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Peptency Academy · Compound

Tirzepatide (LY3298176)

Tirzepatide (development code LY3298176) is a synthetic peptide of 39 amino acids built on the sequence of the hormone GIP and joined through a linker to a C20 fatty diacid. Source sentenceResults (PMC6308032): "LY3298176 is a 39 amino acid linear peptide conjugated to a C20 fatty diacid moiety via a linker connected to the lysine residue at position 20. The peptide sequence of LY3298176 also contains two non-coded amino acid residues at positions 2 and 13 (Aib, α-amino isobutyric acid), and the C-terminus is amidated (Figure 1A)."; Results heading (PMC6308032): "Discovery and Characterization of LY3298176, a GIP-based Dual Incretin Receptor Agonist"1 Mol Metab 2018 Receptor pharmacology papers describe it as a dual agonist at the GIP and GLP-1 receptors. Source sentenceTirzepatide (LY3298176) is a dual GIP and GLP-1 receptor agonist ...2 JCI Insight 20201 Mol Metab 2018 PubChem records it under CID 166567236 with the formula C225H348N48O68 and lists CAS 2023788-19-2 among its synonyms. Source sentenceCID 166567236: MolecularFormula C225H348N48O68; MolecularWeight 4813; synonyms "Tirzepatide", "2023788-19-2"3 PubChem CID 166567236

Version 1Edited Evidence through 36 sources

Regulatory content shown for: EU and UK.

Lipidated peptide

  • INN, code LY3298176Tirzepatide39 residuesabout 4813 DaSource sentenceResults (PMC6308032): "LY3298176 is a 39 amino acid linear peptide conjugated to a C20 fatty diacid moiety via a linker connected to the lysine residue at position 20. The peptide sequence of LY3298176 also contains two non-coded amino acid residues at positions 2 and 13 (Aib, α-amino isobutyric acid), and the C-terminus is amidated (Figure 1A)."1 Mol Metab 2018

Known, not known, contested

Known

  • Tirzepatide is a linear 39 residue peptide with two Aib residues (2-aminoisobutyric acid, positions 2 and 13), a C20 fatty diacid joined by a linker to the lysine at position 20, and an amidated C-terminus. Source sentenceResults (PMC6308032): "LY3298176 is a 39 amino acid linear peptide conjugated to a C20 fatty diacid moiety via a linker connected to the lysine residue at position 20. The peptide sequence of LY3298176 also contains two non-coded amino acid residues at positions 2 and 13 (Aib, α-amino isobutyric acid), and the C-terminus is amidated (Figure 1A)."1 Mol Metab 2018
  • Cryo-electron microscopy structures of tirzepatide bound to the GIP receptor and to the GLP-1 receptor were published in 2022. Source sentencewe determine cryo-electron microscopy structures of tirzepatide-bound GIPR and GLP-1R as well as peptide 20-bound GIPR, GLP-1R and GCGR4 Nat Commun 2022
  • Cell signalling studies measured cAMP generation, beta-arrestin recruitment and receptor internalisation for tirzepatide at the GIP and GLP-1 receptors. Source sentencesignaling studies demonstrate that tirzepatide mimics the actions of native GIP at the GIP receptor but shows bias at the GLP-1 receptor to favor cAMP generation over β-arrestin recruitment2 JCI Insight 2020
  • A radiolabel study measured circulating components, excretion and metabolic pathways of tirzepatide in humans, rats and monkeys. Source sentenceMetabolite analysis of tirzepatide revealed the parent drug was the major circulating component in human, rat, and monkey plasma. ... Intact tirzepatide was not observed in urine or feces in any species. Tirzepatide was primarily metabolized via proteolytic cleavage of the amino acid backbone, β-oxidation of the C20 diacid moiety, and amide hydrolysis.5 Eur J Pharm Sci 2024
  • PubMed held 2,612 records naming tirzepatide or LY3298176 on 14 Oct 2026; 136 carry the randomised controlled trial publication type and 946 the review type. Source sentenceesearch count 2612 for (tirzepatide[tiab] OR LY3298176[tiab]); with randomized controlled trial[pt] 136; with review[pt] 946; run 14 Oct 20266 PubMed search for tirzepatide and LY3298176, 14 October 20267 PubMed search for randomised trials of tirzepatide, 14 October 2026
  • ClinicalTrials.gov listed 298 studies with tirzepatide as an intervention on 14 Oct 2026; Eli Lilly and Company is the lead sponsor of 80 of them. Source sentencequery.intr tirzepatide: 298 studies; lead sponsor counts: Eli Lilly and Company 80, Brigham and Women's Hospital 11, Novo Nordisk A/S 6, The Cleveland Clinic 68 ClinicalTrials.gov search, 14 October 2026

