Retatrutide (CP-Reta): Research Guide to the GIP/GLP-1/Glucagon Triple Agonist

Last reviewed: October 2026 · Cleared Peptides research team

Research use only. Retatrutide (CP-Reta): Research Guide to the GIP/GLP-1/Glucagon Triple Agonist is supplied for laboratory research. It is not a drug, food, cosmetic, or dietary supplement. It is not FDA-approved. It is not for human or veterinary administration. This page does not give a dose or a method of administration. A study cited on this page describes that study’s own test article. It does not make this lot an approved medicine. To check a fact, open the PubMed or DOI link, confirm the authors and year, and match the paper’s compound name, CAS number, or sequence to the specification table. The full method is on the research desk page. Identity and purity for a lot are only what that lot’s certificate of analysis reports. An HPLC percentage is not a sterility result and not an endotoxin result unless the certificate prints those tests.

Retatrutide (development code LY3437943) is a synthetic, lipidated peptide that has become one of the most closely followed compounds in incretin-receptor research. It is notable because a single molecule is characterized as an agonist at three related G-protein-coupled receptors: the GIP receptor, the GLP-1 receptor and the glucagon receptor. This guide summarizes what the published laboratory literature reports about its structure, receptor pharmacology and analytical characterization.

In this guide:

• What is retatrutide?
• Chemical structure and identifiers
• Receptor pharmacology
• How it compares with tirzepatide and semaglutide
• Purity and analytical testing
• Storage and handling
• Analytical testing
• FAQ

Other names

The heading on this page stays the published compound name, because that is the name researchers search. The catalog code is the label Cleared Peptides prints on that research material. It is the same substance, not a second compound, and it is not a CAS name.

What Is Retatrutide?

Retatrutide belongs to the family of unimolecular multi-receptor agonists — peptides engineered so that one sequence engages more than one receptor of the glucagon/secretin receptor family. Earlier generations of research compounds acted at one receptor (for example semaglutide at GLP-1R) or two receptors (for example tirzepatide at GIPR and GLP-1R). Retatrutide adds glucagon-receptor (GCGR) activity, which is why it is commonly described as a “triple agonist” or “GGG tri-agonist”.

For laboratories, retatrutide is used as a reference ligand when comparing receptor selectivity, signaling bias and ligand-binding behavior across the three receptors, and when benchmarking it against single and dual agonists.

Retatrutide Chemical Structure and Identifiers

Two structural features are frequently discussed in the literature. First, the non-coded amino acids (Aib and α-methylated residues) reduce susceptibility to dipeptidyl peptidase-4 (DPP-4) and other proteases, a common design strategy for incretin-receptor peptides. Second, the fatty diacid side chain promotes reversible binding to serum albumin, which is the basis of extended-half-life peptide design and a frequent subject of ligand-binding studies.

Retatrutide Receptor Pharmacology (In-Vitro)

In published cell-based assays using recombinant human receptors, retatrutide stimulates cAMP accumulation at GIPR, GLP-1R and GCGR. Reported potency is highest at the GIP receptor, with lower relative potency at the GLP-1 and glucagon receptors — so the molecule is not “balanced” across the three targets. This imbalance is itself of research interest, because it allows investigators to explore how the relative contribution of each receptor shapes downstream signaling.

Typical laboratory applications include:

• Receptor-selectivity and potency (EC₅₀) comparisons against GLP-1R-selective and dual GIPR/GLP-1R agonists
• cAMP, β-arrestin recruitment and receptor-internalization assays
• Albumin-binding and serum-shift studies of lipidated peptides
• Analytical method development (HPLC, LC-MS) for long acylated peptides

Retatrutide vs Tirzepatide vs Semaglutide

For a deeper side-by-side, see our retatrutide vs tirzepatide vs semaglutide comparison.

Retatrutide Purity and Analytical Testing

Because retatrutide is a long, lipidated peptide, impurities from synthesis (deletion sequences, incomplete acylation, oxidation products) can be difficult to resolve. Reliable research material should be supported by: reverse-phase HPLC purity data, mass-spectrometry identity confirmation matching the expected molecular weight, and a lot-specific Certificate of Analysis. Every lot of Cleared Peptides retatrutide (CP-Reta) is tested by an independent laboratory and its COA is published on our COA page before sale.

