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Retatrutide

Experimental drug for major weight loss

Eli Lilly’s experimental “triple agonist”

Match every finding to its exact substance, formulation, route and study population. A related molecule or approved medicine does not validate a catalog vial.

Human / product-specific records · Unresolved sources
Explore the evidenceWhy people take it
Compare this compoundRead original sources Community reports
Schematic illustration · View structure evidence

Simplified drawing of a chain of 39 amino acids, with its fatty-acid tail

At a glance

Why people take it. And what backs it up.

  1. Lose a lot of weight

    Proven in large trials, not approved

    Many buy unapproved research vials hoping for big weight loss; in a large trial, adults with obesity lost 25% on the top dose.

    Sources (4)

  2. Break a weight-loss stall

    People report it, not studied

    People stalled on tirzepatide switch to it or add it on top, hoping its extra hormone target restarts weight loss.

    Sources (2)

  3. Keep weight off

    People report it, not studied

    Once at goal, some drop to small weekly or every-other-week doses, hoping to hold their weight and keep food noise quiet.

    Sources (2)

  4. Cut liver fat

    Early human studies

    Some take it to clear fatty liver; in a trial, most people on higher doses reached normal liver fat within six months.

    Sources (3)

  5. Lower blood sugar

    Proven in large trials, not approved

    People with diabetes take it to lower blood sugar; in a large trial, A1c fell nearly 2 points, versus under 1 on placebo.

    Sources (3)

Evidence briefing

Sources checked

What the sources support.

Retatrutide (LY3437943) is an investigational GIP/GLP-1/glucagon receptor agonist. A phase 3 obesity trial has now been published and the phase 3 program continues; no approved product exists.

Keep in mind

Phase 3 results do not establish long-term safety beyond the studied period or verify research-vial composition.

Identity and research status reviewRead the original sources

The research. What’s been studied.

TapClick a dotted word to see what it means.

  • Human evidence

    Weight reduction

    In the TRIUMPH-1 trial (2,339 adults with obesity), body weight fell 17.6% to 25.0% across doses, versus 3.9% on placebo. Retatrutide remains investigational.

  • Early human studies

    Liver fat

    A Phase 2 substudy found reduced liver fat in some participants. This does not establish a liver-disease treatment benefit.

  • Human evidence

    Blood sugar

    In the Phase 3 TRANSCEND-T2D-1 trial (537 adults with type 2 diabetes), A1c fell 1.69 to 1.94 points, versus 0.81 on placebo, over 40 weeks. This is not an approved use.

What do these labels mean?
  • Human evidence: approved-drug data or larger human studies, within the populations and uses studied.
  • Early human studies: small, preliminary or limited human studies.
  • Animal & lab studies: animal or laboratory findings that do not establish effects in people.
  • Unverified: a proposed use or claim without verified supporting clinical evidence.
How each claim was reviewed (4)

Reported effects and evidence.

A citation may support, qualify or correct a claim. Read the study scope; a laboratory result is not an established benefit in people. Each review covers a claim as it was first collected; the tiles above show the collection’s current wording.

  1. Human phase 2 RCT; time-sensitive ranking

    Review of “Largest weight loss in trials so far”

    The 2023 phase 2 trial reported 24.2% mean weight reduction at 48 weeks in the highest-dose group.

    Limitations and applicability. 24.2% at 48 weeks is trial-specific. “Largest so far” is unsupported without a dated comparison; phase-3 status needs current verification.

    Original collected claim and review history

    Original title: Largest weight loss in trials so far

    About 24% average weight loss at 48 weeks on the top dose in a Phase 2 trial; Phase 3 trials are underway.

    Original headline statistic: About 24%

    Original label: early. Preserved for traceability; the reviewed wording above qualifies this record.

    Record retatrutide:benefit:1 · Annotated 2026-10-01 · Review method

  2. Human phase 2 imaging substudy

    Review of “Clears liver fat”

    A phase 2 substudy found substantial MRI-measured liver-fat reductions; many higher-dose participants reached less than 5% liver fat.

    Limitations and applicability. MRI liver-fat normalization is not proof of curing MASH, fibrosis or clinical liver outcomes.

    Original collected claim and review history

    Original title: Clears liver fat

    In a Phase 2 sub-study, most people with fatty liver on the higher doses brought their liver fat back to normal levels.

    Original label: early. Preserved for traceability; the reviewed wording above qualifies this record.

