Retatrutide Chemische Eigenschaften,Einsatz,Produktion Methoden
Beschreibung
Retatrutide is a novel triple agonist peptide of the glucagon receptor (GCGR), glucose-dependent insulinotropic polypeptide receptor (GIPR) and glucagon-like peptide-1 receptor (GLP-1R). Retatrutide inhibits human GCGR, GIPR and GLP-1R with EC50 values of 5.79, 0.0643 and 0.775 nM, respectively and mouse GCGR, GIPR, and GLP-1R with EC50 values of 2.32, 0.191 and 0.794 nM, respectively. It is an important tool for obesity research.
Retatrutide potently activates the GLP-1R signaling pathway to stimulate glucose-dependent insulin secretion through activity at the GIP receptor (GIPR) or the GLP-1R.
Retatrutide is a synthetic peptide with glucose-lowering effects. It is an antidiabetic agent against type 2 diabetes (T2D), stimulating insulin and suppressing glucagon secretion in a glucose-dependent manner.
Retatrutide was also shown to delay gastric emptying, lower fasting and postprandial glucose concentration, decrease food intake and reduce body weight in patients with type 2 diabetes.
History
Retatrutide (LY-3437943) was discovered by the American pharmaceutical company Eli Lilly and Company. It is a triple glucagon hormone receptor agonist (GLP-1, GIP, and GCGR receptors) for obesity. The 2024 Lasker~DeBakey Clinical Medical Research Award has been given to Joel Habener and Svetlana Mojsov for their discovery of a new hormone GLP-1(7-37) and to Lotte Knudsen for her role in developing sustained acting versions of this hormone as a treatment for obesity.
Biologische Aktivität
Retatrutide (LY3437943), a single peptide conjugated to a lipid diacid molecule, exerts a powerful agonist effect on the human glucagon‐receptor (GCGR), GIPR, and GLP‐1R. In comparison with the human glucagon and glucagon‐like peptide 1 (GLP‐1), retatrutide exhibits reduced potency (by a factor of 0.3 and 0.4, respectively) on the GCGR and GLP‐1R while displaying enhanced potency at the human GIPR (by a factor of 8.9) when compared to the glucose‐dependent insulinotropic polypeptide (GIP)[7].
Clinical claims and research
| Drug |
Target(s) |
Mechanism of Action |
Advantages |
Representative Clinical Outcomes |
| Semaglutide |
GLP-1 Receptor |
Mimics endogenous GLP-1 by delaying gastric emptying,
enhancing satiety, stimulating glucose-dependent insulin secretion,
and suppressing glucagon release.
|
Once-weekly administration, potent appetite suppression,
and proven cardiovascular protection.
|
Reduces the risk of major adverse cardiovascular events (MACE)
by approximately 26% and promotes significant weight loss.
|
| Tirzepatide |
GIP + GLP-1 Receptors |
Simultaneously activates GIP and GLP-1 receptors,
improving insulin secretion, glucose regulation,
and energy metabolism.
|
Superior glucose-lowering and weight-loss efficacy
compared with GLP-1 receptor agonists alone.
|
Demonstrated greater efficacy than semaglutide in head-to-head studies
and reduced the apnoea–hypopnoea index (AHI) by up to 62.8%
in patients with obstructive sleep apnoea.
|
| Mazdutide |
GLP-1 + GCGR Receptors |
Combines appetite suppression through GLP-1 receptor activation
with increased energy expenditure and lipid oxidation through
glucagon receptor activation.
|
Particularly beneficial for metabolic dysfunction-associated
steatotic liver disease (MASLD) and hyperuricaemia.
|
Reported fatty liver remission rates of approximately 41%,
alongside substantial weight reduction.
|
| Retatrutide |
GIP + GLP-1 + GCGR Receptors |
Simultaneously activates three metabolic pathways,
combining appetite suppression with enhanced calorie expenditure.
|
Currently among the most potent incretin-based therapies
for weight management.
|
Achieved mean weight loss of up to 28.7% at 68 weeks and
significantly improved obesity-related complications,
including knee osteoarthritis symptoms.
|
Retatrutide Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte
