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Products Description
Retatrutide (LY3437943) acetate is a triple agonist peptide for the glucagon receptor (GCGR), glucose-dependent insulinotropic polypeptide receptor (GIPR), and glucagon-like peptide-1 receptor (GLP-1R).
Retatrutide acetate inhibits human GCGR, GIPR, and GLP-1R with EC50 values of 5.79, 0.0643, and 0.775 nM, respectively. It exhibits activity on mouse GCGR, GIPR, and GLP-1R with EC50 values of 2.32, 0.191, and 0.794 nM, respectively.
In vivo, Retatrutide (LY3437943) acetate engages with GCGR and enhances glucose tolerance in an ipGTT by acting through GIP or GLP-1 receptors. Activation via the glucagon receptor by Retatrutide acetate leads to significant weight reduction and increased energy expenditure. Retatrutide acetate can be utilized in research related to obesity.
Retatrutide is a new type of multi-target peptide drug developed by Eli Lilly and Company of the United States, it is a trip
le receptor agonist of GLP-1R/GIPR/GCGR. Its core mechanism is to regulate the metabolic process by activating glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and glucagon (GCG) receptors at the same time, and is used for the treatment of obesity and type 2 diabetes. The following are its key features:
| Items | Specifications |
|---|---|
| Product Name | Retatrutide |
| CAS No. | 2381089-83-2 |
| Molecular Formula | C187H291N45O59 |
| Appearance | White Powder |
| Packaging | 10mg/vial, 10vials/box |
| MOQ | 10 vials |
Mechanism of Action and Molecular Structure of Retatrutide:
1)Triple Agonist Design
- GLP-1 receptor: Retatrutide delays gastric emptying, suppress appetite, and promote insulin secretion.
- GIP receptor: Retatrutide enhances insulin sensitivity and regulate central satiety signals.
- Glucagon receptor (GCGR): Retatrutide activates liver energy metabolism, promote lipolysis and glycogenolysis, and increase basal metabolic rate.
The triple synergistic effect increases energy consumption while reducing energy intake, significantly improving weight loss effects.
2) Structural Optimization
- Based on the GIP skeleton modification, non-natural amino acids (such as α-methylleucine at position 13) are introduced to enhance receptor affinity.
- The half-life is extended to 7 days through fatty acid side chain modification, supporting subcutaneous injection once a week.
Clinical Effects and Core Data of Retatrutide:
1) Outstanding Weight Loss Effect:
- 48 weeks of treatment: The average weight loss in the 12mg dose group reached 24.2%, significantly better than existing drugs (such as Semaglutide and Tirzepatide).
- Gender differences: Women have a more significant weight loss effect (28.5% vs. men 21.2%).
- Dose dependence: From the starting dose of 2mg to 12mg, the weight loss ratio increases with the dose.
Comparison of Weight Loss Effects at Different Doses (48-Week Data):
| Doses | 4mg | 8mg | 12mg |
| Weight Loss Ratio | ~8.7% | ~17.5% | ~24.2% |
| Waist Circumference Reduction | -2.1cm | -6.1cm | -10.2cm |
Before and after weight loss：
2) Comprehensive Improvement of Metabolism:
- Blood sugar control: Significantly reduce glycated hemoglobin (HbA1c), and doses above 4mg are better than dulaglutide.
- Cardiovascular metabolism: Improve triglyceride, cholesterol and blood pressure levels, potentially reducing cardiovascular risks.
- Expanded indications: Used in research for metabolic-related diseases such as polycystic ovary syndrome (PCOS).
Indications and Efficacy
★ Obesity Treatment:
In the Phase II clinical trial, patients in the highest dose group (12 mg) lost an average of 24.2% weight after 48 weeks, and some patients lost more than 30%.
★ Type 2 Diabetes:
Significantly reduce glycated hemoglobin (HbA1c) and improve blood sugar control.
★ Metabolic Dysfunction-Associated Fatty Liver Disease (MASLD):
Retatrutide can reduce liver fat content by 86%, and more than 85% of patients achieve regression of liver steatosis.
★ Potential Cardiovascular Benefits:
Animal studies have shown that it may indirectly protect cardiovascular health by improving blood pressure and heart function, but further clinical verification is needed.
Market Prospects and Challenges:
◎ Differentiation Advantages:
Compared with existing GLP-1 single-target (such as Semaglutide) or dual-target drugs (such as Tirzepatide), the triple mechanism of Retatrutide has greater potential in weight loss and metabolic improvement.
◎ Cost and Accessibility:
Currently, the production cost of peptide drugs is relatively high, but the long-acting properties of Retatrutide may reduce the frequency of medication and improve patient compliance.
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