Retatrutide is a synthetic 39-residue acylated peptide that activates three receptors at once — GIP, GLP-1 and glucagon — making it the most-studied triple agonist in metabolic research. Its distinguishing feature is the glucagon receptor arm, which adds a direct energy-expenditure and hepatic-substrate component absent from single and dual incretin agonists. We supply research-grade retatrutide as lyophilized powder in sealed vials, for laboratory investigation only.
Retatrutide is not an approved medicine anywhere as of 2026. It is an investigational molecule with published clinical trial data behind it, and research-grade material is a reference chemical, not a therapeutic product.
What is retatrutide, precisely
Retatrutide, also cited as LY3437943 in the literature, is a proglucagon-superfamily peptide engineered so that a single sequence retains meaningful affinity at three related class B G-protein-coupled receptors. GIP, GLP-1 and glucagon all derive from ancestral genes with substantial sequence homology, which is why one backbone can be tuned to hit all three — the receptors are close enough cousins that overlapping pharmacophores exist. Building a triple agonist is therefore less about bolting three drugs together and more about finding substitutions that keep three affinity profiles in a usable ratio simultaneously.
Origin and structure
- Backbone. A 39-residue GIP-related sequence in the proglucagon superfamily, comparable in length to tirzepatide but with substitutions that restore glucagon receptor affinity.
- Alpha-aminoisobutyric acid substitutions. Aib near the N-terminus removes the DPP-4 cleavage site and rigidifies the helical region that docks into the receptor extracellular domain.
- C20 fatty diacid acylation. Attached through a gamma-glutamyl and ethoxy spacer, driving reversible albumin binding and the extended circulating persistence reported in pharmacokinetic work.
- Reported receptor balance. Published characterisation describes potent GIP receptor activity, strong GLP-1 receptor activity, and comparatively weaker but pharmacologically relevant glucagon receptor activity. The molecule is deliberately unbalanced.
Catalog identifiers: CAS 2381089-83-2, molecular formula C221H342N46O68, molecular weight 4731.30 Da. That mass sits close to tirzepatide, so a mass spectrometry identity check distinguishing the two needs adequate resolution and a theoretical mass to compare against rather than a visual judgement.
How retatrutide is thought to work
The GIP and GLP-1 arms behave as they do in other incretin agonists: Gs coupling, cAMP accumulation, and glucose-dependent amplification of insulin secretion in islet preparations, with central and vagal receptor populations implicated in the feeding-behaviour changes reported in rodents. The glucagon arm is what makes retatrutide mechanistically distinct.
Glucagon receptor agonism in hepatocytes has been reported to raise cAMP, promote hepatic lipid oxidation and increase energy expenditure in preclinical models. In isolation that would also raise hepatic glucose output, which is metabolically unhelpful — the design logic of a triple agonist is that concurrent incretin-driven, glucose-dependent insulin secretion offsets the glycaemic consequence of glucagon receptor activation while its energy-expenditure component is retained. Whether that offset holds across the full concentration range is exactly the kind of question researchers use this molecule to interrogate, and it cannot be answered without arms that separate the three receptor contributions.
The trade-off inherent in the design is worth stating plainly. Every additional receptor added to a single ligand narrows the chemical space in which all affinities remain acceptable, so triple agonists are typically weaker at each individual receptor than a dedicated agonist for that receptor would be. Retatrutide is not a more potent GLP-1 agonist than semaglutide, and it is not a more potent GIP agonist than a selective GIP analog. What it offers experimentally is simultaneity — three signals arriving on the same tissue at the same time in a fixed ratio, which no combination of separate compounds can reproduce exactly because their pharmacokinetics diverge.
What research has examined
- Receptor and cell studies. cAMP potency at human GIPR, GLP-1R and GCGR expressed in recombinant lines, binding assays, and beta-arrestin recruitment work used to establish the three-way activity ratio that defines the molecule.
- Rodent studies. Diet-induced obesity models reporting changes in food intake and adiposity, indirect calorimetry work examining energy expenditure attributable to the glucagon arm, and hepatic lipid content studies. Receptor-knockout and selective-antagonist designs are used to attribute observed effects to individual arms.
