Regulated as medicinal products

Retatrutide

Last reviewed

Reviewed by HelixEvoLabs Research Team

Technical and regulatory reference for retatrutide, an investigational peptide holding no marketing authorisation in any jurisdiction.

Identity and nomenclature

INN
retatrutide
Synonyms
retatrutidum
Development codes
LY3437943, LY-3437943

Mechanism

Retatrutide is a synthetic 39-residue acylated peptide characterised by the World Health Organization as an agonist at the glucagon, gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors.

The triple-agonist pharmacological class is stated in the World Health Organization proposed international nonproprietary name entry, which is the definitive public record of the molecule’s identity and substitution pattern.

No approved product labelling exists for this compound in any jurisdiction, so no regulator has published a mechanism-of-action characterisation of the kind found in an approved summary of product characteristics.

Analytical and manufacturing profile

Analytical data sheet

Retatrutide

Identity

Molecular formula
C221H342N46O68
Molecular weight
Not verified
CAS number
2381089-83-2
UNII
NOP2Y096GV
Chemical name
L-tyrosyl-2-methylalanyl-L-glutaminylglycyl-L-threonyl-L-phenylalanyl-L-threonyl-L-seryl-L-α-aspartyl-L-tyrosyl-L-seryl-L-isoleucyl-2-methyl-L-leucyl-L-leucyl-L-α-aspartyl-L-lysyl-N6-{2-[2-(2-{[N-(19-carboxynonadecanoyl)-L-γ-glutamyl]amino}ethoxy)ethoxy]acetyl}-L-lysyl-L-alanyl-L-glutaminyl-2-methylalanyl-L-alanyl-L-phenylalanyl-L-isoleucyl-L-α-glutamyl-L-tyrosyl-L-leucyl-L-leucyl-L-α-glutamylglycylglycyl-L-prolyl-L-seryl-L-serylglycyl-L-alanyl-L-prolyl-L-prolyl-L-prolyl-L-serinamide
Appearance
Not verified

Primary structure

YAQGTFTSDYSILLDKKAQAAFIEYLLEGGPSSGAPPPS

39 residues

Modifications

  • Positions 2 and 20 are 2-aminoisobutyric acid (Aib, 2-methyl-alanine). The one-letter sequence encodes both as A, so a plain copy of the one-letter string loses these substitutions.
  • Position 13 is 2-methyl-L-leucine, encoded as L in the one-letter sequence.
  • The C-terminus at position 39 is L-serinamide, that is, the peptide is C-terminally amidated rather than terminating in a free acid.
  • The Lys17 ε-amino group is acylated. Reading outward from the residue: one AEEA unit ([2-(2-aminoethoxy)ethoxy]acetyl), then a γ-glutamyl spacer, then a C20 α,ω-fatty diacid with a free terminal carboxyl (19-carboxynonadecanoyl).
  • The linker carries one AEEA unit. Semaglutide and tirzepatide each carry two, and the three are easily confused when comparing acylation architectures.
  • The FDA Global Substance Registration System record publishes a molecular formula and weight typed ESTIMATED that correspond to the unmodified 39-mer free acid and omit the Aib substitutions, the α-methyl-leucine, the C-terminal amide and the acyl conjugate. They should not be used as this compound’s formula.

Solubility

No solubility data established from a primary source.

Storage

No storage conditions established from a primary source.

Stability

No stability data established from a primary source.

Analytical methods

No validated method or acceptance criterion is published for this compound in a primary source. Where an approved product exists, limits are commonly withheld from the public assessment record as commercially confidential.

Impurities and degradation products

No impurity profile established from a primary source.

Handling

  • The Therapeutic Goods Administration states that describing a product as being for research use only does not change its regulatory status, permit importation, or remove supply and advertising obligations.
  • The FDA has issued warning letters to companies selling unapproved products containing retatrutide that were labelled for research purposes or not for human consumption, treating website claims as evidence of intended human drug use.
  • The developer states that retatrutide is an investigational molecule that cannot be legally sold or marketed for human use.

