Retatrutide

Classification

Triple GIP/GLP-1/glucagon receptor agonist (investigational)

Approval status

Investigational · Not approved for human use

Research status

Investigational triple agonist. Not an approved medicine at last review of this encyclopaedia page.

Molecular formula

Insufficient reliable evidence identified.

Molecular weight

Insufficient reliable evidence identified.

Sequence

Engineered peptide with activity at three metabolic receptors; fatty-acid modification for duration.

Primary biological target

GLP-1, GIP and glucagon receptors (triple agonist)

Half-life

Supports once-weekly subcutaneous dosing in published Phase 2 protocols

Routes investigated

Subcutaneous

Human evidence level

B — Multiple human clinical studies

An investigational obesity/diabetes peptide — not an approved Australian medicine and not sold by this shop.

Synthetic peptide designed for simultaneous GLP-1, GIP and glucagon receptor activity.

Proposed mechanism

Proposed mechanism: retatrutide is described in clinical literature as a triple agonist at GLP-1, GIP and glucagon receptors. Downstream effects on appetite, glycaemia and energy expenditure are inferred from this pharmacology and from Phase 2 weight and metabolic endpoints. Mechanism not yet fully established as a labelled drug, because no approved PI existed at last review.

Would be expected to affect appetite, glycaemia and energy expenditure if used as a registered drug — it is not one here.

• Obesity

  B · Multiple human clinical studies

  A Phase 2 randomised trial has investigated once-weekly retatrutide for obesity.^[1]

• Type 2 diabetes

  B · Multiple human clinical studies

  Early human research has examined glycaemic and weight endpoints in type 2 diabetes.^[1]

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

Overall human evidence grade: B · Multiple human clinical studies

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

Triple-agonist animal models exist.

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. Jastreboff et al. Phase 2 obesity trial

   Dose: 1–12 (dose-ranging groups) mg

   Route: Subcutaneous

   Frequency: Once weekly

   Duration: 48 weeks

   Population: Adults with obesity

   Purpose: Efficacy and safety in obesity

   ^[1]

Preclinical / animal study dosing

Insufficient reliable evidence identified.

Published Phase 2 protocols used once-weekly injection; full PK tables belong in the primary paper and any future PI.

Gastrointestinal events similar to other incretin agonists were reported.

Unknowns. Long-term and regulatory-review safety package is not equivalent to an approved product.

Contraindications. Not for human use outside trials / licensed products.

Australia — TGA

Not approved.

United States — FDA

Investigational (not approved at last encyclopaedia review).

European Union — EMA

Not approved.

1. [1] Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial

   Jastreboff AM et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial N Engl J Med. 2023. doi:10.1056/NEJMoa2301972 PMID 37366315

   PMID 37366315DOI