Retatrutide, developmental code LY3437943, is an investigational synthetic peptide described in the peer-reviewed literature as a single-molecule agonist of three incretin-family receptors: the glucagon-like peptide-1 receptor (GLP-1R), the glucose-dependent insulinotropic polypeptide receptor (GIPR) and the glucagon receptor (GCGR).
Published phase 2 clinical trials have evaluated Retatrutide for weight management in adults with obesity and for glycaemic control in type 2 diabetes. This monograph summarises the published identity, mechanism and research context of the peptide as reported in the primary literature.
Oxford Research Peptides supplies Retatrutide strictly as a reference standard for in-vitro laboratory research. Nothing on this page constitutes medical advice or endorses any therapeutic use.
Retatrutide is a 39-residue synthetic peptide with a fatty-acid modification designed to extend plasma half-life through albumin binding, an approach shared with several long-acting incretin analogues in the same pharmacological class.
At a glance
- Class
- Triple-agonist incretin peptide
- Developmental code
- LY3437943
- Targets
- GLP-1R · GIPR · GCGR
- Format
- Lyophilised powder
- Purity target
- ≥ 99% (HPLC)
- Storage
- −20 °C, desiccated
- LY3437943 — Eli Lilly developmental code.
- Retatrutide — non-proprietary name.
- Triple GLP-1/GIP/glucagon receptor agonist — descriptive class name used in the literature.
- Family: Incretin mimetics.
- Sub-class: Triple GLP-1R / GIPR / GCGR agonists.
- Structural type: Modified linear peptide with fatty-acid tail.
- Research area: Receptor pharmacology, metabolic signalling.
- MOLECULAR FORMULA
- C226H344N50O68
- MOLECULAR WEIGHT
- 4731.4 g/mol
- CAS NUMBER
- 2381089-83-2
- DEVELOPMENTAL CODE
- LY3437943
- RESIDUE COUNT
- 39 amino-acid residues
- MODIFICATION
- Fatty-acid conjugate (albumin binding)
Retatrutide's defining pharmacological feature is co-activation of three related class B G-protein-coupled receptors from a single molecule. Each of the three targets is a component of the incretin / glucagon axis and, when activated, engages Gαs-coupled adenylate cyclase and elevates intracellular cyclic AMP.
In published discovery pharmacology, the compound is characterised as producing balanced potency across GLP-1R, GIPR and GCGR relative to the endogenous ligands, with the peptide backbone engineered to preserve engagement of all three receptors rather than optimise a single target.
Reported pharmacology (published literature)
- Full-agonist activity reported at GLP-1R, GIPR and GCGR in cell-based cAMP assays.
- Fatty-acid modification supports albumin binding and extended plasma half-life.
- Weekly dosing schedule evaluated in reported phase 2 trials.
| Receptor | Reported activity | Receptor class |
|---|---|---|
| GLP-1R | Full agonist | Class B GPCR |
| GIPR | Full agonist | Class B GPCR |
| GCGR | Full agonist | Class B GPCR |
Published pharmacokinetic reports characterise Retatrutide as suitable for once-weekly administration in clinical study protocols, consistent with the extended half-life expected from an albumin-binding fatty-acid modification.
- Receptor selectivity: Reported as balanced across GLP-1R, GIPR and GCGR — distinct from single-agonist and dual-agonist analogues.
- Downstream signalling: Elevated intracellular cAMP consistent with Gαs-coupled class B GPCR activation.
- Half-life: Reported to support once-weekly subcutaneous dosing in phase 2 clinical protocols.
- Receptor-binding assays — GLP-1R, GIPR and GCGR displacement or functional cAMP assays.
- Reference standard — analytical HPLC and mass-spectrometry method development.
- Comparative pharmacology — side-by-side profiling against single- and dual-agonist peptides such as Semaglutide and Tirzepatide.
- Structure–activity studies — in-vitro characterisation of modified analogues within the incretin-mimetic class.
Retatrutide reference standards are supplied lyophilised. Standard laboratory practice for incretin-class peptides applies: aseptic handling, quantitative reconstitution, and single-use aliquoting to minimise freeze-thaw cycles.
Analytical characterisation
- Reversed-phase HPLC at 214 nm for purity reporting (target ≥ 99% area).
- Orthogonal identity confirmation by mass spectrometry.
- Karl Fischer or gravimetric water content on the lyophilised solid where a certificate of analysis requires it.
- Lyophilised solid: −20 °C, desiccated, protected from light.
- Reconstituted stock: 2–8 °C for short-term work; aliquot at −20 °C for longer storage.
