Retatrutide, development code LY3437943, is a synthetic peptide that activates three receptors at once: GLP-1, GIP and glucagon. That combination is what makes it distinctive, and it is worth understanding why a third target was added rather than treating it as simply “the newer one”.
The progression from one receptor to three
Incretin research has moved through three generations of receptor targeting:
- Single agonists act at the GLP-1 receptor alone. Semaglutide and liraglutide sit here.
- Dual agonists add the GIP receptor. Tirzepatide is the widely studied example.
- Triple agonists add the glucagon receptor. Retatrutide is the most studied compound in this class.
The glucagon receptor is the interesting addition, because glucagon has historically been thought of as opposing insulin — raising blood glucose rather than lowering it. Adding glucagon receptor activity to a compound intended to improve metabolic parameters looks counterintuitive at first glance.
The rationale is that glucagon receptor activation increases energy expenditure and affects hepatic lipid handling, effects distinct from its action on glucose. In a molecule that also carries strong GLP-1 and GIP activity, the theory is that the incretin arms offset the glycaemic effect while the glucagon arm contributes on the energy expenditure side. Whether that balance behaves as designed is precisely what the research is investigating.
Unimolecular design
Retatrutide is a unimolecular triple agonist: a single peptide chain that binds all three receptors, rather than a combination of three separate drugs. This matters for research design. A single molecule has one pharmacokinetic profile, so the three activities cannot drift apart in time the way a three-drug combination can. It also means the ratio of activity at the three receptors is fixed by the molecule's structure and cannot be adjusted independently.
That fixed ratio is a design decision baked into the sequence, and it is one of the variables that distinguishes compounds in this class from one another.
The published trials
Three Phase 2 studies form the bulk of the peer-reviewed record. We list them because the primary literature is more useful than any summary of it:
- Jastreboff AM, et al. New England Journal of Medicine, 2023. PMID 37366315 — Phase 2 randomised trial in obesity.
- Rosenstock J, Frías J, Jastreboff AM, et al. The Lancet, 2023. PMID 37385280 — Phase 2 trial in type 2 diabetes.
- Sanyal AJ, et al. Nature Medicine, 2024. PMID 38858523 — Phase 2a trial in metabolic dysfunction-associated steatotic liver disease.
All three are Phase 2. Retatrutide is an investigational compound; it is not an approved medicine in the UK or anywhere else, and the trial results above are findings in defined study populations rather than general conclusions.
What this means for handling it in the laboratory
Two practical points follow from the chemistry rather than the pharmacology.
It is a large peptide. The molecular formula is C₂₂₁H₃₄₂N₄₆O₆₈, which puts it well above the mass of the short peptides many laboratories are used to handling. Larger peptides carry proportionally more counter-ion, so the gap between the mass of solid in the vial and the mass of peptide in the vial is worth attending to — the reasoning is set out in HPLC purity versus net peptide content.
Vial concentrations run high. A 20 mg vial reconstituted with 3 mL gives roughly 6,667 mcg/mL. At that concentration, small target quantities correspond to very small volumes, and a figure below about two units on a U-100 syringe cannot be measured reliably. Our reconstitution calculator flags this automatically and shows what a different water volume would do.
Storage
As supplied, lyophilised and stored at −20 °C protected from light and moisture. Once reconstituted, refrigerated at 4 °C, used within a few weeks, and not refrozen. Repeated freeze-thaw cycles degrade peptide integrity and are a common source of inconsistent results between runs. Full guidance is in our Reconstitution & Storage guide.
What we supply
Retatrutide 20mg is supplied as a lyophilised powder, HPLC verified by our supplier to a 99%+ purity standard, with CAS number 2381089-83-2 and full specifications on the product page. Bacteriostatic water for reconstitution is available separately.
Retatrutide is supplied by ASPeptides for in vitro laboratory research use only. It is not a medicinal product, is not approved for human or veterinary use, and nothing on this page constitutes medical advice or a recommendation for use in humans. Published studies are cited for scientific context only.