Tirzepatide

Classification

Dual GIP and GLP-1 receptor agonist

Approval status

Approved medicine

Research status

Approved dual incretin agonist for type 2 diabetes and, in some markets/brands, chronic weight management.

Molecular formula

C225H348N48O68

Molecular weight

4813.5 g·mol⁻¹ (approximate; salt forms vary)

Sequence

Acylated dual GIP/GLP-1 receptor agonist peptide; residue map is in product information.

Primary biological target

GIP receptor and GLP-1 receptor

Half-life

Approximately 5 days (supports once-weekly subcutaneous dosing in labelled products)

Routes investigated

Subcutaneous

Human evidence level

A — Approved clinical use / strong human evidence

A prescription peptide medicine for type 2 diabetes and, in some markets and brands, chronic weight management. It is not sold as a research chemical or cosmetic.

Synthetic peptide engineered from a GIP backbone with dual GIP and GLP-1 activity and a fatty-acid moiety for extended duration.

Established (labelled / textbook receptor pharmacology)

Tirzepatide is a dual agonist at glucose-dependent insulinotropic polypeptide (GIP) receptors and GLP-1 receptors. Combined incretin-receptor activity affects insulin secretion, glucagon, gastric emptying and appetite. The dual pharmacology is distinct from single GLP-1 agonists. Fine mapping of which receptor contributes which clinical effect is still being studied; the approved indications rest on Phase 3 programmes, not on incomplete receptor-attribution models.

In labelled populations it can substantially improve glycaemic control and body weight under medical supervision.

• Type 2 diabetes

  A · Approved clinical use / strong human evidence

  SURPASS Phase 3 trials have investigated glycaemic control versus comparators.^[2]

• Obesity / weight management

  A · Approved clinical use / strong human evidence

  SURMOUNT-1 investigated once-weekly tirzepatide for weight reduction in adults with obesity.^[1]

Investigational findings are not proven clinical benefits unless an authority has labelled that indication.

Overall human evidence grade: A · Approved clinical use / strong human evidence

Animal, cell and in-vitro findings are listed separately from human effects.

• In-vitro / translational: Cellular dual-receptor pharmacology

  The molecule shows activity at both GIP and GLP-1 receptors. Proposed mechanism details of tissue contribution should be labelled as still under study where not in the PI.

  Limitations: Receptor profiles do not equal unapproved indications.

  ^[1]

This section does not provide personalised medical dosing. Values are those reported in papers or protocols. Animal mg/kg doses are not converted to human doses.

Doses reported in human studies

1. SURMOUNT-1

   Dose: 5, 10 or 15 mg

   Route: Subcutaneous

   Frequency: Once weekly

   Duration: 72 weeks

   Population: Adults with obesity

   Purpose: Weight-management efficacy

   ^[1]

Preclinical / animal study dosing

Insufficient reliable evidence identified.

Taken from regulator product information. This is not mixed with research-chemical schedules.

• FDA · United States

  Mounjaro / Zepbound (tirzepatide) — brand depends on indication

  Indication: Type 2 diabetes (Mounjaro) and chronic weight management (Zepbound) as labelled

  Regimen: Once-weekly subcutaneous injection after labelled escalation to 5, 10 or 15 mg (confirm current USPI).

  FDA Prescribing Information — tirzepatide products

• TGA · Australia

  ARTG-registered tirzepatide presentations

  Indication: As per current Australian PI

  Regimen: Follow the Australian Product Information for the registered brand.

  TGA Product Information

Half-life

~5 days

Metabolism

Proteolytic degradation of the peptide backbone

Use the current PI for Cmax/Tmax tables.

Gastrointestinal events predominate (nausea, diarrhoea, vomiting, constipation).

Serious events. Class discussions include pancreatitis, gallbladder disease, hypoglycaemia with insulin/secretagogues, and thyroid C-cell tumour warning in US labels (rodent findings).

Pregnancy / lactation. Not recommended; see PI.

Unknowns. Unregulated compounded dual-agonist products are not equivalent to labelled tirzepatide.

Contraindications. Similar class cautions to other incretin mimetics, including MEN2/MTC history where listed. Prescription-only; not for compounding as a ‘research peptide’.

Australia — TGA

Prescription medicine where registered; indication-specific. Not sold here.

United States — FDA

Approved as separate branded products for diabetes and weight management.

European Union — EMA

Authorised products exist; read the SmPC for the exact name and indication.

1. [1] Tirzepatide Once Weekly for the Treatment of Obesity

   Jastreboff AM et al. Tirzepatide Once Weekly for the Treatment of Obesity N Engl J Med. 2022. doi:10.1056/NEJMoa2206038 PMID 35658024

   PMID 35658024DOI

2. [2] Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes

   Frías JP et al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes N Engl J Med. 2021. doi:10.1056/NEJMoa2107519 PMID 34170647

   PMID 34170647DOI