    Record retatrutide:benefit:2 · Annotated 2026-10-01 · Review method

  3. Unknown — no direct primary source verified. Mechanistic hypothesis; direct human claim unverified

    Review of “Burns more energy”

    Glucagon-receptor activity may contribute to metabolic effects; the extent of increased human energy expenditure requires direct evidence.

    Limitations and applicability. Receptor pharmacology alone does not establish a measured energy-expenditure increase in trial participants.

    Unknown: no direct primary source verified. This does not mean that no research exists.

    Original collected claim and review history

    Original title: Burns more energy

    Its glucagon component raises energy expenditure on top of reducing appetite.

    Original label: early. Preserved for traceability; the reviewed wording above qualifies this record.

    Record retatrutide:benefit:3 · Annotated 2026-10-01 · Review method

  4. Human phase 2 and phase 3 RCTs

    Review of “Blood sugar control”

    Retatrutide lowered HbA1c in phase 2 and subsequent phase 3 diabetes research; keep each trial, population and endpoint separately identified.

    Limitations and applicability. The phase 2 result is historical; a 2026 TRANSCEND-T2D-1 phase 3 report now exists. Existing Bellido/TRIUMPH-2 citation was not independently verified.

    Original collected claim and review history

    Original title: Blood sugar control

    Lowered A1c in people with type 2 diabetes in Phase 2.

    Original label: early. Preserved for traceability; the reviewed wording above qualifies this record.

    Record retatrutide:benefit:4 · Annotated 2026-10-01 · Review method

The research in detail

Evidence category

Human trials, not approved

A 2023 Phase 2 obesity trial reported about 24% mean weight loss at 48 weeks on the highest studied dose. Phase 3 trials in obesity (TRIUMPH-1) and type 2 diabetes (TRANSCEND-T2D-1) were published in 2026, and the broader program is evaluating other conditions. Retatrutide remains investigational.

Evidence is assessed claim by claim above. Regulatory approval, study design, findings and relevance are separate questions; there is no single evidence score.

Risks and unknowns. What to know first.

Collected cautions follow. These are not an exhaustive or independently validated safety assessment; claim references do not automatically support every caution.

  • GI side effects like other incretin drugs, plus dose-related increases in heart rate.
  • Some trial participants reported abnormal skin sensations.
  • Long-term safety is still being studied.

What people report

Show all 8 cautionsShow fewer cautions

Read this first: what “research use only” means

Published dosing records. What the trials used.

Historical label and trial records for the named product, route, population and indication. These records are not a personal schedule or a validated regimen for a catalog vial. Source attribution does not establish applicability.

Phase 3 (TRIUMPH-2)

Phase 3 trial (TRIUMPH-2) in adults with obesity or overweight and type 2 diabetes (The Lancet, 2026)

Long-termClinical trial

Source: Bellido et al., The Lancet, 2026 (TRIUMPH-2)

How
Injection under the skin
How often
Once a week
How long
80 weeks in the trial

Dose, step by step

  1. Weeks 1–4 2 mg
  2. Weeks 5–8 4 mg
  3. Weeks 9–12 6 mg
  4. Weeks 13–16 9 mg
  5. Week 17 on 12 mg

Limit. Highest dose tested: 12 mg once a week.

  • Other groups: 4 mg (2 mg for 4 weeks, then 4 mg) and 9 mg (2, 4 and 6 mg for 4 weeks each, then 9 mg), plus a placebo group.
  • People gave themselves the injections.
  • A permanent dose cut was allowed for stomach or bowel side effects, or poor eating, that did not improve with other steps.
  • The step-by-step ramp comes from the trial’s published design paper (Giblin et al., 2026).

Phase 2 trial

Phase 2 trial in adults with obesity, or overweight plus a weight-related condition (New England Journal of Medicine, 2023)

Long-termClinical trial

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

How
Injection under the skin
How often
Once a week
How long
48 weeks in the trial

Dose, step by step

  1. Weeks 1–4 2 mg
  2. Weeks 5–8 4 mg
  3. Weeks 9–12 8 mg
  4. Week 13 on 12 mg

Limit. Highest dose tested: 12 mg once a week.

  • Other groups: 1 mg with no ramp; 4 mg (started at 2 mg or at 4 mg); 8 mg (started at 2 mg or at 4 mg); and placebo.
  • Starting at 2 mg rather than 4 mg partly reduced stomach and bowel side effects.

These doses were tested in clinical trials under medical supervision. They aren’t approved for use, and a research vial is not the product that was tested.

Community protocols. Reported online. Not clinically validated.

