Evaluation of Physicochemical Properties and Biological Activity of Tirzepatide-Based Drugs

Currently, there is a steady increase in the prevalence of metabolic disorders among the population of developed countries. Among them, obesity and type 2 diabetes mellitus are the most important health problems. Tirzepatide is an innovative drug that is a dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors. The medcine is effective for the treatment of type 2 diabetes mellitus and obesity. The first drug with the active substance tirzepatide in Russia was Tirzetta® (manufacturer LLC «PROMOMED RUS»), which is the first in Russia, but not in the world. The reference drug for it is Munjaro® (INN: tirzepatide, Eli Lilly and Company, USA). To date, the question of the equivalence of these drugs has not been fully studied.

The aim. To conduct a comprehensive comparative evaluation of the reproduced drug Tirzetta® (INN: tirzepatide, manufacturer LLC “PROMOMED RUS”) and the reference drug Munjaro® (INN: tirzepatide, manufacturer Eli Lilly and Company, USA).

Materials and methods. The authenticity and quality of drugs were assessed by physicochemical methods according to the current pharmacopoeia of the EAEU. Spectrophotometry in the UV region, HPLC-MS/OF, and gel filtration chromatography were performed. The analysis of agonism to GIP and GLP-1 receptors was performed in vitro using reporter cell lines. The studies were performed in accordance with EMA, FDA, EAEU guidelines and in accordance with the current EAEU pharmacopoeia.

Results. As a result of the evaluation of the physicochemical properties of the studied series of Tirzetta® and the reference drug Munjaro®, it was found out that the absorption spectra in the ultraviolet region, the profile of related impurities and their quantitative content, the profile of high-molecular-weight compounds and their quantitative content, as well as mass spectra in all the studied series were similar. During the evaluation of the biological activity of the Tirzetta® and Munjaro® series, results were obtained that demonstrated the absence of statistically significant differences in the ability to activate GLP-1 and GIP receptors (p <0.0001). 

Conclusion. During the studies, the equivalence of the physicochemical properties and biological activity of the Russian drug Tirzetta® to the comparator drug Munjaro® was confirmed.

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