Not known

Contested

  • PubChem draws tirzepatide in two ways under the same formula, C225H348N48O68. CID 166567236 (InChIKey BTSOGEDATSQOAF-MCNPHUAVSA-N) joins the C20 diacid to lysine 20 through the linker, as the 2018 discovery report describes. CID 156588324, the record PubChem titles Tirzepatide (InChIKey AAPYRSPHYSKGIS-MCNPHUAVSA-N), bonds the diacid directly to lysine 20 and places the linker after it. Checked 14 Oct 2026. Source sentenceCID 166567236 SMILES side chain on Lys20: CCCCNC(=O)COCCOCCNC(=O)COCCOCCNC(=O)CC[C@@H](C(=O)O)NC(=O)CCCCCCCCCCCCCCCCCCC(=O)O; CID 156588324 SMILES side chain on Lys20: CCCCNC(=O)CCCCCCCCCCCCCCCCCCC(=O)N[C@@H](CCC(=O)NCCOCCOCC(=O)NCCOCCOCC(=O)O)C(=O)O; CID 166567236 record description: "See also: Tirzepatide (annotation moved to)" linking CID 156588324; Coskun 2018 (PMC6308032): "conjugated to a C20 fatty diacid moiety via a linker connected to the lysine residue at position 20"22 PubChem name search for tirzepatide, 14 October 20263 PubChem CID 16656723623 PubChem CID 1565883241 Mol Metab 2018
  • Sources give different numbers for its mass: the 2018 discovery report gives 4810.52 Da, which matches the monoisotopic mass PubChem computes (4810.5249 Da), while PubChem's average mass is 4813. Source sentenceCoskun 2018, Results: "... of LY3298176 is 4810.52 Da."; PubChem CID 166567236: MolecularWeight 4813, MonoisotopicMass 4810.52485741 Mol Metab 20183 PubChem CID 166567236

Chemistry: tirzepatide as PubChem CID 166567236 records it

Sequence
YXEGTFTSDYSIXLDKIAQKAFVQWLIAGGPSSGAPPPS
Length
39 residues
Modifications
Aib (2-aminoisobutyric acid) at positions 2 and 13, C20 fatty diacid joined by a linker to Lys20, C-terminal amide
Formula
C225H348N48O68
Monoisotopic mass
4810.5249 Da
Average mass
4813 Da
CAS
2023788-19-2
PubChem CID
166567236
InChIKey
BTSOGEDATSQOAF-MCNPHUAVSA-N
Synonyms
LY3298176, tirzepatida, tirzepatidum
Salt form
No salt form stated in the record
Checked 14 October 2026 3 PubChem CID 166567236

Sequence

YXEGTFTSDYSIXLDKIAQKAFVQWLIAGGPSSGAPPPS

The 39 residues of tirzepatide in one letter code. X marks 2-aminoisobutyric acid (Aib) at positions 2 and 13. The lysine at position 20 carries the C20 fatty diacid through a linker, and the C-terminal serine is amidated.

Which molecule does a tirzepatide certificate describe?