Community reports Collection date: 30 Sep 2026

Most grey-market users start well below the trial’s 2 mg (often 0.5–1.5 mg a week), step up slowly only when appetite control fades, and settle around 2–6 mg a week; app data put the typical dose at about 4 mg a week after 24 weeks.

More about this

A minority copy the trial ladder (2, 4, 6 mg and up every 4 weeks, to 8–12 mg), and about a third split the weekly dose into two or more shots.

Not testedFrequently encountered in reviewed sources

Start low, go slow

Collected report · exact form and route are only as reported below. Source date and reporter identity are not separately verified. Collection checked 30 Sep 2026; presentation annotated 2026-10-01.

Frequency labels describe this collection, not a measured population. Contradictory records remain available.

Details and sourcesHide details
Dose
Start at 0.5–1.5 mg; many settle at 1–6 mg
How often
Once a week
Route
Injection under the skin
Timing
Same day each week
How long
Open-ended, often many months
Cycle
Some taper down the same way they went up once at goal weight
Ramp
Step up by about 0.25–1 mg only when appetite control fades (anywhere from weekly to monthly); some “micro-titrate” in small weekly steps. When moving up from 2 mg, most go to 2.5–3 mg rather than 4 mg.
Mixing
Research vials (10, 20 or 30 mg are common) + bacteriostatic water; for example 20 mg + 3 mL, so 10 units is about 0.67 mg
  • “Lowest effective dose” is the dominant forum philosophy, partly because many users are not obese.
  • Users often blame early side effects on starting at 2 mg and restart lower.
Sources (4)

Not testedCommon

Copying the trial ladder

Collected report · exact form and route are only as reported below. Source date and reporter identity are not separately verified. Collection checked 30 Sep 2026; presentation annotated 2026-10-01.

Frequency labels describe this collection, not a measured population. Contradictory records remain available.

Details and sourcesHide details
Dose
2 mg, then 4 mg, 6 mg, and on to 8–12 mg
How often
Once a week
Route
Injection under the skin
How long
Open-ended
Ramp
Up one step every 4 weeks; many pause at 4–6 mg while still losing weight
  • Newcomers are often surprised that most forum users do not follow the trial schedule.
  • Some who restart after a break climb back quickly (for example 2, 4, 6, then 8 mg in weekly steps).
Sources (3)
Show all 6 protocolsShow fewer protocols

Not testedCommon

Split dosing

Collected report · exact form and route are only as reported below. Source date and reporter identity are not separately verified. Collection checked 30 Sep 2026; presentation annotated 2026-10-01.

Frequency labels describe this collection, not a measured population. Contradictory records remain available.

Details and sourcesHide details
Dose
Same weekly total, divided (for example 5 mg as 2 × 2.5 mg, or 10 mg as 3 shots)
How often
Two or three shots a week, or every 4–5 days
Route
Injection under the skin
  • Done to smooth out side effects or late-week hunger.
Sources (4)

Not testedSometimes seen

Low-dose “maintenance” or microdose

Collected report · exact form and route are only as reported below. Source date and reporter identity are not separately verified. Collection checked 30 Sep 2026; presentation annotated 2026-10-01.

Frequency labels describe this collection, not a measured population. Contradictory records remain available.

Details and sourcesHide details
Dose
0.5–1 mg (some drift between 0.5 and 2 mg week to week)
How often
Once a week
Route
Injection under the skin
How long
Months
Ramp
0.5 mg, then 1 mg over about 4 weeks
  • Sometimes combined with a small dose of tirzepatide.
Sources (4)

Not testedSometimes seen

Added on top of tirzepatide

Collected report · exact form and route are only as reported below. Source date and reporter identity are not separately verified. Collection checked 30 Sep 2026; presentation annotated 2026-10-01.

Frequency labels describe this collection, not a measured population. Contradictory records remain available.

Details and sourcesHide details
Dose
Retatrutide 2 mg, stepped up to about 4–6 mg, alongside 12–15 mg tirzepatide (tirzepatide sometimes reduced)
How often
Once a week each
Route
Injection under the skin
How long
Weeks to months
Ramp
Retatrutide raised every week or two if tolerated
  • Used by people who stalled on the maximum tirzepatide dose; others switch fully to retatrutide instead.
Sources (2)

Not testedFringe

Supplier-suggested start

Collected report · exact form and route are only as reported below. Source date and reporter identity are not separately verified. Collection checked 30 Sep 2026; presentation annotated 2026-10-01.

Frequency labels describe this collection, not a measured population. Contradictory records remain available.

