Liraglutide is one of the analogues of the incretin hormone human glucagon-like peptide-1 (GLP-1) and is currently a priority treatment for diseases such as type 2 diabetes mellitus (mono- and combination therapy), obesity and overweight in the presence of at least one concomitant disease.The aim of the work was to assess the bioequivalence and comparability of the safety and tolerability profile of the drug Enligria® (liraglutide 6 mg/ml, Promomed RUS LLC, Russia) and the drug Saxenda® (liraglutide 6 mg/ml, Novo Nordisk AS, Denmark) after a single dose in healthy volunteers.Materials and methods. This study was an open-label, randomized, crossover comparative study to evaluate pharmacokinetic parameters, safety, tolerability and immunogenicity. The study comprised 26 healthy volunteers, 26 of whom were included in the bioequivalence assessment population. The study consisted of 2 periods, in each of which the volunteers received either the test drug (liraglutide at a single dose of 0.6 mg) or the reference drug (liraglutide at a single dose of 0.6 mg) once. The washout period between each dose was 7 days. Blood plasma samples were taken to determine the concentration of liraglutide in the range from 0 to 72 hours in each study period. Liraglutide concentrations were determined using a previously validated enzyme-linked immunosorbent assay (ELISA) method. A quantitative determination of antibodies to liraglutide in the blood serum samples was carried out using a microplate photometer and ready-made ELISA kits pre-validated by the manufacturer. The conclusion about the equivalence of the compared drugs was made based on the ratio of the parameters C_max, AUC_0→t and AUC_0→t of the studied drug in relation to the reference one.Results. The pharmacokinetic parameters of the drugs were comparable to each other. The resulting 90% confidence intervals for the ratio of the values of C_max, AUC_0-t and AUC_0-∞ of the Russian test and reference drug were 87.18–110.46, 84.40–104.11 and 86.69–103.22% respectively, which satisfied the criteria for assessing bioequivalence. The tolerability of the drugs in the volunteers was notified as good. The incidence of adverse events was comparable for the test and reference drugs. No serious adverse events were reported throughout the study. According to the results of the immunogenicity analysis, no antibodies to russian produced liraglutide were detected in the blood serum of the volunteers, which indicated the lack of the drug immunogenicity.Conclusion. During the study, the pharmacokinetic equivalence of the test and reference drugs was confirmed. The Russian drug Enligria® (liraglutide 6 mg/ml, Promomed RUS LLC, Russia) in comparison with a foreign drug Saxenda® (liraglutide 6 mg/ml, Novo Nordisk AS, Denmark).

Semaglutide is a representative of analogues of the incretin hormone human glucagon-like peptide-1 (GLP-1) and is currently used in Russia for the treatment of type 2 diabetes mellitus (T2DM; in monotherapy and in combination therapy), including patients with obesity and overweight.The aimof the work was to conduct a comparative assessment of the physicochemical properties, a biological activity, bioequivalence and safety, including tolerability and immunogenicity, of the drug Quincent® (semaglutide, 1.34 mg/ml, a solution for a subcutaneous administration, Promomed Rus LLC, Russia) and the drug Ozempic® (semaglutide, 1.34 mg/ml, a solution for a subcutaneous administration, Novo Nordisk A/S, Denmark) when administered to healthy volunteers.Materials and methods.To assess the degree of similarity of the study drug Quincenta®(semaglutide, 1.34 mg/ml, a solution for a subcutaneous administration, Promomed Rus LLC, Russia) with a chemically synthesized active substance to the original (reference) drug Ozempic® (semaglutide, 1.34 mg/ml, a solution for a subcutaneous administration, Novo Nordisk A/S, Denmark), a comparative study of physicochemical properties and a biological activity was carried out. To assess the bioequivalence of the study drug and the reference drug, an open randomized parallel comparative study with the participation of healthy volunteers (n=54), 54 participants of which had been included in the population, was conducted. The volunteers were randomized into 2 groups in a 1:1 ratio, and received a single dose subcutaneously either of the study drug (domestic semaglutide at a dose of 0.5 mg) or the reference drug (foreign semaglutide at a dose of 0.5 mg). The mode of administration was in the morning on an empty stomach. A semaglutide concentration was determined in serum samples using a previously validated enzyme-linked immunosorbent assay (ELISA) method. A quantitative determination of antibodies to semaglutide in the human serum by ELISA was carried out with a microplate photometer using ready-made kits pre-validated by the manufacturer. The conclusion about the bioequivalence of the compared drugs was made using an approach based on the assessment of 90% confidence intervals for the ratios of the geometric mean values of the parameters C_max, AUC_(0–t)of semaglutide in the measurement original