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Research Catalog

Compound monograph

Retatrutide

Retatrutide, development code LY3437943, is a single peptide characterized as an agonist at GCGR, GIPR, and GLP-1R in its discovery record.

Published: 2026-09-04Last updated: 2026-10-13Literature/identifier verification: 2026-08-23
Also known asLY3437943
Multi-receptor incretin analogs

01

Identity & nomenclature

Retatrutide, development code LY3437943, is a single peptide characterized as an agonist at GCGR, GIPR, and GLP-1R in its discovery record.

Retatrutide is the adopted name used for the development compound LY3437943 in the verified bibliography. It is a proposed International Nonproprietary Name, published in WHO Proposed INN List 128 (WHO Drug Information, Vol. 36, No. 4, 2022). PubChem CID 171934787 encodes a fully stereospecified free-peptide candidate despite its sodium-salt title; its position-13 configuration matches the GSRS systematic definition, but this record’s independent configuration conflict remains unresolved.

Declared aliases and development codes: LY3437943.

02

Molecular properties

CAS Registry Number2381089-83-2
UNIINOP2Y096GV
Terminal groupsFree N-terminus; C-terminal amidation

Described in words and attributed, not recorded as a verified structure. WHO Proposed INN List 128 describes retatrutide as a 39-residue peptide with a C-terminal amide. In three-letter symbols, the residue order it gives is Tyr-Aib-Gln-Gly-Thr-Phe-Thr-Ser-Asp-Tyr-Ser-Ile-αMeLeu-Leu-Asp-Lys-Lys-Ala-Gln-Aib-Ala-Phe-Ile-Glu-Tyr-Leu-Leu-Glu-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser, where Aib is 2-aminoisobutyric acid (positions 2 and 20) and αMeLeu is 2-methylleucine (position 13), which the WHO entry specifies as the L form. The lysine at position 17 carries a side chain on its ε-amino group, built outward from one 8-amino-3,6-dioxaoctanoyl unit, one γ-glutamyl unit and eicosanedioic acid attached as a mono-amide. No one-letter string is recorded, because a letter string cannot show the three non-standard residues or the side chain. The same residue order and side-chain construction appear in the sponsor patent WO2019125938A1 and in an independently authored synthesis patent, CN117024528B. The drawing of the position-13 residue in CN117024528B shows the opposite configuration to the one WHO specifies; whether that is a different stereoisomer or a drawing error is not established here.

03

Structural characteristics

Like tirzepatide, retatrutide is built on a GIP scaffold rather than a GLP-1 scaffold, with a different substitution set, lipidation position and spacer. The related GIP(1-42) entry identifies scaffold ancestry; GLP-1(7-36) amide and glucagon are native receptor comparators. Activity at the GLP-1 and glucagon receptors is engineered pharmacology and does not make retatrutide a GLP-1-derived or glucagon-derived peptide. Tirzepatide's modification table does not apply to it. The residue order and the lysine side chain are given in the sequence notes as WHO Proposed INN List 128 describes them; they are attributed statements, and one point of configuration is disputed between sources. The CAS registry number and UNII are recorded from the FDA/NCATS GSRS substance record, which lists both on the retatrutide entry. No PubChem CID is published here: PubChem links several compound records to substance records carrying this name, those records differ from one another in stereochemical detail and in one case in composition, and none has been matched to an independently established structure.

Terminal features: Free N-terminus, C-terminal amidation.

04

Molecular targets & mechanisms

Glucagon-like peptide-1 receptor

GLP-1R

GLP-1R is a class B G-protein-coupled receptor. The cited structural and pharmacology records characterize semaglutide and retatrutide as peptide agonists at this receptor.

Glucose-dependent insulinotropic polypeptide receptor

GIPR

GIPR is a class B G-protein-coupled receptor. The cited discovery and trial records identify it as one of the three receptor relationships declared for retatrutide.