- Human clinical trials. Phase 2 results have been published, and phase 3 programmes in obesity and related metabolic endpoints have reported data as of 2026 — summarised in our note on what the published retatrutide data actually showed. These describe an investigational pharmaceutical under clinical supervision and do not transfer to research-grade powder.
Hepatic endpoints attract particular attention because the glucagon arm acts directly on liver, making retatrutide a useful probe for studies of hepatic lipid handling where an incretin-only agonist would act indirectly.
Two practical cautions apply when reading the retatrutide literature. First, the receptor activity ratio reported for the molecule is assay-dependent: cAMP potency measured in a recombinant overexpression system does not necessarily reproduce the ratio seen in a primary cell with native receptor density, so ratios quoted from different papers are not directly comparable. Second, glucagon receptor pharmacology diverges more across species than incretin receptor pharmacology, so a rodent result driven by the glucagon arm should be read as a species-specific observation until confirmed at the human receptor. Designs that include a glucagon receptor antagonist arm are the cleanest way to test whether that arm is carrying an observed effect.
Forms and sizes we supply
| Attribute | Specification |
|---|---|
| Form | Lyophilized powder, sealed glass vial |
| Sizes | 10 mg, 20 mg, 30 mg, 48 mg, 60 mg |
| Purity | Greater than or equal to 99% by HPLC, lot-matched COA |
| CAS | 2381089-83-2 |
| Molecular weight | 4731.30 Da |
| Formula | C221H342N46O68 |
| Class | Acylated triple GIP / GLP-1 / glucagon receptor agonist |
| Also cited as | LY3437943 |
| Intended use | Laboratory research only |
Sizes and current pricing sit on the retatrutide product page, alongside the rest of the GLP-1 and incretin range.
Reconstitution and storage in a lab context
The calculation is arithmetic, not instruction: a 20 mg vial reconstituted with 2 mL of bacteriostatic water yields 10 mg/mL, equal to 10,000 mcg/mL, so 0.1 mL of that solution carries 1,000 mcg of peptide. Direct the diluent down the vial wall, let the cake dissolve without shaking, and confirm a clear solution before proceeding. Acylated peptides of this size aggregate readily under mechanical stress, and aggregation is invisible in a purity certificate issued before you touched the vial.
Sealed lyophilized material keeps at minus 20 degrees Celsius, protected from light and moisture. Reconstituted solution is held at 2 to 8 degrees Celsius and used within the study window. Aliquot at the point of reconstitution so that repeated freeze-thaw rounds do not erode a single expensive stock. Full mechanics are in our reconstitution guide.
Purity, COA and how to read it
A retatrutide certificate should carry an HPLC chromatogram with main-peak area percentage, a mass spectrometry identity result compared against the theoretical 4731.30 Da, net peptide content, lot number and analysis date. Because retatrutide and tirzepatide are close in mass and both are C20-acylated 39-residue peptides, identity confirmation matters more here than for structurally distinctive molecules — a purity figure alone does not tell you which peptide is in the vial. Read the mass spectrometry identity note, and always match the lot to your vial label.
One more selection point separates retatrutide from the rest of the incretin range in practice. Because three arms operate at once, the concentration-response curve for any composite readout is unlikely to be a simple sigmoid: different receptor contributions dominate at different occupancies, and a curve fitted as though one mechanism were operating will produce a potency value that describes nothing in particular. Wide concentration ranges with dense sampling, rather than the three or four points typical of a single-receptor experiment, are what make retatrutide data interpretable, and that has direct consequences for how much material a study consumes.
Regulatory status
Retatrutide has no marketing approval in any jurisdiction as of 2026. It is investigational: studied in registered clinical trials under regulatory oversight, not available as a prescribed medicine. Research-grade retatrutide is sold as a reference chemical, research use only, not for human or veterinary administration. The existence of positive trial data does not create any human-use pathway for laboratory material — see research use only, explained.
Related peptides and comparisons
The natural comparators are the dual agonist tirzepatide and the mono-agonist semaglutide, covered in retatrutide vs tirzepatide and semaglutide vs retatrutide. Other glucagon-receptor-containing peptides worth placing beside it are survodutide.