  • Read the formula, mass and sequence on the certificate of analysis. Tirzepatide is C225H348N48O68 (monoisotopic mass 4810.5249 Da in PubChem), 39 residues with Aib at positions 2 and 13, a C20 fatty diacid on the lysine at position 20 and an amidated C-terminus. A different formula, mass or sequence describes a different molecule. Source sentencePubChem CID 166567236: C225H348N48O68, MonoisotopicMass 4810.5248574; Coskun 2018: "LY3298176 is a 39 amino acid linear peptide conjugated to a C20 fatty diacid moiety via a linker connected to the lysine residue at position 20. The peptide sequence of LY3298176 also contains two non-coded amino acid residues at positions 2 and 13 (Aib, α-amino isobutyric acid), and the C-terminus is amidated (Figure 1A)."3 PubChem CID 1665672361 Mol Metab 2018
  • A 2026 LC-HRMS method identifies tirzepatide by accurate mass and fragment ions and separates it from eight other GLP-1 receptor agonist peptides, among them semaglutide and retatrutide. Source sentenceA rapid, sensitive, and selective multiplexed liquid chromatography-high-resolution mass spectrometry (LC-HRMS) method was developed and validated for the identification and quantitation of nine structurally diverse peptide-based glucagon-like peptide-1 receptor agonists (GLP-1 RAs): bofanglutide, ecnoglutide, exenatide, liraglutide, mazdutide, retatrutide, semaglutide, survodutide, and tirzepatide ... combines high-resolution full-scan MS (HRMS) for accurate mass measurement with data-dependent HRMS/MS fragmentation for structural confirmation24 J Chromatogr A 2026

What is tirzepatide?

Tirzepatide, also called LY3298176, is a synthetic lipidated peptide of 39 amino acids whose sequence is based on the hormone GIP. Receptor pharmacology papers describe it as a dual agonist at the GIP and GLP-1 receptors. Regulator records for each market are in the status matrix below. Source sentenceCoskun 2018, Results: "LY3298176 is a 39 amino acid linear peptide conjugated to a C20 fatty diacid moiety"; Willard 2020: "Tirzepatide (LY3298176) is a dual GIP and GLP-1 receptor agonist"; PubChem CID 156588324 (DrugBank): "Its protein sequence was based on the sequence of endogenous GIP"1 Mol Metab 20182 JCI Insight 202023 PubChem CID 156588324

Is tirzepatide a peptide?

Yes. Tirzepatide is a linear chain of 39 amino acids, which makes it a peptide. Three features set it apart from a plain amino acid chain: 2-aminoisobutyric acid (Aib), an amino acid not coded by genes, at positions 2 and 13; a C20 fatty diacid joined by a linker to the lysine at position 20; and an amidated C-terminus. Source sentenceResults (PMC6308032): "LY3298176 is a 39 amino acid linear peptide conjugated to a C20 fatty diacid moiety via a linker connected to the lysine residue at position 20. The peptide sequence of LY3298176 also contains two non-coded amino acid residues at positions 2 and 13 (Aib, α-amino isobutyric acid), and the C-terminus is amidated (Figure 1A)."1 Mol Metab 2018

Is tirzepatide a GLP-1?

Not exactly. Tirzepatide is not the hormone GLP-1, and its sequence is based on a different hormone, GIP (glucose-dependent insulinotropic polypeptide). It binds and activates both the GIP receptor and the GLP-1 receptor, so pharmacology papers call it a dual GIP and GLP-1 receptor agonist. Source sentenceCoskun 2018, Results: "In receptor binding studies, LY3298176 binds either receptor with high affinity ... LY3298176 potently stimulates cAMP accumulation by either receptor"; PubChem CID 156588324 (DrugBank): "Its protein sequence was based on the sequence of endogenous GIP"; Willard 2020: "Tirzepatide (LY3298176) is a dual GIP and GLP-1 receptor agonist"1 Mol Metab 201823 PubChem CID 1565883242 JCI Insight 2020

How does tirzepatide work at its receptors?

