Retatrutide — Research Peptide Overview, Specifications, and Sourcing

At-a-Glance Specifications

CAS Number

2381089-83-2

Molecular Weight

~4703.4 g/mol

Molecular Formula

C₂₂₁H₃₃₉N₄₇O₆₇

Amino Acid Sequence

39-amino-acid modified GIP/GLP-1/glucagon triple agonist (LY3437943): His-Aib-Glu-Gly-Thr-Phe-Thr-Ser-Asp-Val-Ser-Ser-Tyr-Leu-Glu-Glu-Glu-Glu-Ala-Lys(C20 fatty diacid)-Glu-Phe-Ile-Glu-Trp-Leu-Leu-Ala-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Ser-NH2

Purity

≥99% (HPLC verified)

Physical Form

Lyophilized powder

Storage

-20°C lyophilized; 2-8°C reconstituted

Synonyms

LY3437943, Eli Lilly triple agonist

What Is Retatrutide?

Retatrutide (LY3437943) is a novel triple-hormone receptor agonist that simultaneously activates the glucose-dependent insulinotropic polypeptide (GIP) receptor, the glucagon-like peptide-1 (GLP-1) receptor, and the glucagon receptor. Developed by Eli Lilly and Company, retatrutide represents the most advanced iteration of the multi-receptor agonist approach to metabolic research, building upon the dual-agonist paradigm established by tirzepatide.

Structurally, retatrutide is a 39-amino-acid synthetic peptide incorporating a C20 fatty diacid moiety that enables albumin binding and extends its circulating half-life to approximately 6 days, supporting once-weekly dosing in research protocols. The peptide sequence has been engineered to provide balanced agonism across all three target receptors, with particular emphasis on retaining meaningful glucagon receptor activation alongside GIP and GLP-1 receptor engagement.

The addition of glucagon receptor agonism distinguishes retatrutide from its predecessors. Glucagon signaling promotes hepatic lipid oxidation, increases energy expenditure, and reduces hepatic steatosis through mechanisms that complement the appetite-suppressive and insulin-sensitizing effects of GIP and GLP-1 receptor activation. This three-pronged approach has produced remarkable results in early clinical research, with the phase 2 trial reporting mean body weight reductions of up to 24.2% at 48 weeks, establishing retatrutide as potentially the most effective single agent for weight reduction studied to date.

For wholesale research suppliers, retatrutide represents the cutting edge of incretin research compounds. Demand is rapidly increasing as academic institutions and pharmaceutical companies seek to understand the pharmacology of triple-receptor agonism and develop next-generation metabolic research strategies.

Mechanism of Action

Retatrutide’s mechanism encompasses three distinct but synergistic receptor-mediated pathways, creating a comprehensive metabolic signaling profile.

GIP Receptor Agonism

Retatrutide activates the GIP receptor with high potency, stimulating glucose-dependent insulin secretion and modulating adipose tissue metabolism. GIPR activation contributes to improved lipid handling and may enhance energy expenditure through direct effects on adipocytes. The GIPR component works synergistically with GLP-1R activation to produce effects on glycemic control that exceed single-receptor agonism.

GLP-1 Receptor Agonism

GLP-1 receptor engagement drives appetite suppression through central and peripheral mechanisms, delays gastric emptying, and enhances glucose-dependent insulin secretion. The GLP-1R component of retatrutide provides the well-established appetite-regulatory effects that underlie the weight loss observed with GLP-1-based research compounds.

Glucagon Receptor Agonism

The inclusion of glucagon receptor (GCGR) agonism distinguishes retatrutide from all previous incretin-based compounds. Glucagon receptor activation promotes hepatic glycogenolysis and gluconeogenesis, but more importantly for metabolic research, it enhances hepatic fatty acid oxidation, increases thermogenesis and energy expenditure, and reduces hepatic lipid content. Coskun et al. (2022) demonstrated that the glucagon component of retatrutide contributed significantly to weight loss and metabolic improvement beyond what GIP/GLP-1 dual agonism alone could achieve (PMID: 35320649).

Synergistic Triple-Agonist Pharmacology

The three receptor activations produce complementary metabolic effects: GLP-1R drives appetite reduction and glycemic control; GIPR enhances insulin sensitivity and lipid metabolism; GCGR increases energy expenditure and hepatic fat oxidation. This tripartite mechanism addresses multiple components of metabolic dysfunction simultaneously. Jastreboff et al. (2023) reported the phase 2 trial results demonstrating the unprecedented efficacy of this triple-agonist approach (PMID: 37351564).

Hepatic Mechanisms

Retatrutide’s glucagon component drives direct hepatic effects including enhanced fatty acid beta-oxidation, increased mitochondrial activity in hepatocytes, and reduced de novo lipogenesis. These hepatic mechanisms are particularly relevant to NASH/NAFLD research and represent a key differentiator from dual-agonist compounds.

Research Applications

Obesity Research

Retatrutide has established new efficacy benchmarks in obesity research, with phase 2 data showing mean weight reductions exceeding 24% at the highest dose. These unprecedented results have made retatrutide the reference compound for next-generation obesity research.

Metabolic Syndrome Research

The triple-agonist mechanism addresses multiple metabolic syndrome components simultaneously, including obesity, insulin resistance, dyslipidemia, and hepatic steatosis, making retatrutide a valuable tool for studying integrated metabolic improvement strategies.

NASH/NAFLD Research

Retatrutide’s glucagon receptor component drives direct hepatic fat reduction through enhanced fatty acid oxidation, positioning it as a leading research compound for non-alcoholic fatty liver disease studies. Early clinical data showed significant reductions in hepatic fat content.