Clinical development

Phase 2 obesity trial

NCT04881760
Phase
2
Enrolment
338
Duration
48 weeks
Status
reported
Population
Adults aged 18 to 75 with obesity, or overweight with a weight-related comorbidity, and without type 1 or type 2 diabetes
Primary endpoint
Mean percentage change from baseline in body weight at week 24. The week 48 figures more commonly quoted are a secondary timepoint

Reported outcomes

Outcomes as reported by Phase 2 obesity trial, attributed to trial arm and timepoint
MetricArmValueComparatorTimepoint
Mean percentage change from baseline in body weight (registered primary endpoint)Retatrutide 1 mg-7.18% (SE 0.67)Placebo -1.55% (SE 0.54)Week 24
Mean percentage change from baseline in body weight (registered primary endpoint)Retatrutide 8 mg, escalated from 4 mg-18.26% (SE 0.95)Placebo -1.55% (SE 0.54)Week 24
Mean percentage change from baseline in body weight (registered primary endpoint)Retatrutide 12 mg, escalated from 2 mg-17.39% (SE 0.69)Placebo -1.55% (SE 0.54)Week 24
Mean percentage change from baseline in body weight (secondary timepoint)Retatrutide 1 mg-8.67% (SE 0.95)Placebo -2.11% (SE 0.73)Week 48
Mean percentage change from baseline in body weight (secondary timepoint)Retatrutide 4 mg, escalated from 2 mg-16.32% (SE 1.58)Placebo -2.11% (SE 0.73)Week 48
Mean percentage change from baseline in body weight (secondary timepoint)Retatrutide 8 mg, escalated from 4 mg-23.88% (SE 1.51)Placebo -2.11% (SE 0.73)Week 48
Mean percentage change from baseline in body weight (secondary timepoint)Retatrutide 12 mg, escalated from 2 mg-24.22% (SE 1.24)Placebo -2.11% (SE 0.73)Week 48
Most common adverse events, all retatrutide arms pooled, reported qualitatively without per-arm incidenceAll retatrutide arms pooledGastrointestinal events, described as dose-related and mostly mild to moderate; heart rate increases described as dose-dependent and peaking at week 24—Over 48 weeks

Figures as reported by this trial. They are not statements about what the compound does for a person.

Who this trial excluded

The trial establishes nothing about these groups. An outcome table cannot show this, so it is recorded alongside the results.

  • Type 1 or type 2 diabetes mellitus — this was a non-diabetic population
  • Age under 18 or over 75 years
  • Body mass index above 50, or between 27 and 30 without hypertension, dyslipidaemia or cardiovascular disease
  • Weight change greater than 5 kg in the previous 3 months
  • Prior or planned surgery for obesity
  • Use of medications that promote weight loss or cause weight gain
  • Myocardial infarction, stroke or hospitalisation for congestive heart failure in the previous 3 months
  • Uncontrolled high blood pressure
  • Renal impairment with estimated glomerular filtration rate below 45 mL/min/1.73 m2
  • Liver disease other than non-alcoholic fatty liver disease
  • History of acute or chronic pancreatitis, symptomatic gallbladder disease, or documented HIV infection
  • Active cancer within the previous 5 years
  • A major problem with depression or other mental illness within the previous 2 years
  • Family or personal history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma
  • Pregnancy, breastfeeding, intention to become pregnant, or childbearing potential without adequate contraception
  • Excessive alcohol intake, or marijuana use within the previous 3 months
Sponsor Eli Lilly and Company · New England Journal of Medicine, 2023 · doi:10.1056/NEJMoa2301972 · PMID 37366315 · verified 2026-07-31

TRIUMPH-1

NCT05929066

Topline results only — not peer reviewed

Phase
3
Enrolment
2335
Duration
80 weeks
Status
reported
Population
Adults with obesity or overweight without type 2 diabetes, including prespecified subsets with knee osteoarthritis and with obstructive sleep apnoea
Primary endpoint
Percentage change from baseline in body weight at week 80, with co-primary endpoints for the osteoarthritis pain subscale and the apnoea-hypopnoea index in their respective subsets, and a further co-primary for percentage weight change at week 104