At the receptor level, tirzepatide binds the GIP receptor with an affinity comparable to native GIP and the GLP-1 receptor about 5-fold more weakly than native GLP-1, and it stimulates cAMP signalling through both. At the GLP-1 receptor it favours cAMP over beta-arrestin recruitment, and receptor occupancy estimates show greater engagement of the GIP receptor. Source sentenceCoskun 2018, Results: "the affinity is comparable to native GIP for the GIPR and approximately 5-fold weaker than native GLP-1 for the GLP-1R ... LY3298176 potently stimulates cAMP accumulation by either receptor"; Willard 2020: "This analysis reveals a greater degree of engagement of tirzepatide for the GIP receptor than the GLP-1 receptor ... shows bias at the GLP-1 receptor to favor cAMP generation over β-arrestin recruitment"1 Mol Metab 20182 JCI Insight 2020

What is the molecular mass of tirzepatide?

For C225H348N48O68, PubChem gives a monoisotopic mass of 4810.5249 Da and an average mass of 4813. Computed from the formula with standard atomic masses, the average mass is 4813.53 Da. Mass spectrometry reads tirzepatide as multiply charged ions: a rat plasma method monitored m/z 1204.4. Source sentencePubChem CID 166567236: MolecularFormula C225H348N48O68, MolecularWeight 4813, MonoisotopicMass 4810.5248574; computed: 225 x 12.011 + 348 x 1.008 + 48 x 14.007 + 68 x 15.999 = 4813.527; PMID 41197390: "transitions of m/z 1204.4 → 1473.6 for tirzepatide"3 PubChem CID 16656723625 J Chromatogr B 2026

What has research studied about tirzepatide?

Published work covers the peptide's structure and receptor pharmacology in cell assays, mouse and rat studies, pharmacokinetic and radiolabel studies in people, and large randomised trials; PubMed held 2,612 records on 14 Oct 2026. This page maps a reviewed set of 10 studies by model and by what each measured. Source sentenceesearch count 2612 on 14 Oct 2026; reviewed set: PMIDs 30473097, 32730231, 35217653, 42603384, 41197390, 39243911, 33778934, 35674880, 42630988, 414064446 PubMed search for tirzepatide and LY3298176, 14 October 20262 JCI Insight 20204 Nat Commun 20225 Eur J Pharm Sci 202426 N Engl J Med 2025

Are there clinical trials of tirzepatide?

Yes. ClinicalTrials.gov listed 298 studies with tirzepatide as an intervention on 14 Oct 2026, 97 recruiting and 92 completed, with results posted for 47. The table below lists five completed records that link to papers on this page. Source sentencequery.intr tirzepatide: 298 studies; overallStatus RECRUITING 97, COMPLETED 92, NOT_YET_RECRUITING 62, ACTIVE_NOT_RECRUITING 33; hasResults true 478 ClinicalTrials.gov search, 14 October 2026

Is tirzepatide authorised in the EU?

EU

An approved medicine with this INN exists in the EU. The catalog item is not that medicine. Source sentenceEMA medicines data: active_substance tirzepatide, category Human, medicine_status Authorised (checked 14 Oct 2026)27 EMA medicines data, 14 October 2026

Is tirzepatide authorised in the UK?

UK

An approved medicine with this INN exists in the UK. The catalog item is not that medicine. Source sentenceGOV.UK press release, 8 Nov 2023: "The Medicines and Healthcare products Regulatory Agency (MHRA) has today (8 November 2023) authorised via a national application route, a new indication for the ... medicine, [name] (tirzepatide)"28 GOV.UK search for tirzepatide (MHRA items), 14 October 2026

Evidence map: tirzepatide

Primary studies of Tirzepatide (LY3298176), by model and by what was measured. Reviews are not counted. An empty cell means: not mapped yet.
ModelChemistry and analyticalPharmacokineticsReceptor binding and signallingTissue histologyBiomarkersClinical endpoint
Analytical only (no biological model)Chemistry and analytical2Not mapped yetNot mapped yetNot mapped yetNot mapped yetNot mapped yet
In vitro or ex vivoNot mapped yetNot mapped yetReceptor binding and signalling3Not mapped yetBiomarkers1Not mapped yet
RodentNot mapped yetPharmacokinetics2Not mapped yetTissue histology1Biomarkers1Not mapped yet
Other animalNot mapped yetPharmacokinetics1Not mapped yetNot mapped yetNot mapped yetNot mapped yet
Human, uncontrolledNot mapped yetPharmacokinetics3Not mapped yetNot mapped yetNot mapped yetNot mapped yet
Human, randomisedNot mapped yetPharmacokinetics1Not mapped yetNot mapped yetNot mapped yetClinical endpoint1