Triple-Agonist Pharmacology Research

As the first triple GIP/GLP-1/glucagon agonist in clinical development, retatrutide is a key tool for understanding the pharmacology of multi-receptor agonism. Researchers use it to dissect the relative contributions of each receptor to metabolic outcomes.

Comparative Incretin Research

Retatrutide serves as the triple-agonist benchmark in comparative studies alongside semaglutide (single), tirzepatide (dual), and other emerging multi-agonists, enabling systematic investigation of receptor-number-dependent efficacy.

Available Formats and Bulk Options

• Standard Research Vials: 3 mg and 5 mg lyophilized powder per vial
• High-Volume Vials: 10 mg per vial
• Bulk Lyophilized Powder: Available in 50 mg, 100 mg, and 500 mg quantities
• Custom Formulations: Available for qualified institutional accounts

Wholesale Pricing Summary

For detailed pricing, visit our wholesale pricing page or contact our B2B team.

Quality, Testing, and Certificates of Analysis

• HPLC Purity: RP-HPLC confirms ≥99% with full chromatographic profiles.
• Mass Spectrometry: ESI-MS/MALDI-TOF confirms molecular identity and C20 diacid modification.
• Amino Acid Analysis: Verifies correct 39-residue sequence composition.
• Endotoxin Testing: LAL assay <1 EU/mg.
• Fatty Acid Conjugation: LC-MS verification of C20 diacid attachment.
• Sterility Testing: Per USP standards for in vivo presentations.

Storage and Stability

Lyophilized Form

• Long-term: -20°C, protected from light. Shelf life 24+ months.
• Short-term: 2-8°C for up to 4 weeks.

Reconstituted Solution

• Vehicle: Bacteriostatic water or sterile PBS.
• Storage: 2-8°C for up to 14 days; aliquot and freeze at -20°C for longer storage.

Compliance and Intended Use

Research Use Only (RUO). Retatrutide supplied by Wholesale Bulk Peptides is intended solely for in vitro and preclinical research by qualified investigators. This product is not intended for human or veterinary use. Retatrutide is currently in clinical trials and has not been approved by any regulatory authority for any clinical indication.

Purchasers assume full responsibility for compliance with all applicable regulations.

Related Compounds

• Tirzepatide — Dual GIP/GLP-1 agonist, the immediate predecessor in multi-receptor agonist research.
• Semaglutide — Selective GLP-1 agonist benchmark compound for incretin research.
• MOTS-C — Mitochondrial peptide studied in metabolic and longevity research.

References

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. Cell Metab. 2022;34(9):1234-1247. PMID: 35320649
2. Jastreboff AM, Kaplan LM, Frias JP, et al. Triple-hormone-receptor agonist retatrutide for obesity — a phase 2 trial. N Engl J Med. 2023;389(6):514-526. PMID: 37351564
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-comparator-controlled, parallel-group, phase 2 trial. Lancet. 2023;402(10401):529-544. PMID: 37385280
4. Urva S, Coskun T, Loghin C, et al. The novel GIP, GLP-1 and glucagon receptor agonist retatrutide delays gastric emptying. Diabetes Obes Metab. 2023;25(9):2784-2788. PMID: 37243880

Frequently Asked Questions

What is retatrutide?

Retatrutide (LY3437943) is a first-in-class triple-hormone receptor agonist that activates GIP, GLP-1, and glucagon receptors simultaneously. It is a 39-amino-acid synthetic peptide with a C20 fatty diacid moiety providing an approximately 6-day half-life.

How does retatrutide differ from tirzepatide?

Tirzepatide is a dual GIP/GLP-1 agonist, while retatrutide adds glucagon receptor agonism as a third component. The glucagon component drives additional hepatic fat oxidation, increased energy expenditure, and enhanced weight loss in preclinical and clinical research.

What purity is guaranteed?

All retatrutide is supplied at 99%+ purity verified by RP-HPLC, with full analytical testing including mass spectrometry, amino acid analysis, fatty acid conjugation verification, and endotoxin testing.

Is retatrutide FDA-approved?

No. Retatrutide is currently in phase 3 clinical trials and has not been approved by any regulatory authority. Research-grade material from Wholesale Bulk Peptides is RUO only.

What research results have been published?

The phase 2 trial published in the New England Journal of Medicine (2023) reported mean body weight reductions of up to 24.2% at 48 weeks at the highest dose, with significant improvements in glycemic control and liver fat content. Phase 3 results are pending.

How should retatrutide be stored?

Lyophilized at -20C long-term (24+ months) or 2-8C short-term (up to 4 weeks). Reconstituted at 2-8C for up to 14 days, or aliquot and freeze.

What is the minimum order quantity?

Wholesale orders begin at 10 vials. Volume discounts range from 12% to 45% with custom pricing for orders exceeding 1,000 vials.

What vehicle should be used for reconstitution?

Bacteriostatic water or sterile PBS (pH 7.4). Gentle vortexing may be needed for complete dissolution due to the fatty acid modification.

What documentation is provided?

Batch-specific COA with HPLC purity, MS identity, amino acid analysis, endotoxin levels, fatty acid conjugation verification, and appearance data.

What is the lead time?

Standard orders ship within 3-5 business days. Bulk orders 7-10 business days. Expedited processing available.

Can retatrutide be used in comparative studies?

Yes. Retatrutide is commonly compared alongside semaglutide (single agonist) and tirzepatide (dual agonist) to systematically study the effects of increasing receptor agonism from single to triple.

Is retatrutide available as bulk powder?

Yes. Available in bulk quantities of 50 mg, 100 mg, and 500 mg in addition to standard vial formats. Custom quantities available for institutional accounts.