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Research use only
· 7 min read
Most research peptides are built to hit one receptor. Retatrutide (developer code LY3437943) hits three - GIP, GLP-1 and glucagon - from a single engineered molecule, which is either elegant design or showing off depending on which pharmacologist you ask. This is a research-context guide to what that triple-agonist label actually rests on: the molecular identity, the receptor mechanism studies have resolved, the registered trial programme, and how it differs from tirzepatide and semaglutide. Everything below describes what published studies have investigated, not any human use.
| Compound | Retatrutide (developer code LY3437943) |
|---|---|
| Class | Triple GIP / GLP-1 / glucagon receptor agonist |
| Originator | Eli Lilly |
| Molecular formula | C221H342N46O68 |
| Molecular weight | Approximately 4731 g/mol |
| CAS number | 2381089-83-2 |
| PubChem CID | 171390338 (sodium-salt record 171934787) |
Retatrutide came out of Eli Lilly, and the peer-reviewed discovery paper (Coskun et al., Cell Metabolism, 2022) is where the triple-agonist claim originates. It characterises a single molecule that engages three class B G-protein-coupled receptors at once: the glucagon receptor (GCGR), the glucose-dependent insulinotropic polypeptide receptor (GIPR) and the glucagon-like peptide-1 receptor (GLP-1R). One molecule, three locks.
On paper it belongs to the GLP-1 superfamily, but its backbone is borrowed from GIP, not GLP-1 - a lineage detail that quietly undercuts the shorthand that files it as just a stronger GLP-1 peptide. PubChem indexes it with the molecular formula C221H342N46O68 and a molecular weight of approximately 4731 g/mol (PubChem CID 171390338; a separate sodium-salt record sits at CID 171934787), and chemistry suppliers list the free-form CAS number as 2381089-83-2. Structurally it is a 39-residue sequence on that GIP backbone, lipidated through a fatty-diacid linker at lysine 17 to support albumin binding. Kovalabs supplies retatrutide strictly as a research reagent.
There is a small irony buried in the naming. Retatrutide gets filed under GLP-1, but in the in-vitro assays reported by the originating laboratory it was most potent at the GIP receptor, with GLP-1R and GCGR trailing. A 2025 review (Katsi et al., Biomolecules, 2025) put the reported half-maximal effective concentrations at roughly 0.064 nM at the GIP receptor, 0.78 nM at the GLP-1 receptor and 5.8 nM at the glucagon receptor - a clean potency ordering of GIP over GLP-1 over glucagon that spans about two orders of magnitude. The same literature reports an elimination half-life of approximately six days.
Binding assays show that one sequence hits three receptors; they do not show how it manages the trick. That part was resolved by an independent cryo-electron-microscopy study (Li et al., Cell Discovery, 2024), which determined the structures of retatrutide bound to each of GLP-1R, GIPR and GCGR. The peptide keeps a common set of contacts with conserved receptor residues while accommodating receptor-specific residues in the upper transmembrane pocket, with the largest differences at extracellular loops 1 and 3 (for example, GIPR extracellular loop 1 adopting an unwound, relaxed conformation). That structural account, not the binding numbers alone, is the strongest evidence behind the triple-agonist label.
The three get lumped together as if they were one idea at three strengths. The published structural pharmacology says otherwise, and the cleanest way to separate them is to count receptors. Semaglutide is a GLP-1 receptor mono-agonist developed by Novo Nordisk (Lau et al., Journal of Medicinal Chemistry, 2015). Tirzepatide is a dual agonist of the GIP and GLP-1 receptors, with no glucagon-receptor arm (Sun et al., PNAS, 2022). Retatrutide adds exactly that missing third arm, and that added GCGR activity is the single mechanistic feature most often cited to distinguish it from tirzepatide. A separate research branch reached the glucagon receptor from the other direction, pairing GCGR and GLP-1 agonism without the GIP arm, as studied for survodutide (le Roux et al., The Lancet Diabetes and Endocrinology, 2024).
| Compound | Receptor targets | Originator | Peptide backbone |
|---|---|---|---|
| Semaglutide | GLP-1 | Novo Nordisk | GLP-1 |
| Tirzepatide | GIP + GLP-1 | Eli Lilly | GIP |
| Retatrutide | GIP + GLP-1 + glucagon | Eli Lilly | GIP |
The compounds also differ in molecular lineage. Semaglutide is built on a GLP-1 backbone, a 31-residue analogue of human GLP-1, while both tirzepatide and retatrutide are engineered from a GIP backbone. All three are albumin-binding peptides that carry a fatty-diacid side chain, but the lysine position holding that linker differs across the set; in retatrutide it sits at lysine 17. These are related but distinct molecules, not interchangeable variants, and no published trial compares them head to head.
The trial programme is unusually deep for a compound at this stage, running from receptor pharmacology through registered phase 3 outcome studies. Each entry below is described strictly as what the study set out to measure, not what it found:
A registered phase 3 programme now extends this work, including cardiovascular and kidney outcomes (TRIUMPH-Outcomes, NCT06383390), liver outcomes (SYNERGY-Outcomes, NCT07165028) and glycaemic endpoints in type 2 diabetes (TRANSCEND-T2D-1, NCT06354660). These records describe trial design and the endpoints under study; they are listed here as research context, not as findings a reader should expect.
For laboratory work, the practical considerations are storage stability, reconstitution and verified purity, handled as one would any acylated research peptide. Lyophilised retatrutide is typically held cold and protected from light and moisture, with longer-term storage in a freezer and short working periods at refrigerator temperature; like other peptides it is sensitive to repeated freeze-thaw cycles. Reconstitution is a routine dissolution step using an appropriate laboratory solvent, after which the solution is kept cold and used within a defined working window for analysis. None of this constitutes a preparation method for any use in humans or animals; it is bench handling of a reagent. See the reconstitution guide for general laboratory handling.
A vial that says retatrutide and a vial that is retatrutide are not automatically the same thing, and at this molecular weight an identity error is easy to make and hard to catch by eye. That gap is what a certificate of analysis closes: every Kovalabs batch ships with one, so the mass and purity of the material in hand can be checked against the documented identifiers (formula C221H342N46O68, CAS 2381089-83-2) rather than taken on trust. Mechanistically distinct compounds in the same catalogue include cagrilintide, a long-acting amylin-receptor agonist, and tesamorelin, a growth-hormone-releasing-hormone analogue on a different axis.
Three things sit at very different levels of certainty. The chemistry is nailed down: a defined 39-residue sequence on a GIP backbone, formula C221H342N46O68, CAS 2381089-83-2, indexed in PubChem, with a cryo-EM study that actually resolved the molecule bound to all three receptors. The mechanism is one step softer - in-vitro potency assays and rodent models describe how the triple agonism behaves, but agonising a receptor in a mouse is a long way from a measured result in a person. The human record is the thinnest tier: the trials are described here only as study design, what each set out to measure and never what it found, and the largest outcome studies are still in progress. It is not a licensed medicine, and it has not been shown to produce defined outcomes in humans.
Retatrutide is supplied by Kovalabs for laboratory and in-vitro research only. It is not a medicine, not a supplement, and not for human or veterinary use, and nothing on this page describes a dose, a route, a schedule or an outcome. It is an investigational compound that has not been evaluated by the MHRA or any comparable regulator for safety or efficacy in humans or animals. Every batch is third-party tested with a certificate of analysis. See the full research disclaimer for terms.
No. Retatrutide (LY3437943) is an investigational compound. It has not been approved as a medicine by the MHRA or any comparable regulator, and Kovalabs supplies it strictly as a research reagent for laboratory use, not for human or veterinary use.
Published in-vitro and structural studies report that a single retatrutide molecule activates three receptors: the GIP, GLP-1 and glucagon receptors. A 2024 cryo-EM study (Li et al., Cell Discovery) resolved its binding at each of the three, which is the structural basis for the description.
By receptor count and lineage. Semaglutide is described in the literature as a GLP-1 receptor mono-agonist, tirzepatide as a dual GIP/GLP-1 agonist, and retatrutide as a triple GIP/GLP-1/glucagon agonist. No published head-to-head trial directly compares the three.
Its molecular formula is C221H342N46O68 with a molecular weight of about 4731 g/mol. PubChem indexes it under CID 171390338, with a sodium-salt record at CID 171934787, and chemistry suppliers list the free-form CAS number as 2381089-83-2.
As bench handling of a research reagent only. Lyophilised retatrutide is typically kept cold, protected from light and moisture, and frozen for longer-term storage, with care taken over freeze-thaw cycles. Reconstitution is a dissolution step in a suitable laboratory solvent. None of this is a preparation method for any use in humans or animals; see the reconstitution guide for general laboratory handling.