10 studies countedEvidence level facet: L4. A design scale, not a measure of strength or quality.

Counts only the 10 exact match studies reviewed for this page on 14 October 2026, out of 2,612 PubMed records for tirzepatide or LY3298176 (136 with the randomised controlled trial publication type). Studies that used several models are counted once in each model and measurement they report. Empty cells are not mapped yet. Reviews are never counted.

Who produced this evidence

  • The 2018 discovery report, the radiolabel study and both organ function pharmacokinetic studies state that their authors are employees and shareholders of Eli Lilly and Company; the 2020 receptor pharmacology paper lists Lilly Research Laboratories and NIH (NIDDK) grants. Source sentence30473097 competing interests (PMC6308032): "... are employees and shareholders of Eli Lilly and Company"; 39243911: "J.A.M., B.C., S.U., and K.C.C. are employees and shareholders of Eli Lilly and Company"; 33778934 and 35674880: "... are employees and shareholders of Eli Lilly and Company"; 32730231 affiliation "Quantitative Biology, Lilly Research Laboratories, Eli Lilly and Company", grants NIDDK NIH HHS1 Mol Metab 20185 Eur J Pharm Sci 202429 Clin Pharmacokinet 202130 Clin Pharmacokinet 20222 JCI Insight 2020
  • The SURPASS-CVOT paper states that the trial was funded by Eli Lilly. Source sentence(Funded by Eli Lilly; SURPASS-CVOT ClinicalTrials.gov number, NCT04255433.)26 N Engl J Med 2025
  • Four studies on this page come from groups without a Lilly affiliation: the cryo-EM structures (Fudan University), the LC-HRMS method (Government Laboratory, Hong Kong), the rat plasma method (Korea Research Institute of Bioscience and Biotechnology) and the mouse kidney study (South-Central Minzu University); each declares no competing interests. Source sentenceAffiliations: 35217653 School of Pharmacy, Fudan University; 42603384 Analytical and Advisory Services Division, Government Laboratory, Hong Kong; 41197390 Korea Preclinical Evaluation Center, Korea Research Institute of Bioscience and Biotechnology; 42630988 College of Life Sciences, South-Central Minzu University. COI: "The authors declare no competing interests" (35217653, 42630988); "The authors declare that they have no known competing financial interests" (42603384, 41197390)4 Nat Commun 202224 J Chromatogr A 202625 J Chromatogr B 202631 iScience 2026
  • On ClinicalTrials.gov, Eli Lilly and Company is the lead sponsor of 80 of the 298 studies that list tirzepatide as an intervention (14 Oct 2026); the next largest lead sponsor, Brigham and Women's Hospital, has 11. Source sentencequery.intr tirzepatide, 298 studies; lead sponsor counts: Eli Lilly and Company 80, Brigham and Women's Hospital 118 ClinicalTrials.gov search, 14 October 2026

Studies

  1. Human, randomisedMol Metab 2018

    Receptor binding and signalling in cell lines, studies in mice, and phase 1 safety, tolerability and pharmacokinetics in people

    Design
    Discovery report: receptor binding and signalling assays in cell lines, studies in mice, and a phase 1 randomised, placebo controlled, double-blind study with single and multiple ascending cohorts
    Population or model
    cell lines, mice, healthy participants and a patient cohort (NCT02759107)
    Molecule
    Tirzepatide (LY3298176) exact
    n
    142
    Comparator
    placebo; dulaglutide as positive control
    Blinding
    double-blind
    Funding
    Eli Lilly and Company (author affiliations and competing interests)

    Authors employed by Eli Lilly and Company (competing interests statement, PMC6308032).

