Retatrutide, also known as LY3437943, is a 39-amino-acid, lipidated peptide engineered as a single-molecule agonist of the GIP receptor (GIPR), GLP-1 receptor (GLP-1R), and glucagon receptor (GCGR). Its molecular design combines a GIP-derived peptide backbone with noncanonical amino acids, site-specific fatty-diacid conjugation, and C-terminal amidation to support multireceptor activity and prolonged pharmacokinetic behavior.
Retatrutide is currently an investigational peptide. As of August 2026, multiple pivotal Phase 3 studies have reported positive topline results, while regulatory submission has not yet been completed. Eli Lilly has stated that it plans to submit a U.S. Biologics License Application in Q1 2027.
Product Information
| Property | Specification |
|---|---|
| Product Name | Retatrutide |
| Development Code | LY3437943 |
| CAS No. | 2381089-83-2 |
| Peptide Length | 39 amino acids |
| Peptide Class | GIP/GLP-1/glucagon receptor triagonist |
| Primary Targets | GIPR, GLP-1R, GCGR |
| Lipid Modification | C20 fatty diacid conjugated through γ-Glu-AEEA at Lys17 |
| Noncanonical Residues | Aib at positions 2 and 20; α-Me-Leu at position 13 |
| C-Terminus | Amide |
| Form | Lyophilized peptide |
| Research Areas | Metabolic signaling, incretin biology, receptor pharmacology |
CAS 2381089-83-2 is registered for retatrutide/LY3437943 in the FDA Global Substance Registration System.
Retatrutide Sequence and Molecular Design
Sequence:
Y{Aib}QGTFTSDYSI{α-Me-Leu}LDK-Lys{diacid-C20-γ-Glu-(AEEA)}AQ{Aib}AFIEYLLEGGPSSGAPPPS-NH₂
Retatrutide is not simply a longer GLP-1 analog. Its pharmacology is created by combining several structural design elements within one 39-residue peptide.
Positions 2 and 20 contain α-aminoisobutyric acid (Aib), while position 13 contains α-methyl-leucine (α-Me-Leu). Published structural analyses of LY3437943 identify these non-natural residues as important components of the molecule's receptor activity and resistance to enzymatic degradation.
At Lys17, a C20 fatty diacid is attached through a γ-Glu/AEEA-containing linker. This lipidation strategy promotes reversible albumin association and contributes to the extended pharmacokinetic profile of the molecule. Retatrutide has a reported clinical half-life of approximately 6 days, supporting the once-weekly dosing schedule evaluated in clinical development.
Triple Receptor Agonism
Retatrutide was designed to activate three metabolically relevant G-protein-coupled receptors within one peptide:
| Receptor | Gene | Research Context |
|---|---|---|
| GIP receptor | GIPR | Incretin signaling and metabolic regulation |
| GLP-1 receptor | GLP1R | Glucose-dependent insulin signaling, appetite and metabolic research |
| Glucagon receptor | GCGR | Hepatic metabolism and energy-expenditure pathways |
Early pharmacological characterization showed activity at all three receptors, with relatively strong GIPR activity and more balanced GLP-1R/GCGR agonism. In preclinical models, glucagon-receptor engagement contributed an energy-expenditure component in addition to the effects associated with GIPR and GLP-1R signaling.
This multireceptor architecture is what distinguishes retatrutide from single GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists.
Why the Lipidated Lysine Matters
The Lys17 modification is part of the molecular identity of retatrutide, not simply an optional solubility tag.
A C20 fatty diacid connected through the γ-Glu/AEEA linker substantially increases hydrophobic character relative to the unmodified peptide backbone and enables albumin association. This contributes to prolonged systemic exposure while also making synthesis and purification more demanding.
For synthetic research material, We think this is one of the most important quality considerations. A 39-residue peptide with the correct backbone but an incorrect lipid attachment site is not chemically equivalent to retatrutide.