units.Results.The results of the comparative analysis of the study drug and the reference drug demonstrate the comparability of their physicochemical properties and biological activity. The results of the clinical study demonstrated the bioequivalence of the test drug and the reference drug. Thus, the pharmacokinetic parameters of the drugs were comparable to each other: the C_maxvalue for the study drug was 42.088±8.827 ng/ml, for the reference drug Ozempic® it was 42.2556±7.84. Herewith, the half-life for the study drug and the reference drug was 168.39±39.47 and 157.99±28.57 hours, respectively. The resulting 90% confidence intervals for the ratio of the C_maxand AUC_0–tvalues of the study drug and the reference drug were 90.89–109.15 and 91.66–111.27%, respectively. The tolerability of the drugs in the volunteers was notified as good. No adverse events were recorded during the study. No serious adverse events were reported throughout the study. According to the results of the immunogenicity analysis, no antibodies to Russian-made semaglutide were detected in the blood serum of the volunteers, which indicated the lack of Results. The results of a comparative analysis of the study drug and the reference drug demonstrate the comparability of physicochemical properties and biological activity. The results of the clinical study demonstrated the bioequivalence of the study drug and the reference drug. Thus, the pharmacokinetic parameters of the drugs were comparable to each other: the C_maxvalue for the study drug was 42.088±8.827 ng/ml, for the reference drug Ozempic® this figure was 42.2556±7.84. At the same time, the half-life for the study drug and the reference drug was 168.39±39.47 and 157.99±28.57 hours, respectively. The resulting 90% confidence intervals for the ratio of the C_maxand AUC_0–tvalues of the study drug and the reference drug were 90.89–109.15 and 91.66–111.27%, respectively. Tolerability of the drugs in volunteers was noted as good. No adverse events were recorded during the study. No serious adverse events were reported throughout the study. According to the results of the immunogenicity analysis, no antibodies to Russian-made semaglutide were detected in the blood serum of the volunteers, which indicated the lack of the drug immunogenicity.Conclusion.In the course of the study, the comparability of the physicochemical properties and biological activity of the studied Russian drug with the chemically synthesized active substance Quincenta® to the reference drug Ozempic® was confirmed: the activity range of the studied drugs was within 80–120% in relation to the standard sample of semaglutide. The bioequivalence and a similar safety profile, including the immunogenicity and tolerability of the Russian drug Quincenta® (semaglutide 1.34 mg/ml, Promomed Rus LLC, Russia) were shown in comparison with the foreign drug Ozempic® (semaglutide 1.34 mg/ml, Novo Nordisk A/C, Denmark).

Today, there is an annualincrease in the prevalence of obesityandoverweightworldwide.Thisproblem is becomingparticularlyrelevant,sincetheseconditionsserve as keyriskfactors for the development of anumber of cardiovascularandmetabolicdisorders,including type 2diabetesmellitus(T2DM).On the territory of the Russian Federation, drugswerepresentedasagonists of glucagon-like peptide of the first type (GLP-1)receptors, the activesubstance of which was producedexclusively by biotechnologicalmeans. It is important to notethat solid-phasechemicalsynthesisisalsooneof the alternativemethods for obtainingGLP-1analogues. A significantadvantage of thismethodoverbiotechnologicalsynthesisis the exclusion of spontaneousamino acid substitutionsand the absence of impuritiescharacteristicofthismethod.The aim. Evaluation of the biological activity of the domestic medicinal product liraglutide (Enligria^®, solution for subcutaneous administration, 6 mg/ml, PROMOMED RUS LLC), obtained by chemical synthesis, and a foreign reference drug (Saxenda^®,solutionforsubcutaneousadministration,6 mg/ml,NovoNordiskA/C),obtainedbiotechnologically.Materials and methods. The effectiveness of liraglutide preparations was evaluated using a model of induced metabolic syndrome in CBA×C57BL/6 SPF mice (n=36,age6months)according to changes in body weight,feedintake,bloodglucoseandlipid levels, and adiposetissuemass.Results. According to the results of the study, it was shown that Enligria^® and Saxenda^® drugs have comparable efficacy parameters and statistically significantly (p < 0.05) reduce body weight (13.6±2.1% and 13.3±3.3%, respectively), glucose levels (18 ± 3% and 16 ± 9%), triglycerides (32 ± 12% and 40 ± 18 %) and cholesterol (16 ± 7% and 18 ± 9%) in the blood. Enligria^® reduced the mass of structural subcutaneous fat by 32 ± 3% (p < 0.0001), and visceral fat by 34 ± 4% (p < 0.0001). The studiedliraglutidepreparationsshowed a pronouncedhypoglycemiceffect,observedinalldoseranges. The observedhypoglycemiceffectwasdose-dependent.Conclusion. The results of the work indicate the high effectiveness of the synthetic drug Enligria^®, which is expressed in reducing body weight and improving metabolic parameters.