Storage and Laboratory Handling

Lyophilized retatrutide is typically stored at −20 °C, sealed, dry and protected from light. Allow vials to reach room temperature before opening to limit condensation, minimize freeze–thaw cycles, and handle according to institutional chemical-hygiene procedures. For reconstitution in laboratory assays, researchers commonly use sterile water or buffer selected for the assay; see our reconstitution water.

Analytical testing notes for Retatrutide

Retatrutide is identified in this guide as CAS 2381089-83-2, formula C221H342N46O68, listed mass ≈4731.3 g/mol. An identity test compares a measurement with those values. A mass spectrum is the usual measurement for a peptide. FTIR, when a certificate uses it, is a supporting infrared fingerprint and is less specific for closely related sequences.

Retatrutide carries a fatty-acid or other lipophilic modification, so it is among the later-eluting peptides on a C18 column. Laboratories often raise the acetonitrile fraction, the column temperature, or move to a C8 or C4 column so the main peak is sharp enough to integrate. The mass used for identity has to include the lipid chain and linker, not only the amino-acid backbone. Area-percent purity still ignores water and counterion.

HPLC purity for this material is an area-percent result at the wavelength and gradient the laboratory states, commonly ultraviolet detection near 214 nm on a reversed-phase column. The instrument is a gradient pump, injector, column oven, and UV or diode-array detector. That percentage is not the number of milligrams in the vial. Water, acetate, trifluoroacetate, and other UV-silent material can dominate the gross weight while the purity figure stays high. Net peptide content, from an assay or amino-acid analysis, is the separate result to read when the certificate reports it.

A sterility test and an endotoxin test are not included in a chemical purity result. The compendial sterility test is a culture method (USP <71>): membrane filtration or direct inoculation into fluid thioglycollate medium and soybean-casein digest medium, incubated for 14 days. A PCR sterility screen uses a thermal cycler to detect microbial DNA and is a different method. The endotoxin test (USP <85> LAL, or USP <86> recombinant Factor C) reports endotoxin units with an incubating reader or a cartridge reader. Use a result only when that method is printed on the lot certificate. One published example in this catalog states that the report does not cover microbial contamination or endotoxins. The full description of equipment, standards, and how US laboratory accreditation works is in peptide analytical testing. Lot records are on the COA page.

Frequently Asked Questions

What does GLP-3 mean?

GLP-3 is an informal name. The published description is a peptide studied at the GIP, GLP-1, and glucagon receptors. The registry name on this page is retatrutide, CAS 2381089-83-2. The catalog code is CP-Reta.

Is CP-R a different peptide from CP-Reta?

No. CP-R is the short form of the catalog code CP-Reta printed on the retatrutide research material.

What is retatrutide?

Retatrutide (LY3437943) is a synthetic 39-amino-acid lipidated peptide characterized in published in-vitro studies as an agonist at the GIP, GLP-1 and glucagon receptors.

What is the CAS number of retatrutide?

The CAS registry number of retatrutide is 2381089-83-2; its molecular formula is C221H342N46O68 (MW ≈4731.3 g/mol).

Why is retatrutide called a triple agonist?

Because one molecule activates three receptors — GIPR, GLP-1R and GCGR — in cell-based assays, unlike single (GLP-1R) or dual (GIPR/GLP-1R) agonists.

Is CP-Reta the same compound as retatrutide?

Yes. CP-Reta is Cleared Peptides’ product code for research-grade retatrutide; identity is confirmed by mass spectrometry on each lot COA.

Can retatrutide from Cleared Peptides be used in people?

No. It is supplied strictly for laboratory research use only and is not for human or veterinary use.

Written by the Cleared Peptides Research Desk, the editorial desk of Cleared Wellness Group LLC. This is not a personal profile of a physician or a scientist, and it is not a fictional author. The checking method is public on the research desk page. Last reviewed October 2026.

Retatrutide research note: three receptors, four kinds of paper

Research use only. The material on this page is lyophilized retatrutide for laboratory research, catalog code CP-Reta, development code LY3437943, CAS 2381089-83-2. It is not a drug product. The clinical papers below studied a sponsor’s article under a protocol. They are not instructions, and this note does not repeat their dose arms.

What the molecule is, in the catalog and in the papers

The specification table lists a 39-residue peptide, formula C221H342N46O68, mass about 4731.3 g/mol, with Aib and α-methyl-L-leucine in the backbone and a C20 fatty diacid on Lys17 through a γ-glutamic acid and oligo-ethylene-glycol linker. That lipidation is why an identity test has to use the intact mass, including the lipid and the linker, not the bare peptide backbone. It is also why the peak is late on a C18 column. Those analytical points are expanded in the testing note already on the Learn guide.