Researchers developing lipidated analogs, altered linker designs, or related incretin receptor agonists can use our Custom Peptide Synthesis capabilities for project-specific sequence and modification requirements.
Research Applications
Retatrutide is relevant to research involving GIPR, GLP-1R and GCGR signaling, multireceptor agonist pharmacology, metabolic pathway studies, incretin biology, peptide lipidation, albumin-binding strategies, and structure–activity relationships of long-acting peptide analogs.
Its architecture is also useful as a reference for scientists studying how noncanonical amino acids, receptor-biasing substitutions, linker chemistry, and fatty-acid conjugation can be combined within a single peptide scaffold.
Current Clinical Research Context
Retatrutide remains investigational, but its clinical program has generated substantial scientific interest.
In the published Phase 2 obesity trial, the highest evaluated dose produced a mean body-weight reduction of 24.2% at 48 weeks, compared with 2.1% with placebo. Retatrutide continued to show a dose-dependent response through the trial period.
In May 2026, Lilly reported topline results from the Phase 3 TRIUMPH-1 study. Participants receiving 12 mg had an average 28.3% weight reduction at 80 weeks, while 45.3% achieved at least 30% weight reduction.
Additional Phase 3 data reported in July 2026 included average weight reductions of up to 20.8% in adults with type 2 diabetes and obesity or overweight in TRIUMPH-2 and 22.6% in participants with severe obesity and established cardiovascular disease in TRIUMPH-3.
These clinical findings provide biological context for receptor research involving retatrutide but do not constitute specifications for research-grade synthetic material.
Quality Considerations for Synthetic Retatrutide
Retatrutide presents a different analytical challenge from a conventional linear peptide.
The final product should be evaluated not only for chromatographic purity but also for molecular identity, incorporation of the noncanonical residues, the intended C-terminal amide, and the site-specific Lys17 lipid modification.
For a lipidated 39-mer, purification behavior can also differ substantially from the corresponding non-lipidated precursor because the C20 diacid changes overall hydrophobicity.
We therefore consider sequence identity, modification identity, molecular mass, and HPLC purity together when evaluating material for receptor or biochemical research.
More information on analytical HPLC, mass spectrometry, and batch documentation is available through our Peptide Quality Control resource.
Purity and Experimental Planning
The appropriate purity specification should reflect the intended experiment.
Preliminary analytical or method-development work may not require the same specification as quantitative receptor assays, cell-based experiments, or other sensitive biological workflows. Researchers should also consider counterion content and, where relevant, endotoxin requirements rather than relying only on the HPLC percentage.
Our Recommended Peptide Purity guide provides application-oriented considerations for selecting an appropriate specification.
For this type of highly modified peptide, We think correct molecular form is more important than pursuing a nominal purity number while overlooking lipidation or sequence identity.
Frequently Asked Questions
What receptors does retatrutide activate?
Retatrutide is a single peptide agonist of GIPR, GLP-1R and GCGR. This triple-receptor profile distinguishes it from GLP-1-only and dual GIP/GLP-1 receptor agonists.
Is retatrutide a “GLP-3”?
No. “GLP-3” is not a scientifically recognized receptor or peptide class. Retatrutide is more accurately described as a GIP/GLP-1/glucagon receptor triple agonist. Lilly has specifically noted that the informal “GLP-3” label is scientifically inaccurate.
How many amino acids are in retatrutide?
Retatrutide contains 39 amino-acid residues, including Aib substitutions at positions 2 and 20 and α-Me-Leu at position 13. A C20 fatty diacid is conjugated at Lys17.
Why is retatrutide lipidated?
The fatty-diacid modification promotes albumin association and contributes to extended systemic exposure. The reported clinical half-life is approximately 6 days.
Is retatrutide FDA approved?
No. As of August 2026, retatrutide remains investigational. Lilly has reported positive Phase 3 results and currently plans a U.S. regulatory submission in Q1 2027.
Research Use Only
Retatrutide is supplied for research use only. It is not intended for therapeutic, or human use.