What the trials measured

Interactive: switch tabs, tap points, show or hide arms. Arms are named relative to each other, no dosing advice.

Body weight over 48 weeks5

Mean change in percent, phase 2 trial with 338 participants

0-5%-10%-15%-20%-25% Week 0Week 24Week 48 -2.1%-8.7%-17.1%-22.8%-24.2%

Placebo: Week 0 0.0%, Week 24 -1.6%, Week 48 -2.1%. Level 1 (lowest): Week 0 0.0%, Week 24 -7.2%, Week 48 -8.7%. Level 2: Week 0 0.0%, Week 24 -12.9%, Week 48 -17.1%. Level 3: Week 0 0.0%, Week 24 -17.3%, Week 48 -22.8%. Level 4 (highest, 12 mg): Week 0 0.0%, Week 24 -17.5%, Week 48 -24.2%.

Only the time points reported in the abstract are shown (weeks 0, 24 and 48), the lines connect them straight. Levels 2 and 3 each combine two groups with a different starting dose.

Body weight at the end of the trial123

Mean change in percent per trial

TRIUMPH-11 Obesity without diabetes, 80 weeks
Placebo -3.9%
Lowest study dose -17.6%
Middle study dose -23.7%
Highest study dose (12 mg) -25.0%
TRIUMPH-22 Obesity with type 2 diabetes, 80 weeks
Placebo -5.1%
Lowest study dose -11.9%
Middle study dose -16.8%
Highest study dose (12 mg) -18.8%
TRANSCEND-T2D-13 Type 2 diabetes, 40 weeks
Placebo -2.6%
Lowest study dose -11.5%
Middle study dose -13.9%
Highest study dose (12 mg) -15.3%

Values for all participants as randomised (treatment-regimen estimand), as stated in the abstracts. The trials differ in population and duration and are not directly comparable.

Liver fat at 24 weeks7

Relative change in liver fat, substudy with 98 participants (MASLD)

Phase 2 substudy7 Right: share with normal liver fat (below 5%)
Placebo +0.3% 0% normal
Level 1 (lowest) -42.9% 27% normal
Level 2 -57.0% 52% normal
Level 3 -81.4% 79% normal
Level 4 (highest, 12 mg) -82.4% 86% normal

Measured by MRI as the fat fraction of the liver. The substudy ran within the phase 2 obesity trial.

Research status

Where the research stands

From the first cell assays to the large phase 3 programme: every registered trial with status, participants and results. As of 25 Oct 2026. 11

  1. Preclinical Cell assays and mice
  2. Phase 1 15 trials, 14 completed
  3. Phase 2 3 trials, 3 completed
  4. Phase 3 14 trials, 5 completed
  5. Approval not yet
20,864 participants in phase 3 Planned figures for running trials Not approved yet. ChEMBL lists Retatrutide with phase 3 as the highest phase and no approval year.12
Show all 17 phase 2 and 3 trials on a timelineHide timeline 8 completed 9 running 5 with results
Phase 2
Phase 3

Bar: start to primary endpoint (planned for running trials). Green = completed, blue = progress until 25 Oct 2026. Phase 1: 15 trials on safety and pharmacokinetics, not shown as bars.

Side effects

Like the other incretins, the most common effects are gastrointestinal: nausea, fullness, sometimes diarrhoea or constipation, mainly at the start and after each dose increase. Through the glucagon path, studies additionally noted a slight rise in heart rate. In the phase 3 trial TRIUMPH-2 abnormal skin sensations (dysaesthesia) and low blood pressure also occurred more often than on placebo. These effects are dose-dependent and one more reason to ease in slowly and not go up too fast.

Tolerability

Frequency in TRIUMPH-2

Out of 100 participants per group, how many had the event over 80 weeks.

8 of 100 Placebo
14 of 100 Lowest study dose
21 of 100 Middle study dose
28 of 100 Highest study dose (12 mg)
Event PlaceboLowest study doseMiddle study doseHighest study dose (12 mg)
Nausea2 8%14%21%28%
Diarrhoea2 13%27%34%34%
Abnormal skin sensations (dysaesthesia)2 1%4%6%7%
Stopped due to side effects2 5%4%12%8%

Rounded values from the trial abstract (obesity with type 2 diabetes). In the phase 2 trial heart rate rose in a dose-dependent way, most around week 24, less afterwards.25

Lifestyle

Retatrutide takes the hunger away, the rest is on you. A few things get more out of the research phase and keep you healthy:

  1. Enough protein

    If you eat little, make the little you eat protein-rich, or you lose muscle along with fat.

  2. Drink enough

    With low appetite you often drink less without noticing. The risk of dehydration then goes up.

