Tirzepatide Chemische Eigenschaften,Einsatz,Produktion Methoden
Beschreibung
Tirzepatide (LY3298176) was developed as a dual agonist to both GLP-1 and gastric inhibitory polypeptide (GIP) receptors (Frias et al., 2018). Similar to GLP-1, GIP is an incretin hormone that functions to induce insulin secretion.
History
Tirzepatide is a 39-amino acid synthetic peptide developed by Eli Lilly and Company. Its design is based on the sequence of a natural glucose-dependent insulinotropic polypeptide (GIP) and simultaneously activates the glucagon-like peptide-1 (GLP-1) receptor, hence the name "twincretin." The drug first entered clinical research in 2016, with Eli Lilly initiating a Phase I clinical trial to evaluate its safety, tolerability, pharmacokinetics, and pharmacodynamics in obese or overweight subjects with related comorbidities. Subsequently, a Phase II trial further clarified its dose-response relationship and demonstrated significant blood glucose-lowering and weight-loss effects. Phase III clinical trials, including the SURPASS and SURMOUNT series, covered comparisons with placebo and active control drugs (such as semaglutide, insulin glargine, and insulin degludec), confirming its superior efficacy in the treatment of type 2 diabetes and obesity. In May 2022, Tirzepatide, marketed under the brand name Mounjaro®, was approved by the U.S. FDA for the treatment of type 2 diabetes, becoming the first and only approved GIP/GLP-1 dual receptor agonist . Subsequently, the drug was approved under the brand name Zepbound® for weight management. Throughout the development process, Eli Lilly remained the sole original developer of the drug, and no individual scientists specifically involved in the drug design have been disclosed in publicly available literature. The structure of Tirzepatide extends its half-life to approximately 5 days by introducing α-aminoisobutyric acid (Aib) to replace alanine at positions 2 and 13 to prevent DPP-4 degradation, and by covalently binding to a C20 eicosanedioic acid via a γGlu-(AEEA-AEEA) linker at position 20 lysine residue, enabling once-weekly dosing.
Verwenden
Tirzepatide is used with a proper diet and exercise program to control high blood sugar in people with type 2 diabetes. Controlling high blood sugar helps prevent kidney damage, blindness, nerve problems, loss of limbs, and sexual function problems.
Handelsname
brand name: Mounjaro
Mechanism of action
It works to stimulate first- and second-phase insulin secretion, and reduces glucagon levels, both in a glucose-dependent manner. Tirzepatide was also shown to delay gastric emptying, lower fasting and postprandial glucose concentration, decrease food intake, 4 and reduce body weight in patients with type 2 diabetes.
Nebenwirkungen
The overall safety and tolerability profile of tirzepatide was similar to other incretin-based therapies that have been approved for the treatment of obesity. This said, reported side effects were considerable, especially as dosage levels increased. The most common adverse events were nausea (~30%), diarrhea (~20%), constipation (~15%) and vomiting (~10%).
If tirzepatide gets approved as a both a blood glucose control and anti-obesity agent, it could become a blockbuster drug. However, this isn’t a sure thing. It will have to overcome pricing and reimbursement obstacles, which have plagued similar treatments.
Clinical claims and research
Tirzepatide (Eli Lilly), a novel, once-weekly injectable dual glucose-dependent insulinotropic polypeptide (GIP) receptor and GLP-1 RA combination drug, has been developed to treat patients with T2DM. The manufacturer (Eli Lilly) announced the submission of a biologics license application with priority review to the FDA for T2DM on October 27, 2021, with a decision expected in mid-2022.
Research
Tirzepatide is in phase 3 clinical development at Eli Lilly and Company for blood glucose management in adults with type 2 diabetes, chronic weight management, and obesity-related heart failure with preserved ejection fraction. In addition, Tirzepatide is being studied as a potential treatment for non-alcoholic steatohepatitis (NASH). The molecule comprises a 39 amino acid peptide backbone and a side chain at residue 20. Of the 39 amino acids, 37 are naturally occurring (or coded), while two are noncoded aminoisobutyric acid residues at positions 2 and 13[1].
Tirzepatide Upstream-Materialien And Downstream Produkte
Upstream-Materialien
Downstream Produkte
