Retatrutide, tirzepatide and semaglutide: receptor targets

Semaglutide, tirzepatide and retatrutide are three peptides from the same design lineage, distinguished by how many receptors they engage: one, two and three respectively. For a researcher reading the literature or characterising material, the differences that matter are structural and pharmacological, and the naming is a frequent source of confusion. This note compares them factually. Only retatrutide, listed by Alphex as GLP-3 (RT), is in our catalogue, and it is supplied as a laboratory reagent. All Alphex products are for laboratory and in-vitro research only.

The shared design

All three are synthetic peptides built on backbones from the glucagon superfamily (GLP-1, GIP, glucagon), modified in three consistent ways: substitution of protease-labile residues with non-natural ones such as alpha-aminoisobutyric acid (Aib) to resist enzymatic cleavage; attachment of a fatty acid or fatty diacid through a linker to a lysine side chain, promoting reversible albumin binding; and sequence engineering to tune receptor affinity. The lipidation is why all three are markedly less water-soluble and more prone to aggregation and plastic adsorption than short research peptides.

Receptor targets

• Semaglutide: GLP-1 receptor. A single-receptor ligand on a GLP-1 backbone, with Aib at position 8 and a C18 diacid.
• Tirzepatide: GIP and GLP-1 receptors. Built on a GIP-like backbone with a C20 diacid, engaging both receptors with differing relative potency.
• Retatrutide (LY3437943, listed as GLP-3 (RT)): GIP, GLP-1 and glucagon receptors. 39 residues, C20 diacid, CAS 2381089-83-2, 4731.3 g/mol. See the GLP-3 (RT) guide.

The receptor pharmacology of each is documented in published in-vitro work from the respective development programmes, which is the appropriate primary source for relative potencies.

Naming, and why it confuses

Each compound has a development code (LY3437943 for retatrutide), an INN (retatrutide), brand names for the authorised products where they exist, and various research-market names. "Triple agonist", "dual agonist" and "GLP-3" are informal descriptors rather than formal nomenclature; Alphex uses "GLP-3 (RT)" as a catalogue name and states the INN, code and CAS on the specification so there is no ambiguity about what is being supplied. Research-grade material is not the pharmaceutical product, is not a medicine, and is supplied for laboratory use only.

Analytical and handling differences

• Size: 31 to 39 residues; all are large by research peptide standards, and all show a multiply-charged envelope in electrospray rather than a single ion. See mass spectrometry explained.
• Purity: reaching 99+% is genuinely difficult at this length with lipidation, and a certificate showing no minor peaks at all should raise questions rather than confidence. See 98% versus 99+%.
• Solubility: all three need slow, gentle reconstitution, preferably into a mildly alkaline buffer; cloudiness means aggregation. See the solubility guide.
• Adsorption: the diacid binds plastic as readily as albumin; low-binding tubes for dilute solutions. See adsorption.
• Molar comparison: masses differ by hundreds of daltons, so mass-based comparisons between them are meaningless without conversion.

What Alphex supplies

GLP-3 (RT) only, in 5, 10, 20 and 30 mg vials, at 99+% HPLC purity (220 nm, reference standard), batch-numbered, UK stock, certificate available before purchase. We do not stock semaglutide or tirzepatide. See why the catalogue is small.

Alphex research peptides are supplied for laboratory and in-vitro research by qualified researchers only. They are not authorised for human or veterinary use, and nothing here describes or recommends any such use.

Research use only. Alphex products are supplied exclusively for laboratory and in-vitro research by qualified researchers. They are not authorised for human or veterinary use, and nothing in this note is advice on any such use.

Published 28 July 2026. Alphex reviews research notes when the testing method, the catalogue or UK guidance changes.

Alphex Research Team

Alphex Limited, UK research peptide supplier

The Alphex research team writes and maintains these notes for UK laboratories buying research peptides. Every batch Alphex lists is verified by reverse-phase HPLC with a batch-matched Certificate of Analysis. Content covers laboratory and in-vitro research only.