  3. Resistance training

    Keeps muscle mass while the weight comes off.

  4. Eat slowly

    With delayed gastric emptying you fill up faster, big portions sit heavy.

Plate with chicken, eggs and vegetables, yogurt, a glass of water and two blue dumbbells from above

Alcohol and very fatty meals make the nausea noticeably worse, especially early on.

Storage

The undissolved powder is robust, normal room temperature (around 20 to 25 degrees) is fine, ideally kept in the dark. Once dissolved, the solution goes into the fridge (2 to 8 degrees) and stays stable there for at least 4 to 6 months with barely any loss of potency. The bacteriostatic water brings a preservative that keeps the dissolved form stable for longer.

Shelf life

How long it keeps

Undissolved (powder) Room temperature, around 20 to 25 degrees, dark

Robust, no fridge needed. Keeps for several months without trouble.

Dissolved (mixed) Fridge, 2 to 8 degrees

At least 4 to 6 months with barely any loss of potency. The bacteriostatic water brings a preservative.

  • Keep it dark
  • Dissolved: 2 to 8 degrees
  • Note the mixing date on the vial
Vial with clear solution in the door of a bright fridge
Powder dark at room temperature, once dissolved into the fridge (2 to 8 degrees), stable there for at least 4 to 6 months. Symbolic image.
Level · Retatrutide

How the level builds up

One dose per week: each dose adds to what is left of the previous one.

Lexicon: Once weekly (subcutaneous)
Peak 1.8×Trough 0.8×
Day 21 · 4. dose
1.73× of the first dose
Plateau
from Day 21

96 % of the plateau after dose 4

Peak
1.8×

of the first dose

Trough
0.8×

before the next dose

Simplified model, values relative to the first dose, no dosing information. Dashed: the first dose alone, green: the plateau.

Related

Related compounds

Same receptors, blends with Retatrutide or a different path: all in the TPD lexicon.

Retatrutide
Tirzepatide Dual agonist, two of the three receptors Semaglutide GLP-1 only Mazdutide GLP-1 and glucagon Survodutide GLP-1 and glucagon Orforglipron GLP-1, studied as a tablet Cagrilintide Different path: amylin CagriSema (Cagri + Sema) Amylin plus GLP-1 Reta + Cagri Blend Contains Retatrutide plus cagrilintide Reta + Tesamorelin Blend Contains Retatrutide plus tesamorelin

FAQ

Common questions about Retatrutide

Short answers, each backed by the sources below.

Is Retatrutide approved?

No, as of 25 October 2026 there is no approval. Retatrutide is in phase 3: 14 phase 3 trials are listed on ClinicalTrials.gov, five of them completed. The first phase 3 results were published in 2026.1112

How does Retatrutide differ from Tirzepatide and Semaglutide?

The number of receptors. Semaglutide acts only on the GLP-1 receptor, Tirzepatide on GLP-1 and GIP. Retatrutide also targets the glucagon receptor. In animal models this added higher energy expenditure. A head-to-head trial against Tirzepatide is still running (TRIUMPH-5).1011

What did the phase 3 trials show?

In TRIUMPH-1 (obesity without diabetes) weight fell by 25.0 percent on average after 80 weeks at the highest study dose, by 3.9 percent on placebo. In TRIUMPH-2 (with type 2 diabetes) it was 18.8 versus 5.1 percent. In TRANSCEND-T2D-1 long-term blood sugar (HbA1c) fell by up to 1.94 percentage points in 40 weeks.123

How long does Retatrutide stay in the body?

The half-life was about six days in a phase 1b study. That fits one dose a week, which is how the trials give it. How the level builds up with weekly doses is shown in the level chart further down.8

What happens to liver fat?

In a substudy with fatty liver (MASLD) liver fat fell by about 81 to 82 percent after 24 weeks in the two higher levels. 86 percent reached normal liver fat below 5 percent at the highest level. A large phase 3 trial on liver disease runs until 2030.711

Which side effects were seen?

Most often gastrointestinal effects such as nausea and diarrhoea, depending on the dose. In TRIUMPH-2 abnormal skin sensations (dysaesthesia) and low blood pressure occurred more often than on placebo. In the phase 2 trial heart rate rose in a dose-dependent way, most around week 24.25

Which trials are still running?

Nine phase 3 trials are not finished yet. The largest: TRIUMPH-OUTCOMES on heart and kidney events with about 10,000 participants (planned end 2029) and SYNERGY-Outcomes on fatty liver (2030). The comparison with Tirzepatide (TRIUMPH-5) is due to reach its primary endpoint in November 2026.11

Glossary

Terms explained briefly

Dotted words in the text open these explanations directly.

Agonist
A substance that binds to a receptor and activates it, like the body's own messenger. A triple agonist activates three different receptors.
GIP
Glucose-dependent insulinotropic polypeptide: a second gut hormone that boosts insulin release when blood sugar is high.
GLP-1
Glucagon-like peptide 1: gut hormone that releases insulin, slows gastric emptying and signals fullness in the brain.
Glucagon
Pancreatic hormone. It can raise blood sugar and increases fat breakdown and energy use in the liver.
Half-life
Time after which only half of a substance is left in the blood. At about six days one dose a week keeps the level steady.
HbA1c
Long-term blood sugar: reflects average blood sugar over the past eight to twelve weeks.
Incretins
Gut hormones such as GLP-1 and GIP that are released after eating and boost the insulin response.
Lyophilisate
Freeze-dried powder. Without water a peptide keeps much longer.
MASLD
Metabolic dysfunction-associated steatotic liver disease, the fatty liver formerly mostly called NAFLD.
Placebo
Dummy preparation without active substance. Comparing against it shows what is due to the substance itself.
Receptor
Protein on the cell surface that a messenger docks onto. Only then does the cell respond.
Subcutaneous
Into the fat layer just under the skin.
Trial phases
Phase 1 tests tolerability in a few people, phase 2 looks for the dose, phase 3 confirms benefit and safety in thousands. After that, approval can be requested.

Evidence

Sources

Show all 12 sourcesHide sources 10 Studies1 Trial registry1 Database checked 25 Oct 2026

Studies

  1. Phase 3 trial TRIUMPH-1 in obesity

    Jastreboff et al., New England Journal of Medicine, 2026

    DOI 10.1056/NEJMoa2604169 PMID 42814954 NCT05929066
    Checked 25 Oct 2026 via doi.org, Crossref, PubMed
  2. Phase 3 trial TRIUMPH-2 in obesity with type 2 diabetes

    Bellido et al., The Lancet, 2026

    DOI 10.1016/S0140-6736(26)01861-1 PMID 42810372 NCT05929079
    Checked 25 Oct 2026 via doi.org, Crossref, PubMed
  3. Phase 3 trial TRANSCEND-T2D-1 in type 2 diabetes

    Bajaj et al., The Lancet, 2026

    DOI 10.1016/S0140-6736(26)00967-0 PMID 42250575 NCT06354660
    Checked 25 Oct 2026 via doi.org, Crossref, PubMed
  4. Phase 3 substudies on sleep apnoea

    Grunstein et al., New England Journal of Medicine, 2026

    DOI 10.1056/NEJMoa2611477 PMID 42904878
    Checked 25 Oct 2026 via doi.org, Crossref, PubMed
  5. Phase 2 study in obesity

    Jastreboff et al., New England Journal of Medicine, 2023

    DOI 10.1056/NEJMoa2301972 PMID 37366315 NCT04881760
    Checked 25 Oct 2026 via doi.org, Crossref, PubMed
  6. Phase 2 study in type 2 diabetes

    Rosenstock et al., The Lancet, 2023

    DOI 10.1016/S0140-6736(23)01053-X PMID 37385280 NCT04867785
    Checked 25 Oct 2026 via doi.org, Crossref, PubMed
  7. Phase 2a substudy on liver fat (MASLD)

    Sanyal et al., Nature Medicine, 2024

    DOI 10.1038/s41591-024-03018-2 PMID 38858523
    Checked 25 Oct 2026 via doi.org, Crossref, PubMed
  8. Phase 1b study in type 2 diabetes

    Urva et al., The Lancet, 2022

    DOI 10.1016/S0140-6736(22)02033-5 PMID 36354040 NCT04143802
    Checked 25 Oct 2026 via doi.org, Crossref, PubMed
  9. Study on gastric emptying

    Urva et al., Diabetes, Obesity and Metabolism, 2023

    DOI 10.1111/dom.15167 PMID 37311727
    Checked 25 Oct 2026 via doi.org, Crossref, PubMed
  10. Discovery and pharmacology of the triple agonist

    Coskun et al., Cell Metabolism, 2022

    DOI 10.1016/j.cmet.2022.07.013 PMID 35985340
    Checked 25 Oct 2026 via doi.org, Crossref, PubMed

Trial registry

  1. All trials on ClinicalTrials.gov

    ClinicalTrials.gov, U.S. National Library of Medicine

    Checked 25 Oct 2026 via ClinicalTrials.gov API v2

Database

  1. Mechanism and targets in ChEMBL

    ChEMBL, EMBL-EBI (CHEMBL5095485)

    Checked 25 Oct 2026 via ChEMBL

In the shop

Retatrutide in the catalog

Sizes, prices and shipping times are on the product page.

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