Retatrutide
Triple GLP-1/GIP/Glucagon agonist — up to -24.2% body weight over 48 weeks
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About Retatrutide
Retatrutide (LY3437943) is a novel triple agonist that simultaneously activates the GLP-1, GIP and glucagon receptors. Developed by Eli Lilly, this peptide represents a paradigm shift in obesity research, being the first molecule to engage three incretin-based signaling pathways at once. The glucagon component fundamentally distinguishes Retatrutide from dual agonists such as Tirzepatide: while GLP-1 and GIP synergistically enhance satiety and improve insulin sensitivity, glucagon receptor activation increases hepatic energy expenditure through elevated lipid oxidation and thermogenesis. In the randomized, double-blind Phase II trial by Jastreboff et al. (New England Journal of Medicine, 2023; n=338), subjects on the highest dose (12 mg weekly) achieved a mean weight reduction of -24.2% after 48 weeks — the strongest effect ever documented in clinical trials for a single peptide. As early as 24 weeks, reduction reached -17.5%, highlighting rapid pharmacokinetics. At the molecular level, Retatrutide binds the GLP-1 receptor with low-nanomolar affinity (EC50 ~0.1 nM), while GIP and glucagon receptor activation ratios were optimized to maximize metabolic synergy. Preclinical data from Coskun et al. (Cell Metabolism, 2022) show up to 80% reduction in liver fat content in mouse models and significant improvement of hepatic steatosis markers ALT and AST. Phase III trials under the TRIUMPH program are currently underway across more than 45 centers worldwide, enrolling over 4,000 subjects. The peptide is supplied as lyophilized powder and must be reconstituted in bacteriostatic water prior to use. The amino acid sequence comprises 39 residues with a C18 fatty-acid modification that extends plasma half-life to approximately 6 days, enabling once-weekly dosing.
Specifications
- Mean weight reduction of -24.2% after 48 weeks in Phase II trial (Jastreboff et al., NEJM 2023, n=338)
- Triple receptor activation at GLP-1, GIP and glucagon simultaneously — unique among incretin-based therapies
- Significant reduction of hepatic steatosis up to 80% in preclinical models (Coskun et al., Cell Metabolism 2022)
- HbA1c improvement of -1.3% and fasting glucose reduction of -18% in the highest dosage group
- Increased energy expenditure via hepatic lipid oxidation and thermogenesis through glucagon receptor activation
- Extended plasma half-life of ~6 days via C18 fatty-acid modification — once-weekly dosing
- Reduction of systolic blood pressure by -7.2 mmHg and triglycerides by -30% in post-hoc analysis
- Over 90% of subjects in the 12-mg group achieved ≥5% weight reduction after 48 weeks
- Phase III TRIUMPH program (NCT05929066) launched with 4,000+ subjects at 45+ centers worldwide
- Rapid onset: -17.5% weight reduction already after only 24 weeks of treatment
Research context
The central publication is Jastreboff et al., "Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial", New England Journal of Medicine, Volume 389, Pages 514–526 (2023), DOI: 10.1056/NEJMoa2301972. This randomized, double-blind, placebo-controlled study enrolled 338 adults with BMI ≥30 (or ≥27 with comorbidities) over 48 weeks across 25 U.S. centers. Complementary data from Coskun et al., "LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist for glycemic control and weight loss", Cell Metabolism, Volume 34, Pages 1234–1247 (2022), DOI: 10.1016/j.cmet.2022.07.013, elucidate the molecular mechanisms of triple receptor binding and preclinical efficacy. Phase III trials in the TRIUMPH program (NCT05929066, NCT05929079) have been ongoing since Q3 2023 across 45+ centers worldwide, evaluating Retatrutide at 4 mg, 8 mg and 12 mg weekly. Preclinical work from Finan et al. in Nature Metabolism (2020) documents the role of the glucagon component in hepatic lipid oxidation and thermogenesis, with up to 80% reduction in liver fat content in mouse models. A post-hoc analysis of Phase II data shows significant improvements in cardiovascular risk factors, including systolic blood pressure (-7.2 mmHg), triglycerides (-30%) and hsCRP (-42%).
Storage & handling
Temperature
-20°C (lyophilized) / 2–8°C (reconstituted)
Conditions
Protect from direct light and moisture
Shelf life
18 months (lyophilized, sealed vial)
Reconstitution of Retatrutide
Solvent
Bacteriostatic water (0.9% benzyl alcohol)
Volume
1–2 mL
Concentration
10 mg/mL at 1 mL, 5 mg/mL at 2 mL
Step-by-step
- 1Allow the vial and bacteriostatic water to reach room temperature (15–20 minutes).
- 2Use an alcohol swab to disinfect the rubber stoppers of both the peptide vial and the water vial.
- 3Draw the desired amount of bacteriostatic water (1–2 mL) using a sterile 1-mL insulin syringe.
- 4Place the needle against the side of the vial and let the water run slowly down the inner wall — never spray directly onto the lyophilized powder.
- 5Gently swirl the vial or roll it between your palms until the powder is fully dissolved. Never shake, as this can denature the peptide structure.
- 6Visually inspect the clear solution for particulates. Do not use if cloudy or if visible particles are present.
- 7Store reconstituted Retatrutide immediately at 2–8°C in the refrigerator and use within 28 days.
- 8Disinfect the rubber stopper and use a fresh sterile syringe for every withdrawal.
Frequently asked questions
What is Retatrutide and how does it work?
Retatrutide (LY3437943) is a triple agonist that simultaneously binds the GLP-1, GIP and glucagon receptors. In Phase II clinical trials, mean weight reduction of up to 24.2% was documented after 48 weeks — the strongest effect ever published for a single peptide.
How is Retatrutide reconstituted?
The lyophilized powder is reconstituted with bacteriostatic water. Inject the water slowly against the inner wall of the vial and swirl gently — never shake, as this can damage the peptide structure.
How is Retatrutide stored?
Store lyophilized at -20°C. After reconstitution, keep refrigerated at 2–8°C and protect from direct light. Shelf life is 18 months in the sealed vial.
What is the purity of Retatrutide?
Our Retatrutide is supplied at >99% purity (HPLC-verified). Every batch undergoes strict quality control to confirm the identity and purity of the peptide.
Is Retatrutide available for research in the US?
Retatrutide is available as a research chemical for scientific purposes. It is not an approved drug and is intended exclusively for in-vitro research.
Customer reviews
Received lot with clean HPLC trace on request — vial sealed under vacuum, perfect lyophilization cake, reconstituted clear with no particulates. Consistent with peer-reviewed specs.
Dr. M. — independent research lab
Second order of retatrutide from OXpeptides. Packaging plain and discreet as promised, transit 4 days to US Midwest. COA matched lot number. No complaints.
R. K. — metabolic research group
Strong product, full documentation. Would prefer cold-shipment option on warmer months but sealed lyophilized vial arrived intact. Happy overall.
S. H. — academic researcher
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