Coskun, Urva, Roell, and colleagues introduced LY3437943 in Cell Metabolism in 2022 as one peptide with agonist activity at the glucagon receptor (GCGR), the GIP receptor (GIPR), and the GLP-1 receptor (GLP-1R). Their in-vitro description is specific: balanced activity at GCGR and GLP-1R, and more activity at GIPR. The same paper reports mouse work and a phase 1 single-ascending-dose study of that development article. PubMed 35985340, DOI 10.1016/j.cmet.2022.07.013.

An earlier short line on this page said potency was in the sub-nanomolar to low-nanomolar range. This note does not repeat that range. The sentence a reader can check is Coskun’s: more GIPR activity than the balanced GCGR and GLP-1R activity. The EC50 table is in the paper. A rounded phrase on a product page is not a substitute for it.

Do not collapse the later papers into one “result”

Urva, Coskun, Loh, and colleagues published a 12-week phase 1b multiple-ascending-dose trial in adults with type 2 diabetes (Lancet, 2022). That paper’s question was safety, pharmacokinetics, and pharmacodynamics of weekly LY3437943 in that protocol, with placebo and dulaglutide arms. PubMed 36354040, DOI 10.1016/S0140-6736(22)02033-5.

Rosenstock, Frias, Jastreboff, and colleagues published a phase 2 trial in adults with type 2 diabetes (Lancet, 2023), placebo-controlled and active-controlled. PubMed 37385280, DOI 10.1016/S0140-6736(23)01053-X.

Jastreboff, Kaplan, Frias, and colleagues published a separate phase 2 trial in adults with obesity (New England Journal of Medicine, 2023). PubMed 37366315, DOI 10.1056/NEJMoa2301972.

These are four different designs: discovery pharmacology plus a first-in-human dose study, a 12-week diabetes pharmacology study, a phase 2 diabetes study, and a phase 2 obesity study. Quoting a body-weight percentage from one of them as if it were a property of a research vial mixes a trial endpoint with a chemical specification. The percentage belongs to the randomized population and the article Lilly supplied for that trial.

Li and colleagues later published a structural study of how retatrutide engages GLP-1R, GIPR, and GCGR (Cell Discovery, 2024). Use that paper for binding poses, not for a clinical endpoint. PubMed 39019866, DOI 10.1038/s41421-024-00700-0.

How this differs from tirzepatide and semaglutide

Semaglutide, in Lau’s discovery paper, is a GLP-1 receptor analogue. Tirzepatide, in Willard’s pharmacology paper, is an imbalanced dual agonist at GIPR and GLP-1R, with bias at GLP-1R. Retatrutide adds GCGR activity and, in Coskun’s in-vitro description, puts relatively more activity on GIPR. “Triple” means three receptors in the assay, not three times the effect of a GLP-1 analogue. The side-by-side is on the comparison guide. Cagrilintide is not part of this set. It is an amylin analogue. Nisotirostide is not part of it either. Briere and colleagues describe nisotirostide as an NPY2 receptor agonist.

How to verify this note

1. Open Coskun 2022 and confirm the in-vitro line: more GIPR activity, balanced GCGR and GLP-1R activity, code LY3437943.
2. Match CAS 2381089-83-2, formula C221H342N46O68, and the C20 diacid on Lys17 to this page’s table. If a chromatogram’s mass lacks the lipid, it is not this specification.
3. Keep Urva 2022, Rosenstock 2023, and Jastreboff 2023 as separate trials. Do not add their endpoints together.
4. Read Li 2024 as structure. Read the certificate of analysis as the lot record. HPLC area percent is not sterility or endotoxin unless those lines are on the certificate.

Selected References

Laboratory note: solubility depends on salt form and solvent. This guide does not state a single solubility figure. Handling of lyophilized material is described in the peptide storage guide.

Research Use Only Notice

This guide is provided for educational and laboratory reference purposes. It summarizes published, primarily in-vitro and structural research literature and does not describe, recommend or imply any use in humans or animals. Products sold by Cleared Peptides are for laboratory research use only; they are not drugs, foods, cosmetics or dietary supplements, are not FDA-approved, and are not intended to diagnose, treat, cure, mitigate or prevent any disease. No dosing, administration or therapeutic information is provided.