Details and sourcesHide details
Dose
1.5 mg for 2 weeks, then 2 mg
How often
Once a week
Route
Injection under the skin
  • Some sellers give dosing advice with the vials.
Sources (1)

Where the numbers come from

The starting point is Lilly’s trial ladder (2 mg to start, 4-week steps up to 12 mg), but Reddit has moved to lower starts (0.5–1 mg) and a “lowest effective dose” approach, partly because many users are not obese. App data confirm most users climb more slowly and stop lower than the trials.

Research notes

What is sold as retatrutide may not be retatrutide: clinicians quoted by Medscape doubt users are getting the real drug, and the Victorian alert suspects contamination. At least 50 US clinics were reported to be advertising retatrutide in 2026, but no clinic dosing protocol was found. Lilly plans to file for approval in the first quarter of 2027. Some users stack it with tirzepatide, cagrilintide or eloralintide, which confuses side-effect reports.

Taken with

Measurement basics and calculator

Explore vial arithmetic

What it is. In plain English.

An investigational triple-receptor drug with published Phase 3 obesity results.

An investigational peptide designed to activate , GLP-1 and glucagon receptors. Research-vial products are not approved pharmaceutical products.

It is designed to activate GLP-1, GIP and glucagon receptors. GLP-1 and GIP signaling can affect appetite and glucose regulation; the added glucagon-receptor activity is being studied for possible effects on energy use and liver fat. These proposed mechanisms do not establish clinical benefit.

Reviewed 2026-10-01.

Structure. What it really looks like.

Experimental

Cryo-EM structure of retatrutide (coral) bound to the human GLP-1 receptor (gray).

Retatrutide (coral) bound to the human GLP-1 receptor (gray), one of the three receptors it acts on. Also part of the experiment, but not drawn: a G protein and an antibody fragment.

Missing parts

  • The entry covers only the first 30 of retatrutide’s 39 amino acids, and it has no fatty-acid side chain.

8YW3, Li et al., 2024. Rendered with Mol* (Sehnal et al., 2021) from RCSB PDB data (Berman et al., 2000).

Specs. The facts at a glance.

Length
39 amino acids + fatty-acid chain
Sold as
  • NXP-3P kit · 6, 10, 12, 20, 24 or 48 mg
Regulatory status
Investigational. Not FDA-approved; no approved product identified. Results from Lilly-sponsored trials do not establish the identity or quality of research-vial products.
Also known as
Eli Lilly’s experimental “triple agonist”

Sources. What this page rests on.

Every source behind this page, with what it says and when it was checked, is in the Source library.

Retatrutide in the Source library

Original overview and research notes · annotated 2026-10-01

Historical collection text. Read alongside the claim corrections above; identity or evidence qualifications may supersede this wording.

Experimental next-generation weight loss

An experimental triple-hormone drug with the largest weight loss seen in trials so far.

A 39-amino-acid peptide engineered to activate three hormone receptors at once. Sold here under the code NXP-3P. It isn’t approved anywhere, so any vial sold online was made outside Eli Lilly’s supply chain.

It activates GLP-1 and GIP receptors like tirzepatide and adds the glucagon receptor. Glucagon signaling raises energy expenditure and helps clear fat from the liver, on top of the appetite effects.

A Phase 2 trial (NEJM, 2023) reported average weight loss of about 24% at 48 weeks on the top dose. Lilly’s Phase 3 TRIUMPH program is testing it for obesity, knee osteoarthritis, sleep apnea and other conditions.

Original status record: Investigational. Not approved by the FDA or any other regulator.

More in Weight & metabolism.

Glossary

GLP-1 / GIP

Gut hormones released after eating that raise insulin and reduce appetite. The basis of today’s weight-loss drugs.

Full glossary

Glossary

Phase 1 / 2 / 3

Stages of human drug testing: safety in a few people, then effectiveness in hundreds, then large confirmatory trials in thousands. Most compounds fail along the way.

Full glossary

Glossary

Cryo-EM

Cryo-electron microscopy. Molecules are frozen in a thin layer of ice and photographed thousands of times with an electron microscope; the images are combined into a 3D map.

Full glossary

Glossary

Resolution

How sharp a structure is, measured in ångströms (Å; a ten-billionth of a meter). Smaller is sharper.

Full glossary

Glossary

Protein Data Bank (PDB)

The free worldwide archive of 3D structures of proteins and other molecules measured in experiments. Each entry has a four-character code, like 7KI0.

Full glossary