Regulated as medicinal products

Tirzepatide

Last reviewed

Reviewed by HelixEvoLabs Research Team

Technical, analytical and regulatory reference for tirzepatide as a manufactured synthetic peptide material.

Identity and nomenclature

INN
tirzepatide
Synonyms
Mounjaro, Zepbound
Development codes
LY3298176

Mechanism

Tirzepatide is a synthetic 39-residue acylated peptide acting as an agonist at both the glucose-dependent insulinotropic polypeptide (GIP) receptor and the glucagon-like peptide-1 receptor. Its peptide component is based on the GIP sequence.

The assessment report records that the peptide component is based on the GIP sequence and contains two non-coded 2-aminoisobutyric acid residues at positions 2 and 13, a C-terminal amide, and acylation at Lys20.

Higher-order structure was characterised by orthogonal biophysical techniques, and the secondary structure is recorded as predominantly alpha-helical under native conditions. A cell-based bioassay forms one of three orthogonal identity tests on the drug substance.

Analytical and manufacturing profile

Analytical data sheet

Tirzepatide

Identity

Molecular formula
C225H348N48O68
Molecular weight
4813.45 g/mol (average); 4810.52 Da (monoisotopic)
CAS number
2023788-19-2
UNII
OYN3CCI6QE
Chemical name
L-Serinamide, L-tyrosyl-2-methylalanyl-L-α-glutamylglycyl-L-threonyl-L-phenylalanyl-L-threonyl-L-seryl-L-α-aspartyl-L-tyrosyl-L-seryl-L-isoleucyl-2-methylalanyl-L-leucyl-L-α-aspartyl-L-lysyl-L-isoleucyl-L-alanyl-L-glutaminyl-N6-[(22S)-22,42-dicarboxy-1,10,19,24-tetraoxo-3,6,12,15-tetraoxa-9,18,23-triazadotetracont-1-yl]-L-lysyl-L-alanyl-L-phenylalanyl-L-valyl-L-glutaminyl-L-tryptophyl-L-leucyl-L-isoleucyl-L-alanylglycylglycyl-L-prolyl-L-seryl-L-serylglycyl-L-alanyl-L-prolyl-L-prolyl-L-prolyl
Appearance
Hygroscopic white to practically white solid

Primary structure

YAEGTFTSDYSIALDKIAQKAFVQWLIAGGPSSGAPPPS

39 residues

Modifications

  • The sequence above is transliterated from the systematic chemical name recorded in the assessment report rather than quoted from a nomenclature authority, and should be confirmed against the WHO INN list before publication.
  • Positions 2 and 13 are 2-aminoisobutyric acid. The one-letter sequence encodes both as A, so a plain copy of the one-letter string loses both substitutions.
  • The C-terminus is an amide, recorded in the systematic name as L-serinamide.
  • The Lys20 residue is attached to 1,20-eicosanedioic acid via a linker consisting of one gamma-glutamic acid and two 8-amino-3,6-dioxaoctanoic acid units. Retatrutide carries one such unit rather than two, and the two architectures are easily confused.
  • All natural amino acids are in the L form. Glycine is achiral and the 2-aminoisobutyric acid residues at positions 2 and 13 have no chiral centre. Configuration is controlled by chiral gas chromatography-mass spectrometry in the characterisation package.
  • Manufactured by solid-phase peptide synthesis at a single site. The linear side chain is added on-resin at Lys20, the peptide is cleaved from the resin with simultaneous side-chain deprotection, and the crude substance is purified by reversed-phase chromatography, concentrated, solvent exchanged, isolated and dried. This differs fundamentally from the recombinant route used for semaglutide, and the impurity control strategy follows ICH Q3A for new chemical entities rather than a biotechnology framework.
  • The Global Substance Registration System record publishes the formula C225H347O66N49 against this UNII, which disagrees with the C225H348N48O68 stated in both the European assessment report and the United States prescribing information on nitrogen, oxygen and hydrogen count alike. Two independent regulatory sources agree with each other and the substance registry does not, so the label formula is the one recorded here. The same registry is known to publish estimated formulas for compounds in this class, and a formula taken from it should be checked against a label before use.
  • Average molecular weight is stated as 4813.45 g/mol in the European assessment report and 4813.53 Da in the United States prescribing information. The 0.08 difference reflects the atomic weight set and rounding convention each applied, not a difference in the substance. A specification quoting either figure to two decimal places is quoting a convention as though it were a measurement.