One of the new classes of drugs for weight loss in overweight and obesity, the safety and efficacy of which have been proven in large-scale studies, are glucagon-like peptide-1 receptor agonists (GLP-1 agonists). Separately, it is worth highlighting the main representative from the GLP-1 agonists class, semaglutide. At a dose of 2.4 mg, this drug demonstrated clinically significant results in terms of the body weight reduction and improvement of cardiometabolic health.The aim of the work was to evaluate pharmacokinetic parameters, bioequivalence, safety, tolerability and immunogenicity of the Velgia® (WRYC12301) at doses of 0.25 mg (0.68 mg/ml) and 2.4 mg (3.2 mg/mL) in comparison with the reference drug Wegovy® (Novo Nordisk A/S, Denmark) at the doses of 0.25 mg (0.68 mg/mL) and 2.4 mg (3.2 mg/mL).Materials and methods. The study was conducted between March and June 2024. The volunteers (n=60) were randomised into 4 groups (n=15 in each) in a 1:1 ratio to study the semaglutide dosages of 0.25 mg/dose (0.68 mg/mL) in Groups 1, 2 and 2.4 mg/dose (3.2 mg/mL) in Groups 3, 4. The study drug and the reference drug were injected subcutaneously into the anterior abdominal wall. Pharmacokinetic parameters, bioequivalence, safety, tolerability and immunogenicity of semaglutide (solution for subcutaneous administration, JSC Biochemik, Russia) were studied. Some parameters regulating the quality of the active pharmaceutical substance semaglutide, were determined.Results. The obtained 90% confidence intervals (CIs) for the ratio of C_max and AUC_(0-t) values of the study and reference drugs (Groups 1, 2) at a dose of 0.25 mg (0, 68 mg/mL) were 85.19–114.36% for C_max and 81.35–112.60% for AUC_(0-t), respectively, while for Groups 3, 4, at a dose of 2.4 mg (3.2 mg/mL), C_max was 83.18–111.3% and AUC_(0-t) was 91.70–120.89%, respectively. The obtained 90% CI lies within the established limits, which confirms the bioequivalence of the study and reference drugs. All adverse events registered during the study were of mild severity. According to the results of the immunogenicity parameters analysis, no antibodies to semaglutide were detected in the serum of volunteers.Conclusion. In the course of the study, the bioequivalence of the study and reference drugs was confirmed. A high safety profile and absence of immunogenicity were demonstrated for the Russian drug Velgia® (WRYC12301, semaglutide, solution for a subcutaneous administration, JSC Biochemik, Russia) in comparison with the reference drug (semaglutide, solution for a subcutaneous administration, Novo Nordisk A/S, Denmark) in doses of 0.25 mg/dose (0.68 mg/mL) and 2.4 mg/dose (3.2 mg/mL).

The aim. To conduct a comparative evaluation of the physicochemical properties, biological activity, bioequivalence, and safety, including tolerability and immunogenicity, of the drug Semaltara® (semaglutide, tablets 3 and 14 mg (Biochemik, Russia) and the drug Rebelas® (semaglutide, tablets in dosages of 3 and 14 mg (Novo Nordisk A/S, Denmark) when administered to healthy volunteers. Materials and Methods. To assess the bioequivalence of the investigational drug Semaltara® (semaglutide, tablets 3 and 14 mg (Biochemik, Russia) with a chemically synthesized active substance to the original (reference) drug Rebelas® (semaglutide, tablets in dosages of 3 and 14 mg (Novo Nordisk A/S, Denmark), an open-label randomized crossover comparative study ( n = 110) was conducted. Patients were randomized into 4 groups: Group 1 ( n = 25) — patients received the investigational drug Semaltara® and the comparator drug Rebelas® daily once a day at a dose of 3 mg (1 tablet) for 28 days; Group 2 ( n = 25) — the comparator drug Rebelas® and the investigational drug Semaltara® daily once a day at a dose of 3 mg (1 tablet) for 28 days; Group 3 ( n = 30) — the investigational drug Semaltara® and the comparator drug Rebelas® daily once a day at a dose of 14 mg (1 tablet) for 28 days; Group 4 ( n = 30) — the comparator drug Rebelas® and the investigational drug Semaltara® daily once a day at a dose of 14 mg (1 tablet) for 28 days. The concentration of semaglutide was determined in serum samples using a pre-validated enzyme-linked immunosorbent assay (ELISA) method. The conclusion on bioequivalence of the compared drugs was made based on the assessment of 90 % confidence intervals for the ratios of geometric mean values of C _max and AUC _(0–t) parameters of semaglutide in the original units of measurement. Results. The results of the clinical study demonstrated the bioequivalence of the investigational drug and the comparator drug. The pharmacokinetic parameters of the drugs were comparable: Based on statistical analysis, the obtained 90 % confidence intervals for the ratio of C _max,ss and AUC _{(0- τ )ss} values of semaglutide 3 mg were 96.57–120.94 % and 94.37–120.06 %, respectively. For the 14 mg dosage, the 90 % confidence intervals for the ratio of C _max,ss and AUC _{(0- τ )ss} values of semaglutide were 91.79–109.68 % and 91.47–112.80 %, respectively. The tolerability of the drugs in volunteers was noted as good. No serious adverse events were registered during the entire study. Thus, the investigational drug Semaltara®, tablets, and the comparator drug Rebelas®, tablets, have a similar safety profile, including tolerability, at both the 3 mg and 14 mg dosages. Conclusion . The conducted study demonstrated the bioequivalence and similar safety profile, as well as tolerability of the Russian drug Semaltara® (semaglutide 3 and 14 mg, tablets, Promomed LLC, Russia) in comparison with the foreign drug Rebelas® (semaglutide, tablets in dosages of 3 and 14 mg (Novo Nordisk A/S, Denmark).