Reported outcomes

Outcomes as reported by TRIUMPH-1, attributed to trial arm and timepoint
MetricArmValueComparatorTimepoint
Percentage change from baseline in body weightRetatrutide 4 mg-19.0% (-21.4 kg)Placebo -2.2% (-2.5 kg)Week 80
Percentage change from baseline in body weightRetatrutide 9 mg-25.9% (-29.2 kg)Placebo -2.2% (-2.5 kg)Week 80
Percentage change from baseline in body weightRetatrutide 12 mg-28.3% (-31.9 kg)Placebo -2.2% (-2.5 kg)Week 80
Change from baseline in waist circumferenceRetatrutide 12 mg-24.1 cmPlacebo -3.6 cmWeek 80
Proportion achieving body weight reduction of 30 per cent or moreRetatrutide 12 mg45.3%Placebo 0.5%Week 80
Percentage change from baseline in body weight, pre-specified extension in participants with body mass index of 35 or aboveRetatrutide 12 mg continued to maximum tolerated dose-30.3% (-38.5 kg)Placebo switched to maximum tolerated dose -19.2%Week 104

Figures as reported by this trial. They are not statements about what the compound does for a person.

Who this trial excluded

The trial establishes nothing about these groups. An outcome table cannot show this, so it is recorded alongside the results.

  • Diabetes mellitus — participants with type 2 diabetes were enrolled in TRIUMPH-2 instead
  • Age under 18. Note there was no upper age limit, unlike the phase 2 trial
  • Body mass index below 30, or below 27 with none of hypertension, dyslipidaemia, obstructive sleep apnoea or cardiovascular disease
  • Self-reported or documented weight change greater than 5 kg within 90 days
  • Weight loss drugs, including over-the-counter medicines, within 90 days before screening
  • Prior or planned surgical treatment for obesity
  • Family or personal history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2
  • Any history of pancreatitis
  • In the knee osteoarthritis substudy: steroid joint injections within 90 days, other joint injections or procedures within 6 months, or joint disease other than osteoarthritis
  • In the sleep apnoea substudy: stimulants, hypnotics, mirtazapine, opioids, trazodone or zonisamide within 3 months, or use of a dental appliance or other non-PAP device for sleep apnoea
  • The registered exclusion list for this trial is markedly shorter than the phase 2 trial and posts no cardiovascular, renal, hepatic, malignancy, psychiatric or pregnancy criteria. Their absence from the registry should not be read as their absence from the protocol
Sponsor Eli Lilly and Company · verified 2026-07-30

TRIUMPH-2

NCT05929079

Topline results only — not peer reviewed

Phase
3
Enrolment
1152
Duration
80 weeks
Status
reported
Population
Adults with type 2 diabetes and obesity or overweight, including a prespecified subset with obstructive sleep apnoea
Primary endpoint
Percentage change from baseline in body weight at week 80, with a co-primary endpoint for the apnoea-hypopnoea index in the sleep apnoea subset

Reported outcomes

Outcomes as reported by TRIUMPH-2, attributed to trial arm and timepoint
MetricArmValueComparatorTimepoint
Percentage change from baseline in body weightRetatrutide 4 mg-12.7% (-13.5 kg)Placebo -4.0% (-4.2 kg)Week 80
Percentage change from baseline in body weightRetatrutide 9 mg-19.1% (-20.6 kg)Placebo -4.0% (-4.2 kg)Week 80
Percentage change from baseline in body weightRetatrutide 12 mg-20.8% (-22.5 kg)Placebo -4.0% (-4.2 kg)Week 80
Change from baseline in glycated haemoglobin, from a baseline of 7.7 per centRetatrutide 9 mg-1.6 percentage pointsPlacebo -0.2 percentage pointsWeek 80

Figures as reported by this trial. They are not statements about what the compound does for a person.