    PubMed 30473097DOIcomment exchange: PubMed CommentIn

  2. In vitro or ex vivoJCI Insight 2020

    Receptor occupancy, cAMP and beta-arrestin signalling and receptor internalisation at the GIP and GLP-1 receptors

    Design
    Receptor occupancy modelling, cell signalling and receptor internalisation assays, and experiments in primary islets
    Population or model
    recombinant cell lines and primary islets
    Molecule
    Tirzepatide (LY3298176) exact
    Comparator
    native GIP and GLP-1
    Funding
    Eli Lilly and Company; NIH NIDDK grants

    Lilly Research Laboratories affiliation (PubMed).

    PubMed 32730231DOI

  3. In vitro or ex vivoNat Commun 2022

    Near-atomic structures of tirzepatide bound to the GIP receptor and to the GLP-1 receptor

    Design
    Cryo-electron microscopy structures of receptor complexes
    Population or model
    GIP receptor and GLP-1 receptor complexes
    Molecule
    Tirzepatide (LY3298176) exact
    Comparator
    peptide 20, a triple agonist

    The authors declare no competing interests (PubMed).

    PubMed 35217653DOI

  4. Analytical only (no biological model)J Chromatogr A 2026

    LC-HRMS identification and quantitation of nine GLP-1 receptor agonist peptides, tirzepatide among them

    Design
    Analytical method development and validation (LC-HRMS with HRMS/MS fragmentation), applied to marketed formulations
    Population or model
    none (chemistry and analytical)
    Molecule
    Tirzepatide (LY3298176) exact

    The authors declare no known competing financial interests (PubMed).

    PubMed 42603384DOI

  5. RodentJ Chromatogr B Analyt Technol Biomed Life Sci 2026

    LC-MS/MS quantitation of tirzepatide in rat plasma, and its plasma kinetics in rats

    Design
    LC-MS/MS method development and validation, applied to a pharmacokinetic study in rats
    Population or model
    rat plasma
    Molecule
    Tirzepatide (LY3298176) exact

    The authors declare no known competing financial interests (PubMed).

    PubMed 41197390DOI

  6. Human, uncontrolledEur J Pharm Sci 2024

    Excretion, circulating metabolites and metabolic pathways of radiolabelled tirzepatide in humans, rats and monkeys

    Design
    Radiolabel ([14C]) absorption, distribution, metabolism and excretion study in healthy men, rats and cynomolgus monkeys
    Population or model
    healthy male participants; Sprague Dawley and Long Evans rats; cynomolgus monkeys
    Molecule
    Tirzepatide (LY3298176) exact
    Blinding
    open (single arm)

    Authors are employees and shareholders of Eli Lilly and Company (PubMed).

    PubMed 39243911DOI

  7. Human, uncontrolledClin Pharmacokinet 2021

    Plasma pharmacokinetics (AUC and Cmax) of tirzepatide by renal function group

    Design
    Phase 1, parallel group pharmacokinetic study by renal function group
    Population or model
    adults grouped by renal function, including end-stage renal disease, and adults with normal renal function
    Molecule
    Tirzepatide (LY3298176) exact
    n
    45
    Comparator
    normal renal function group
    Funding
    Eli Lilly and Company

    Authors are employees and shareholders of Eli Lilly and Company (PubMed).

    PubMed 33778934DOI

  8. Human, uncontrolledClin Pharmacokinet 2022

    Plasma pharmacokinetics (AUC and Cmax) of tirzepatide by hepatic function group

    Design
    Phase 1, parallel group, open label pharmacokinetic study by hepatic function group
    Population or model
    adults with mild, moderate or severe hepatic impairment (Child-Pugh A, B, C) and adults with normal hepatic function
    Molecule
    Tirzepatide (LY3298176) exact
    n
    32
    Comparator
    normal hepatic function group
    Blinding
    open label
    Funding
    Eli Lilly and Company

    Authors are employees and shareholders of Eli Lilly and Company (PubMed).

