Description
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.
Uses 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.
Definition Mounjaro® and Ozempic® have distinct active ingredients: tirzepatide and semaglutide, respectively. However, both of these drugs are GLP-1 agonists, which bind to GLP-1 receptors, simulate a feeling of satiety, and signal the pancreas to produce insulin.
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.
Pharmacology Tirzepatide is a once-weekly GIP (glucose-dependent insulinotropic polypeptide) receptor and GLP-1 (glucagon-like peptide-1) receptor agonist that integrates the actions of both incretins into a single novel molecule. GIP is a hormone that may complement the effects of GLP-1 receptor agonists. In preclinical models, GIP has been shown to decrease food intake and increase energy expenditure therefore resulting in weight reductions, and when combined with GLP-1 receptor agonism, may result in greater effects on markers of metabolic dysregulation such as body weight, glucose and lipids.
Tirzepatide peptide is in phase 3 development for adults with obesity or overweight with weight-related comorbidity and is currently under regulatory review as a treatment for adults with type 2 diabetes. It is also being studied as a potential treatment for non-alcoholic steatohepatitis (NASH) and heart failure with preserved ejection fraction (HFpEF). Studies of tirzepatide in obstructive sleep apnea (OSA) and in morbidity/mortality in obesity are planned as well.
tirzepatide side effects
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%).
Synthesis
The synthesis process of tirzepatide is as follows: to a reactor was charged dichloromethane (28.6 kg), water (5.4 kg), DTT (4.3 kg), Boc-Fragment 1 + 2 + 3 + 4 (14.3 kg, 8), and TIPS (3.3 kg), resulting in a slurry. The slurry was cooled to less than 10 °C before TFA (162 kg) was added over no more than 1.75 h, resulting in a solution. The solution was warmed to 21 °C and held at this temperature for 3 h. The solution was transferred to a separate reactor, rinsing with TFA (54.3 kg). This solution was cooled to ?10 °C and charged MTBE (125.8 kg) over 2 h.
Then, additional MTBE (233 kg) was charged at 17 kg/h, maintaining an internal temperature of less than ?5 °C. The resulting slurry was warmed to 0 °C and then filtered. The wet cake was washed with MTBE (2 × 11 kg/kg relative to 8) and then dried under vacuum at no more than 35 °C to obtain tirzepatide (1, 8.71 kg, 1.81 mol, 81% yield).
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.
Pronunciation /tɜːrˈzɛpətaɪd/
tur-ZEP-ə-tyde
Trade names Mounjaro, Zepbound
Other names LY3298176, GIP/GLP-1 RA
Routes of administration Subcutaneous
Drug class Antidiabetic, GLP-1 receptor agonist
ATC code A10BX16 (WHO) QA10BX16 (WHO)
Bioavailability 80%
Protein binding Albumin
Metabolism Proteolytic cleavage, β-oxidation of fatty diacid section and amide hydrolysis
Elimination half-life 5 days
Excretion Urine and faeces
More Introduction:https://en.wikipedia.org/wiki/Tirzepatide