Sponsor Eli Lilly and Company · verified 2026-07-30

TRIUMPH-3

NCT05882045

Topline results only — not peer reviewed

Phase
3
Enrolment
1946
Duration
80 weeks
Status
reported
Population
Adults with severe obesity and established cardiovascular disease, defined as prior myocardial infarction, prior stroke, or symptomatic peripheral arterial disease
Primary endpoint
Percentage change from baseline in body weight at week 80

Reported outcomes

Outcomes as reported by TRIUMPH-3, attributed to trial arm and timepoint
MetricArmValueComparatorTimepoint
Percentage change from baseline in body weightRetatrutide 9 mg-21.6% (-23.9 kg)Placebo -3.2% (-3.5 kg)Week 80
Percentage change from baseline in body weightRetatrutide 12 mg-22.6% (-25.3 kg)Placebo -3.2% (-3.5 kg)Week 80
Time to first major adverse cardiovascular event, five-component composite, pre-specified analysisRetatrutide 9 mg and 12 mg pooledHazard ratio 0.82, 95% CI 0.55 to 1.22; 44 eventsPlacebo 52 eventsOver the study treatment period
Time to first major adverse cardiovascular event, three-component composite, pre-specified analysisRetatrutide 9 mg and 12 mg pooledHazard ratio 1.12, 95% CI 0.64 to 1.96; 27 eventsPlacebo 23 eventsOver the study treatment period

Figures as reported by this trial. They are not statements about what the compound does for a person.

Sponsor Eli Lilly and Company · verified 2026-07-30

TRIUMPH-4

NCT05931367

Topline results only — not peer reviewed

Phase
3
Enrolment
445
Duration
68 weeks
Status
reported
Population
Adults with obesity or overweight and osteoarthritis of the knee meeting American College of Rheumatology criteria
Primary endpoint
Change from baseline in the osteoarthritis pain subscale score and percentage change from baseline in body weight, both at week 68

Reported outcomes

Outcomes as reported by TRIUMPH-4, attributed to trial arm and timepoint
MetricArmValueComparatorTimepoint
Percentage change from baseline in body weightRetatrutide 9 mg-26.4% (-29.1 kg)Placebo -2.1% (-2.1 kg)Week 68
Percentage change from baseline in body weightRetatrutide 12 mg-28.7% (-32.3 kg)Placebo -2.1% (-2.1 kg)Week 68
Change from baseline in the WOMAC pain subscale score, from a baseline of 6.0; the pre-specified measure is the absolute point changeRetatrutide 9 mg-4.5 pointsPlacebo -2.4 pointsWeek 68
Change from baseline in the WOMAC pain subscale score, from a baseline of 6.0Retatrutide 12 mg-4.4 pointsPlacebo -2.4 pointsWeek 68
Proportion achieving body weight reduction of 30 per cent or moreRetatrutide 12 mg39.4%Placebo 0.8%Week 68

Figures as reported by this trial. They are not statements about what the compound does for a person.

Sponsor Eli Lilly and Company · verified 2026-07-30

TRANSCEND-T2D-1

NCT06354660
Phase
3
Enrolment
537
Duration
40 weeks
Status
reported
Population
Adults aged 18 years and over with type 2 diabetes inadequately controlled by diet and exercise, with glycated haemoglobin between 7.0 and 9.5 per cent and a body mass index of at least 23
Primary endpoint
Change in glycated haemoglobin from baseline to week 40

Reported outcomes

Outcomes as reported by TRANSCEND-T2D-1, attributed to trial arm and timepoint
MetricArmValueComparatorTimepoint
Change from baseline in glycated haemoglobinRetatrutide 4 mg-1.69 percentage points; difference versus placebo -0.88, p<0.0001Placebo -0.81 percentage pointsWeek 40
Change from baseline in glycated haemoglobinRetatrutide 9 mg-1.86 percentage points; difference versus placebo -1.04, p<0.0001Placebo -0.81 percentage pointsWeek 40
Change from baseline in glycated haemoglobinRetatrutide 12 mg-1.94 percentage points; difference versus placebo -1.12, p<0.0001Placebo -0.81 percentage pointsWeek 40
Percentage change in body weight (secondary endpoint)Retatrutide 4 mg-11.5%Placebo -2.6%Week 40
Percentage change in body weight (secondary endpoint)Retatrutide 9 mg-13.9%Placebo -2.6%Week 40
Percentage change in body weight (secondary endpoint)Retatrutide 12 mg-15.3%Placebo -2.6%Week 40

Figures as reported by this trial. They are not statements about what the compound does for a person.