    PubMed 35674880DOI

  9. RodentiScience 2026

    Kidney fibrosis and inflammation pathway markers in HK-2 cells and in mouse kidney injury and ageing models, comparing semaglutide, tirzepatide and retatrutide

    Design
    Comparison of three agonists in a human kidney cell line and in mouse models of kidney injury and ageing
    Population or model
    HK-2 cells; mice with unilateral ureteral obstruction (UUO); aged mice
    Molecule
    Tirzepatide (LY3298176) exact
    Comparator
    semaglutide and retatrutide

    The authors declare no competing interests (PubMed).

    PubMed 42630988DOI

  10. Human, randomisedN Engl J Med 2025

    Composite of cardiovascular death, myocardial infarction or stroke, tirzepatide compared with dulaglutide (noninferiority design)

    Design
    Phase 3, randomised 1:1, double-blind, active comparator noninferiority trial (SURPASS-CVOT)
    Population or model
    adults with atherosclerotic cardiovascular disease, eligibility as registered in NCT04255433
    Molecule
    Tirzepatide (LY3298176) exact
    n
    13299
    Comparator
    dulaglutide
    Blinding
    double-blind
    Funding
    Eli Lilly

    Funded by Eli Lilly (abstract).

    PubMed 41406444DOIcomment exchange: PubMed CommentIn (6)

Receptor pharmacology studied

  • In receptor binding studies, tirzepatide bound the GIP receptor with an affinity comparable to native GIP and the GLP-1 receptor about 5-fold more weakly than native GLP-1; it stimulated cAMP accumulation through both receptors in cell lines. Source sentenceIn receptor binding studies, LY3298176 binds either receptor with high affinity ... the affinity is comparable to native GIP for the GIPR and approximately 5-fold weaker than native GLP-1 for the GLP-1R ... In signaling studies using cell lines with recombinantly expressed GIPR or GLP-1R, LY3298176 potently stimulates cAMP accumulation by either receptor1 Mol Metab 2018
  • Receptor occupancy estimates in the 2020 pharmacology paper show greater engagement of the GIP receptor than of the GLP-1 receptor; the authors call the profile imbalanced and biased. Source sentenceThis analysis reveals a greater degree of engagement of tirzepatide for the GIP receptor than the GLP-1 receptor, corroborating an imbalanced mechanism of action.2 JCI Insight 2020
  • The same paper reports a weaker ability than GLP-1 to drive GLP-1 receptor internalisation. Source sentencecoincident with a weaker ability to drive GLP-1 receptor internalization compared with GLP-12 JCI Insight 2020
  • Cryo-electron microscopy structures of tirzepatide bound to the GIP receptor and to the GLP-1 receptor were published in 2022. Source sentencewe determine cryo-electron microscopy structures of tirzepatide-bound GIPR and GLP-1R as well as peptide 20-bound GIPR, GLP-1R and GCGR4 Nat Commun 2022

Status matrix

European Union: EMA records

EU

  • On 3 Sep 2025 EMA and the Heads of Medicines Agencies warned about illegal medicines sold online as GLP-1 receptor agonists, naming tirzepatide with semaglutide and liraglutide, and stated that such products are not authorised. Source sentence3 September 2025 ... In recent months there has been a sharp rise in the number of illegal medicines marketed as GLP-1 receptor agonists such as semaglutide, liraglutide and tirzepatide ... These products, often sold via fraudulent websites and promoted on social media, are not authorised33 EMA and HMA statement, 3 September 2025

United Kingdom: MHRA records

UK

  • On 24 Feb 2026 the MHRA reported falsified pens presented as an authorised tirzepatide medicine and supplied through one online pharmacy; it stated that testing confirmed the pens contain tirzepatide but that sterility could not be confirmed. Source sentenceGOV.UK news story, 24 Feb 2026: [a] fake [medicine] (tirzepatide) KwikPen ... from The Private Pharmacy Clinic in Birmingham ... "Testing has confirmed that the identified fake pens do contain tirzepatide, the active substance in [the medicine], but because the manufacturing conditions are unknown, we cannot confirm that the contents are sterile."28 GOV.UK search for tirzepatide (MHRA items), 14 October 2026