Glucagon receptor

GCGR

GCGR is a class B G-protein-coupled receptor. Retatrutide's LY3437943 discovery record characterizes a molecular agonist relationship at GCGR alongside GIPR and GLP-1R.

05

Analytical considerations

No molecular formula or molecular mass is recorded as a field, because two public records print different values. WHO Proposed INN List 128 prints C221H342N46O68 for the free peptide; counting the atoms of the structure it describes gives the same formula and an average mass of about 4731.4 Da. The FDA/NCATS GSRS substance record lists an estimated formula of C187H281N43O60 and a calculated mass of 4091.5 Da, which are the values for the 39-residue chain written with standard amino acids and free termini, without the non-standard residues, the C-terminal amide or the lysine side chain. Analytical identity values are not inferred from catalog copy or from structurally related peptides.

Disagreements and mix-ups

Points where sources disagree about this compound's identity, or where a name or form is easily confused with another, as noted in this record. The discrepancy register quotes the passage for each one.

What the studies reported

Each finding describes one cited study in its stated model. These observations are specific to that study and do not establish effects in other settings.

Cell and tissue studies

  • GCGR, GIPR and GLP-1R activity assays

    Coskun et al. reported balanced GCGR and GLP-1R activity and greater GIPR activity for LY3437943 in in-vitro receptor assays.

    Reference [1]

Animal studies

  • Obese mice

    Coskun et al. observed decreased body weight and improved glycemic control in obese mice exposed to LY3437943.

    Reference [1]

06

Verified bibliography

Cited studies by type

The 9 papers this record cites, counted by the kind of work each reports. A count is the size of this record's selection, not of the research that exists, and says nothing about results, safety, effectiveness or approval.

A paper can report more than one kind of work. Each count opens those papers in the bibliography. Compare every record on the Evidence Map.

  1. Reference 1

    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, Qu H, Loghin C, Moyers JS, O'Farrell LS, Briere DA, Sloop KW, Thomas MK, Pirro V, Wainscott DB, Willard FS, Abernathy M, Morford L, Du Y, Benson C, Gimeno RE, Haupt A, Milicevic Z

    Cell metabolism · 2022-08-18 · Journal Article

    current
    PMID 35985340DOI 10.1016/j.cmet.2022.07.013RetatrutideGLP-1RGIPRGCGR

  2. Reference 2

    Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial.

    Jastreboff AM, Kaplan LM, Frías JP, Wu Q, Du Y, Gurbuz S, Coskun T, Haupt A, Milicevic Z, Hartman ML, Retatrutide Phase 2 Obesity Trial Investigators

    The New England journal of medicine · 2023-06-26 · Clinical Trial, Phase II

    current
    PMID 37366315DOI 10.1056/NEJMoa2301972RetatrutideGLP-1RGIPRGCGR

  3. Reference 3

    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, Du Y, Lou J, Gurbuz S, Thomas MK, Hartman ML, Haupt A, Milicevic Z, Coskun T

    Lancet (London, England) · 2023-06-26 · Clinical Trial, Phase II

    current
    PMID 37385280DOI 10.1016/S0140-6736(23)01053-XRetatrutideGLP-1RGIPRGCGR

  4. Reference 4

    Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial.

    Sanyal AJ, Kaplan LM, Frias JP, Brouwers B, Wu Q, Thomas MK, Harris C, Schloot NC, Du Y, Mather KJ, Haupt A, Hartman ML

    Nature medicine · 2024-06-10 · Clinical Trial, Phase II

    current
    PMID 38858523PMC11271400DOI 10.1038/s41591-024-03018-2RetatrutideGLP-1RGIPRGCGR

  5. Reference 5

    Pharmacology, physiology, and mechanisms of incretin hormone action.