Solubility

5 mM phosphate buffer, pH 7.0, 25 °C
Freely soluble. This is the only named solvent for which a solubility descriptor is published, and freely soluble is the pharmacopoeial descriptive term

Storage

FormTemperatureDuration
Active substanceFrozen, -25 °C to -10 °CRetest period justified by stability data; the period itself is not published
Solution for injection, finished product2-8 °C. Do not freeze2 years
Solution for injection, unrefrigerated excursionNot above 30 °CUp to 21 days

Stability

  • The drug substance is stored frozen while the finished product must not be frozen. This asymmetry is explicit in the assessment report and is easy to get wrong when transferring handling instructions between the two.
  • The finished product in the semi-finished syringe is susceptible to degradation under ICH Q1B confirmatory photostability conditions. Degradation was reduced when the product was incorporated into the autoinjector, and no degradation was observed for autoinjectors in the marketing pack. Light protection is therefore delivered by packaging rather than by the molecule.
  • No degradation was observed under the proposed storage conditions for the active substance. Under stress at 25 degrees Celsius and 60 per cent relative humidity for six months, impurities increased with a corresponding decrease in purity, consistent with the degradation pathways characterised in stress studies.
  • Polymorphism has not been observed for the active substance.
  • A forced-degradation study reports 15.9 to 19.0 per cent degradation across acidic, basic, oxidative, thermal and photolytic stress. The photolytic condition in that study was direct sunlight, which is not an ICH Q1B compliant condition and should not be presented as one.

Analytical methods

MethodPurposeSpecification
RP-LC-UVDrug substance and finished product: identification by retention, assay, and purity. One of three orthogonal drug-substance identity testsNot verified
Peptide mappingPrimary-structure identity on both drug substance and finished product; the second of the orthogonal identity testsNot verified
Cell-based bioassayFunctional identity on the drug substance; the third orthogonal identity testNot verified
RP-LC-MSPurity by a second, orthogonal detection principle alongside ultraviolet detectionNot verified
SECHigh molecular weight species on drug substance and finished productNot verified
GCResidual solvents on the drug substance, relevant given the solid-phase synthesis routeNot verified
Chiral GC-MSAmino acid configuration in the characterisation package; the racemisation control for a synthetic peptideNot verified
Water content, bacterial endotoxins, TAMC and TCYMC (Ph. Eur.)Drug substance release tests by pharmacopoeial methodsNot verified
CG-MALSComposition gradient multi-angle light scattering, used in structural characterisation to probe oligomeric state and self-associationNot verified
Far-UV and near-UV circular dichroism, FT-IR, NMRHigher-order and secondary structure characterisation; secondary structure recorded as predominantly alpha-helical under native conditionsNot verified
Ion chromatographyCounter-ion and ionic species determination in structural characterisationNot verified
ICP-MSElemental impurities. Batch data showed no relevant elemental impurity above 30 per cent of its permitted daily exposure, so no routine control was required under ICH Q3DNot verified
Sterility, particulate matter, pH, osmolality (Ph. Eur.)Finished-product release tests for a sterile parenteral solutionNot verified

Impurities and degradation products

  • No individual impurity or degradation product is named in the public assessment record. The report states that degradation pathways were discussed in detail and most degradation products identified for both solid active substance and solution, but does not publish their identities.
  • The drug-substance impurity specification is structured as total, specified, and largest unspecified. The numeric limits are withheld as commercially confidential, so no limit should be quoted for this compound.
  • Impurities above the ICH Q3A qualification threshold were qualified by toxicological and clinical studies. The finished-product manufacturing process does not introduce new degradation products relative to the active substance.
  • A nitrosamine risk assessment concluded there is no risk of nitrosamine impurities in either the active substance or the finished product.

Handling

  • The drug substance is hygroscopic, which implies moisture-protective handling, and is stored frozen between -25 and -10 degrees Celsius.
  • The finished product requires light protection, delivered by the autoinjector and marketing pack rather than by the molecule, and must not be frozen.
  • No excipients of animal or human origin are used. No occupational exposure limit or personal protective equipment guidance is published in any acceptable source, so containment is set by the receiving facility under its own assessment.

Clinical development

SURMOUNT-1

NCT04184622
Phase
3
Enrolment
2539
Duration
72 weeks
Status
reported
Population
Adults with obesity, or overweight with at least one weight-related comorbidity, without diabetes
Primary endpoint
Percentage change from baseline in body weight at week 72, and proportion of participants achieving a body weight reduction of 5 per cent or more

Reported outcomes

Outcomes as reported by SURMOUNT-1, attributed to trial arm and timepoint
MetricArmValueComparatorTimepoint
Percentage change from baseline in body weight (efficacy estimand)Tirzepatide 5 mg once weekly, subcutaneous-16.0% (SE 0.39)Placebo -2.4% (SE 0.40)Week 72
Percentage change from baseline in body weight (efficacy estimand)Tirzepatide 10 mg once weekly, subcutaneous-21.4% (SE 0.39)Placebo -2.4% (SE 0.40)Week 72
Percentage change from baseline in body weight (efficacy estimand)Tirzepatide 15 mg once weekly, subcutaneous-22.5% (SE 0.39)Placebo -2.4% (SE 0.40)Week 72
Proportion achieving body weight reduction of 5 per cent or moreTirzepatide 15 mg once weekly, subcutaneous96.32%Placebo 27.87%Week 72
Onset of type 2 diabetes, obesity with prediabetes subsetTirzepatide, all doses pooled1.3%; hazard ratio 0.07, 95% CI 0.0 to 0.1Placebo 13.3%Week 176