Sponsor Eli Lilly and Company · The Lancet, 2026 · doi:10.1016/S0140-6736(26)00967-0 · PMID 42250575 · verified 2026-08-05

Regulatory status by jurisdiction

  • United States

    FDA
    Investigational — no marketing authorisation

    No marketing authorisation and no approved application. The FDA has stated in enforcement correspondence that products containing retatrutide are unapproved new drugs, and the developer stated on 23 July 2026 that it is still completing the Chemistry, Manufacturing and Controls package required for a Biologics License Application it plans to submit in the first quarter of 2027.

    FDA Warning Letter, MARCS-CMS 695663Verified 2026-07-30

  • European Union

    European Medicines Agency
    Investigational — no marketing authorisation

    No marketing authorisation. Retatrutide is absent from the European Medicines Agency medicines register and from the list of medicines under evaluation, and the developer states that global submissions remain pending.

    Lilly’s triple agonist retatrutide: successful results from two additional studiesVerified 2026-07-30

  • United Kingdom

    MHRA
    Investigational — no marketing authorisation

    No marketing authorisation. The MHRA products database returns no result for retatrutide.

    MHRA products database search result for retatrutideVerified 2026-07-30

  • Australia

    TGA
    Investigational — no marketing authorisation

    Not included in the Australian Register of Therapeutic Goods. The Therapeutic Goods Administration names retatrutide among unapproved peptide products and states that such goods have not been included in the Register.

    Understanding your responsibilities when importing, compounding and supplying unapproved peptide productsVerified 2026-07-30

  • Canada

    Health Canada
    Investigational — no marketing authorisation

    Not authorised. Health Canada lists retatrutide among examples of unauthorised injectable peptide drugs it has seized, and states that unauthorised drug products are illegal in Canada and have not been assessed for safety, efficacy or quality.

    Think twice about injecting peptides bought online — unauthorized products can seriously harmVerified 2026-07-30

  • Switzerland

    Swissmedic
    Investigational — no marketing authorisation

    Not authorised. Swissmedic has stated that the substance is still in clinical development and is not authorised internationally, while noting that it is already available on the black market.

    Swissmedic warning regarding GLP-1 productsVerified 2026-07-30

Supply classification and permitted use

Retatrutide is an investigational compound. It holds no marketing authorisation in any jurisdiction, and human administration outside an authorised clinical trial is not a lawful supply route. HelixEVO does not supply this material for human administration.

  • Multiple regulators have published enforcement positions specific to this compound, including the FDA, the Therapeutic Goods Administration, Health Canada and Swissmedic.
  • Regulators have stated that labelling material as being for research use only does not alter its regulatory status or make its supply lawful.
  • No Chemistry, Manufacturing and Controls package has been published for this compound, and no pharmacopoeial monograph exists.

How supply classifications work · Documented safety signals

References

  1. [1]NomenclatureWHO Drug Information Vol. 36, No. 4, 2022 — Proposed INN: List 128 — World Health Organization, 2022 · accessed
  2. [2]RegulatorRETATRUTIDE — Global Substance Registration System record, UNII NOP2Y096GV — US Food and Drug Administration, 2026 · accessed
  3. [3]RegulatorFDA Warning Letter, MARCS-CMS 695663 — US Food and Drug Administration, 2024 · accessed
  4. [4]RegulatorFDA’s concerns with unapproved GLP-1 drugs used for weight loss — US Food and Drug Administration, 2026 · accessed
  5. [5]RegulatorMHRA products database search result for retatrutide — Medicines and Healthcare products Regulatory Agency, 2026 · accessed
  6. [6]RegulatorUnderstanding your responsibilities when importing, compounding and supplying unapproved peptide products — Therapeutic Goods Administration, 2026 · accessed
  7. [7]RegulatorThink twice about injecting peptides bought online — unauthorized products can seriously harm — Health Canada, 2026 · accessed
  8. [8]RegulatorSwissmedic warning regarding GLP-1 products — Swissmedic, 2025 · accessed
  9. [9]DeveloperLilly’s triple agonist retatrutide: successful results from two additional studies — Eli Lilly and Company, 2026 · accessed