    Campbell JE, Drucker DJ

    Cell metabolism · 2013-05-16 · Review

    current
    PMID 23684623DOI 10.1016/j.cmet.2013.04.008TirzepatideSemaglutideRetatrutideExenatideLiraglutideGLP-1RGIPR

  6. Reference 6

    Cryo-EM structure of the activated GLP-1 receptor in complex with a G protein.

    Zhang Y, Sun B, Feng D, Hu H, Chu M, Qu Q, Tarrasch JT, Li S, Sun Kobilka T, Kobilka BK, Skiniotis G

    Nature · 2017-05-24 · Journal Article

    current
    PMID 28538729PMC5587415DOI 10.1038/nature22394SemaglutideLiraglutideExenatideTirzepatideRetatrutideGLP-1R

  7. Reference 7

    Structural basis for ligand recognition of incretin receptors.

    Underwood CR, Parthier C, Reedtz-Runge S

    Vitamins and hormones · 2010 · Review

    current
    PMID 21094903DOI 10.1016/B978-0-12-381517-0.00009-6SemaglutideLiraglutideExenatideTirzepatideRetatrutideGLP-1RGIPR

  8. Reference 8

    Structure of the full-length glucagon class B G-protein-coupled receptor.

    Zhang H, Qiao A, Yang D, Yang L, Dai A, de Graaf C, Reedtz-Runge S, Dharmarajan V, Zhang H, Han GW, Grant TD, Sierra RG, Weierstall U, Nelson G, Liu W, Wu Y, Ma L, Cai X, Lin G, Wu X, Geng Z, Dong Y, Song G, Griffin PR, Lau J, Cherezov V, Yang H, Hanson MA, Stevens RC, Zhao Q, Jiang H, Wang MW, Wu B

    Nature · 2017-05-17 · Journal Article

    current
    PMID 28514451PMC5492955DOI 10.1038/nature22363RetatrutideGCGR

  9. Reference 9

    Structure of the glucagon receptor in complex with a glucagon analogue.

    Zhang H, Qiao A, Yang L, Van Eps N, Frederiksen KS, Yang D, Dai A, Cai X, Zhang H, Yi C, Cao C, He L, Yang H, Lau J, Ernst OP, Hanson MA, Stevens RC, Wang MW, Reedtz-Runge S, Jiang H, Zhao Q, Wu B

    Nature · 2018-01-03 · Journal Article

    current
    PMID 29300013DOI 10.1038/nature25153RetatrutideGCGR

Study models of these references

What kind of experiment each cited paper reports, taken from its abstract unless marked. Not a summary of results.

ReferenceStudy models
Coskun T et al. 2022Study models reported: in vitro; animal (mouse); human participants (interventional) · from the abstract
Jastreboff AM et al. 2023Study models reported: human participants (interventional) · from the abstract
Rosenstock J et al. 2023Study models reported: human participants (interventional) · from the abstract
Sanyal AJ et al. 2024Study models reported: human participants (interventional) · from the abstract
Campbell JE et al. 2013Review article
Zhang Y et al. 2017Study models reported: in vitro · from the abstract
Underwood CR et al. 2010Review article
Zhang H et al. 2017Study models reported: in vitro · from the abstract
Zhang H et al. 2018Study models reported: in vitro · from the abstract

Compare

Record history

Published 2026-09-04.

  • : Identity and nomenclature
  • : Identity and nomenclature, Sequence and structure, Analytical notes
  • : Sequence and structure
  • : Identity and nomenclature, Sequence and structure
  • : References

Each entry names the parts of this record that changed on that date. Changes to links between records and to catalogue links are not listed. This history covers the tracked record fields; study findings are not listed here.

Cite this record: Purely Peptides Research Library. Retatrutide. Published 2026-09-04; updated 2026-10-13. https://purelypeptides.org/research/compounds/retatrutide/

10

Methodology & citation verification

Reference identity is checked against official PubMed metadata. Local deterministic receipts bind each normalized title and canonical metadata record to its verification date. Scientific values remain absent when an authoritative source has not been verified.

Read the full methodology →