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

Sponsor Eli Lilly and Company · New England Journal of Medicine, 2022 · doi:10.1056/NEJMoa2206038 · PMID 35658024 · verified 2026-07-30

SURPASS-2

NCT03987919
Phase
3
Enrolment
1879
Duration
40 weeks
Status
reported
Population
Adults with type 2 diabetes inadequately controlled on metformin, with glycated haemoglobin between 7.0 and 10.5 per cent and body mass index of at least 25
Primary endpoint
Change from baseline in glycated haemoglobin at week 40, for the 10 mg and 15 mg arms

Reported outcomes

Outcomes as reported by SURPASS-2, attributed to trial arm and timepoint
MetricArmValueComparatorTimepoint
Change from baseline in glycated haemoglobin (efficacy estimand)Tirzepatide 10 mg once weekly, subcutaneous-2.37 percentage points (SE 0.048)Semaglutide 1 mg once weekly -1.86 percentage points (SE 0.048)Week 40
Change from baseline in glycated haemoglobin (efficacy estimand)Tirzepatide 15 mg once weekly, subcutaneous-2.46 percentage points (SE 0.048)Semaglutide 1 mg once weekly -1.86 percentage pointsWeek 40
Change from baseline in body weight (efficacy estimand)Tirzepatide 15 mg once weekly, subcutaneous-12.4 kg (SE 0.34); difference -6.2 kg, 95% CI -7.1 to -5.3Semaglutide 1 mg once weekly -6.2 kg (SE 0.33)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 · New England Journal of Medicine, 2021 · doi:10.1056/NEJMoa2107519 · PMID 34170647 · verified 2026-07-30

Regulatory status by jurisdiction

  • European Union

    European Medicines Agency
    Approved medicine

    Authorised under a single marketing authorisation covering two distinct indications. The paediatric reach applies to the diabetes indication only; the weight-management indication is for adults.

    Mounjaro EPAR product information, Annex IVerified 2026-07-30

  • United Kingdom

    MHRA
    Approved medicine

    Authorised under a single brand across pen, vial and multi-dose pen presentations. The indication is constructed differently from the EU text, using a numbered format and reordering the weight-management clause, so the two are not interchangeable as quoted wording.

    MHRA products database, tirzepatide summaries of product characteristicsVerified 2026-07-30

  • United States

    FDA
    Approved medicine

    Approved under two separate new drug applications carrying different brand names, rather than the single authorisation covering both indications used in the EU and UK. Mounjaro under NDA 215866 covers type 2 diabetes; Zepbound under NDA 217806 covers weight management and obstructive sleep apnoea. The United States authorised tirzepatide first, four months ahead of the European Union.

    Zepbound (tirzepatide) US prescribing informationVerified 2026-08-05

Supply classification and permitted use

Tirzepatide is an approved medicinal product in multiple jurisdictions. HelixEVO does not supply medicinal products for human administration. Material is supplied to businesses for research and manufacturing purposes only.

  • Authorised indications differ by jurisdiction, and the brand structure differs: the European Union and the United Kingdom carry both indications under a single brand, whereas the United States divides them across two brands.
  • The FDA has issued warning letters concerning unapproved products containing tirzepatide that were labelled for research purposes or not for human consumption.
  • Supply of material does not constitute authorisation to place a finished medicinal product on any market.

How supply classifications work · Documented safety signals

References

  1. [1]RegulatorAssessment report — Mounjaro (tirzepatide), EMA/791310/2022 — European Medicines Agency, 2022 · accessed
  2. [2]RegulatorMounjaro EPAR product information, Annex I summary of product characteristics — European Medicines Agency, 2026 · accessed
  3. [3]RegulatorZEPBOUND (tirzepatide) injection, for subcutaneous use — US prescribing information — Eli Lilly and Company, via DailyMed (US National Library of Medicine), 2026 · accessed
  4. [4]RegulatorMOUNJARO (tirzepatide) injection, for subcutaneous use — US prescribing information — Eli Lilly and Company, via DailyMed (US National Library of Medicine), 2026 · accessed
  5. [5]RegulatorDrugs@FDA application records for tirzepatide: NDA 215866 (Mounjaro) and NDA 217806 (Zepbound) — US Food and Drug Administration, 2026 · accessed
  6. [6]RegulatorTIRZEPATIDE — Global Substance Registration System record, UNII OYN3CCI6QE — Global Substance Registration System (NIH/NCATS), 2026 · accessed
  7. [7]RegulatorMHRA products database, tirzepatide summaries of product characteristics — Medicines and Healthcare products Regulatory Agency, 2026 · accessed
  8. [8]Peer-reviewedKhalil HA, Hassanein NA, El-Yazbi AF, Mahgoub H. A multimodal HPLC stability indicating approach for the estimation of semaglutide and tirzepatide in bulk, pharmaceutical dosage forms, and rat plasma — Springer, BMC Chemistry, 2026 · doi:10.1186/s13065-025-01716-7 · accessed