Comparative study of the efficacy and safety of tirzepatide drugs in metabolic syndrome

In the last decade, developed countries have seen a steady increase in the prevalence of metabolic disorders. The most significant among them are obesity and type 2 diabetes mellitus. Tirzepatide is an innovative drug, representing the first-in-class dual agonist of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors. Tirzepatide combines the action of two key incretin hormones, providing more comprehensive and effective regulation of glycemia and metabolism compared to traditional GLP-1 monoagonists. Tirzepatide was unavailable in Russia for a long time. However, in 2025, the first domestically produced tirzepatide drug, Tirzetta® (LLC “PROMMOMED RUS”), appeared. The aim. To conduct a comparative evaluation of the efficacy and safety of the reproduced drug Tirzetta® (INN: Tirzepatide, manufacturer LLC “PROMMOMED RUS”) and the reference drug Mounjaro® (INN: Tirzepatide, manufacturer “Eli Lilly”) in a mouse model with induced metabolic syndrome (MS). Materials and methods. The study was conducted on male mice of the C57BL/6 line. To metabolic syndrome (MS) was induced in animals with a diet high in fat and carbohydrates. Three batches of Tirzetta® and one series of Munjaro® were investigated. The drugs were administered at a dosage of 150 µg/kg subcutaneously once every three days for 15 days. During the experiment, glucose tolerance and insulin sensitivity tests were performed. The type of metabolism was determined by indirect calorimetry data. Mice were euthanized on 25th day for humane reasons upon reaching any of the following criteria: body weight loss of more than 15% in a week; serious injuries (fractures, amputations, etc.), appearance of non-healing wounds; seizures; unconscious state. A complete blood count was performed, and the following parameters were determined: glucose, triglycerides, cholesterol, AST, ALT. Necropsy was performed after euthanasia. During necropsy, the thoracic and abdominal organs of the animals were examined, and organs were dissected and weighed. Results. In the MS group animals, body weight increased to 39.5 ± 0.6 g compared to the control group (31.9 ± 0.6 g), representing a 24% increase. Significant hyperglycemia was recorded with a glucose concentration of 14.9 ± 2.7 mmol/L versus 6.1 ± 0.4 mmol/L in the control, as well as a pronounced decrease in glucose tolerance in the loading test. The investigated tirzepatide drugs demonstrated a pronounced hypophagic effect with a 26–28% reduction in body weight, normalization of glycemia with a 48–53% decrease in glucose concentration, and improvement in glucose tolerance and insulin sensitivity. Indirect calorimetry data indicated a decrease in the respiratory exchange ratio, suggesting lipolysis activation. A significant reduction in triglyceride content in blood serum and liver was revealed. The bioequivalence of the investigated drugs Tirzetta® and Mounjaro® was established in the experimental MS model in mice based on a set of therapeutic efficacy and safety indicators. Conclusion . Studies on an experimental model of induced MS in mice showed equivalent efficacy of Tirzetta® (INN: Tirzepatide, manufacturer LLC “PROMMOMED RUS”, Russia) and Mounjaro® (INN: Tirzepatide, manufacturer “Eli Lilly”, USA).