- Freeze-thaw: Minimise cycles; single-use aliquots recommended.
- Container: Low-binding vials to reduce peptide loss on surfaces.
Reconstitute per the laboratory SOP. A general procedure is documented in the accompanying Laboratory Reconstitution Guide. The summary below applies to Retatrutide as an incretin-class peptide:
- Equilibrate the sealed vial to room temperature.
- Introduce diluent (bacteriostatic or sterile water) slowly against the vial wall.
- Swirl gently to dissolve — do not vortex.
- Allow complete dissolution before aliquoting.
- Label each aliquot with peptide, concentration, date and analyst.
Evidence summary
Research limitations
- The compound is investigational — no regulatory approval is in place for therapeutic use in the United Kingdom.
- Available literature is dominated by sponsor-led studies; independent replication is still developing.
- Long-term safety and efficacy data beyond published phase 2 durations are not yet available.
- No head-to-head trials against every existing incretin analogue have been published.
Retatrutide (LY3437943) is an investigational triple-agonist peptide engineered to act at three incretin-family receptors — GLP-1, GIP and glucagon. It is supplied by Oxford Research Peptides strictly as a reference standard for in-vitro laboratory research.
Published pharmacology characterises Retatrutide as an agonist at the GLP-1 receptor (GLP-1R), the GIP receptor (GIPR) and the glucagon receptor (GCGR), with reported balanced activity across the three targets.
The published molecular formula for Retatrutide (LY3437943) is C226H344N50O68 with a reported molecular weight of approximately 4731 g/mol.
Lyophilised Retatrutide should be stored at −20 °C, protected from light and moisture. After reconstitution in a suitable diluent, aliquots should be stored at 2–8 °C for short-term work or at −20 °C for longer periods, with freeze-thaw cycles minimised.
Cited sources for this monograph. Click any inline reference to jump to the entry below.
References6
- 1.
Coskun T, Urva S, Roell WC, et al.. LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept.. Cell Metabolism. 2022;34(9):1234-1247.
- 2.
Jastreboff AM, Kaplan LM, Frías JP, et al.. Triple-hormone-receptor agonist retatrutide for obesity — a phase 2 trial.. New England Journal of Medicine. 2023;389(6):514-526.
- 3.
Rosenstock J, Frias J, Jastreboff AM, et al.. Retatrutide, a GIP, GLP-1 and glucagon receptor agonist, for people with type 2 diabetes: a randomised, double-blind, placebo and active-controlled, parallel-group, phase 2 trial.. The Lancet. 2023;402(10401):529-544.
- 4.
Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP.. Gastroenterology. 2007;132(6):2131-2157.
- 5.
Drucker DJ. Mechanisms of action and therapeutic application of glucagon-like peptide-1.. Cell Metabolism. 2018;27(4):740-756.
- 6.
de Graaf C, Donnelly D, Wootten D, et al.. Glucagon-like peptide-1 and its class B G protein–coupled receptors: a long march to therapeutic successes.. Pharmacological Reviews. 2016;68(4):954-1013.
- What is Retatrutide?
Introductory reference on Retatrutide (LY3437943) — a triple-agonist investigational peptide referenced in incretin pharmacology literature.
- Retatrutide Mechanism of Action
Receptor-level explanation of Retatrutide's activity at GLP-1R, GIPR and GCGR as reported in the published preclinical and clinical literature.
- GLP-1 Receptor Explained
Overview of the GLP-1 receptor: a Class B G-protein-coupled receptor central to incretin pharmacology and to a growing family of research peptides.
- GIP Receptor Explained
Overview of the GIP receptor: a class B G-protein-coupled receptor engaged by dual and triple incretin-agonist research peptides.
- Glucagon Receptor Explained
Overview of the glucagon receptor (GCGR): classification, hepatic signalling and its role as the third receptor in triple-agonist research peptides.
- Triple Agonists Explained
Educational overview of triple GLP-1 / GIP / glucagon receptor agonists — pharmacological rationale, structural strategy and comparison to single- and dual-agonist analogues.
Publication information
- Published
- 2026-07-15
- Updated
- 2026-07-15
- Reviewed
- 2026-07-15
- Version
- 1.0
Revision history
- v1.02026-07-15· Editorial Team
Initial publication as part of the Retatrutide authority cluster (Release 4.0).
Editorial standards
Content is reviewed against our editorial process for scientific accuracy, sourcing, and clarity. Read our editorial standards.
Conflict of interest
Next scheduled review: 2027-07-15. Our research methodology describes how the review is conducted.