◆ Weightloss · Triple Agonist · GLP-1 / GIP / Glucagon
Retatrutide (LY3437943): Mechanism, Clinical Studies & Research Data
A verified research summary of LY3437943 — the investigational triple-agonist peptide targeting the GLP-1, GIP, and glucagon receptors, developed by Eli Lilly.
Silverback Research Team
Independent Literature Review
Compound Data
✓ Research Grade| Compound Name | Retatrutide (LY3437943) |
| CAS Number | 2381089-83-2 (free base) |
| Molecular Weight | 4731.33 g/mol (anhydrous free base) |
| Molecular Formula | C221H342N46O68 |
| Sequence Length | 39 amino acids (GIP-based backbone) |
| Receptor Targets | GIPR · GLP-1R · GCGR (balanced triple agonist) |
| Elimination Half-life | ~6 days (human terminal half-life) |
| Form (Silverback) | Lyophilised powder, 10mg/vial |
| Purity (Silverback) | ≥99% by HPLC |
| Storage | −20°C sealed · 2–8°C post-reconstitution (≤28 days) |
| Developer | Eli Lilly and Company |
| Regulatory Status | Investigational — not approved by FDA or TGA |
Research use only. All information is sourced from published literature for informational purposes. Silverback Peptides products are strictly for laboratory research. Not for human consumption, therapeutic use, or veterinary use.
Overview
Key Takeaways
- Retatrutide (LY3437943) is an investigational 39-amino-acid peptide and the first balanced triple agonist of the GIP, GLP-1 and glucagon receptors.
- It is developed by Eli Lilly and is not approved by the FDA or the Australian TGA — it remains investigational and is supplied for laboratory research only.
- Published Phase 2 data (Jastreboff et al., NEJM 2023) reported mean weight reductions up to −24.2% at 48 weeks in the highest dose group.
Retatrutide (development code LY3437943) is an experimental synthetic 39-amino-acid peptide engineered as a unimolecular triple hormone-receptor agonist. It is structurally derived from a GIP peptide backbone and modified with non-coded residues to optimise multi-receptor signalling.
The molecule incorporates a C20 fatty diacid moiety conjugated via a linker, which enables reversible binding to circulating serum albumin. This protects the peptide from rapid renal filtration and enzymatic cleavage, supporting a once-weekly dosing schedule in clinical research.
Retatrutide is strictly investigational. It is not approved by any regulator, including the US FDA or the Australian Therapeutic Goods Administration. Silverback Peptides supplies it for laboratory research use only. For batch documentation see our Certificates of Analysis.
Mechanism of Action
Retatrutide acts as a balanced triple agonist across three metabolic receptors. In vitro human receptor assays report an EC50 of approximately 0.0643 nM at the GIP receptor, 0.775 nM at the GLP-1 receptor, and 5.79 nM at the glucagon receptor (Coskun et al., 2022).
The activity across these three pathways produces complementary, research-observed metabolic effects:
- GLP-1 receptor agonism — modulates central appetite signalling and delays gastric emptying.
- GIP receptor agonism — enhances glucose-dependent insulin secretion and modulates adipose tissue function.
- Glucagon receptor agonism — increases energy expenditure and hepatic fatty-acid oxidation, a pathway absent in single GLP-1 agonists.
Key Published Studies
The Phase 2 double-blind, randomised, placebo-controlled obesity trial (Jastreboff et al., NEJM 2023) evaluated 338 adults over 48 weeks. The figures below are the least-squares mean body-weight changes. Note the distinction between the 24-week primary endpoint and the 48-week secondary endpoint — they are frequently conflated.
“At 48 weeks, weight reductions of at least 5%, 10% and 15% occurred in 100%, 93% and 83% of participants in the 12 mg group respectively.”
| Dose group | 24-week (primary) | 48-week (secondary) |
|---|---|---|
| 1 mg | −7.2% | −8.7% |
| 4 mg (combined) | −12.9% | −17.1% |
| 8 mg (combined) | −17.3% | −22.8% |
| 12 mg | −17.5% | −24.2% |
| Placebo | −1.6% | −2.1% |
Storage & Handling
Lyophilised retatrutide should be stored sealed at −20°C until required for research use. Once reconstituted with bacteriostatic water, the solution should be stored at 2–8°C and used within 28 days.
Avoid repeated freeze-thaw cycles, direct light exposure, and vigorous agitation during reconstitution.
References
- [1] Jastreboff AM, Kaplan LM, Frías JP, et al. Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial. N Engl J Med. 2023;389(6):514-526. DOI ↗
- [2] 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 Metab. 2022;34(9):1234-1247. DOI ↗