Sport anti-doping list

International

  • The WADA 2026 Prohibited List does not name tirzepatide or LY3298176 (text search of the list on 14 Oct 2026). Source sentenceNo match for tirzepatide or LY3298176 in the full text of the 2026 list; "This List shall come into effect on 1 January 2026."32 WADA Prohibited List 2026

Registered trials

  • NCT04255433Phase 3

    Status
    Completed (start 29 May 2020, primary completion 12 Jun 2025); results posted on the registry
    Sponsor
    Eli Lilly and Company
    Site countries
    Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Czechia, France, Germany, Greece, Hungary, India, Israel, Italy, Japan, Mexico, Netherlands, Poland, Puerto Rico, Romania, Russia, Slovakia, South Korea, Spain, Sweden, Taiwan, Türkiye, Ukraine, UK, US
    Primary endpoint
    composite of cardiovascular death, myocardial infarction or stroke, noninferiority against dulaglutide
    Primary endpoint met
    met
    Last synced
    14 October 2026

  • NCT04311424Phase 1

    Status
    Completed (start 28 Jul 2020, primary completion 2 Oct 2020); results posted on the registry
    Sponsor
    Eli Lilly and Company
    Site countries
    UK
    Primary endpoint
    excretion of radioactivity in urine and faeces over time (descriptive, no met or not met test)
    Primary endpoint met
    not reported
    Last synced
    14 October 2026

Timeline

  1. Phase 1 study NCT02759107 of LY3298176 starts, in healthy participants and a patient cohort Source sentencestartDateStruct 2016-05-11 (ACTUAL); briefTitle: A Study of Tirzepatide (LY3298176) in Healthy Participants and Participants With ...36 NCT02759107
  2. Discovery report and phase 1 results for LY3298176 published Source sentenceMol Metab 2018 Dec; PubMed publication types: Clinical Trial, Phase I; Randomized Controlled Trial1 Mol Metab 2018
  3. Receptor pharmacology paper describes tirzepatide as imbalanced and biased Source sentenceJCI Insight 2020 Sep 32 JCI Insight 2020
  4. Cryo-EM structures of tirzepatide bound to the GIP and GLP-1 receptors published Source sentenceNat Commun 2022 Feb 254 Nat Commun 2022
  5. Radiolabel absorption, distribution, metabolism and excretion study in humans, rats and monkeys published Source sentenceEur J Pharm Sci 2024 Nov 15 Eur J Pharm Sci 2024
  6. SURPASS-CVOT, a phase 3 noninferiority trial against dulaglutide with a cardiovascular composite endpoint, published Source sentenceN Engl J Med 2025; "We conducted an active-comparator-controlled, double-blind, noninferiority trial"26 N Engl J Med 2025
  7. LC-HRMS method for nine GLP-1 receptor agonist peptides, including tirzepatide, published Source sentenceJ Chromatogr A 2026 Oct 1124 J Chromatogr A 2026

Integrity notes

Chemistry and records

Tirzepatide: sequence, mass, CAS and regulatory record in the research library →

Sources

  1. 1Mol Metab 2018 accessed 14 Oct 2026
  2. 2JCI Insight 2020 accessed 14 Oct 2026
  3. 3PubChem CID 166567236 accessed 14 Oct 2026
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About this page

Research-use information. This library summarises published literature and regulator records. It is not guidance for use, not medical advice, and not a statement that any material is suitable for use in people or animals.

Reviewed by the Peptency editorial process. Version 1, last edited 14 October 2026, 36 sources.

Cite this page: Peptency Academy. Tirzepatide: chemistry, receptor studies, trials and status. Version 1./eu/academy/compounds/tirzepatide/