Injectable therapy in type 2 diabetes mellitus: strategies to improve therapeutic adherence
Abstract: In recent years, the options in treatment of diabetes mellitus type 2 have substantially expanded (currently more than 40 molecules are approved), however, the number of patients with decompensation of diabetes for the period from 2003 to 2014 remains unchanged. In clinical guidelines injecting drugs are given the final role as the most effective drugs. However in clinical trials injecting drugs showed a lower adherence compared to oral drugs. Currently injectable glucose lowering drugs include not only insuli… Show more
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Comparative analysis of physicochemical properties, bioequivalence, safety and tolerability of the first domestic semaglutide
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 aim of 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 Cmax, 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 Cmax value 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 Cmax and AUC0–t values 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 Cmax value 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 Cmax and AUC0–t values 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).
Comparative analysis of physicochemical properties, bioequivalence, safety and tolerability of the first domestic semaglutide
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 aim of 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 Cmax, 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 Cmax value 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 Cmax and AUC0–t values 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 Cmax value 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 Cmax and AUC0–t values 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).
In the clinical practice of an endocrinologist, verification of the type of diabetes mellitus (DM) in young people is of high clinical significance, since the prescription of treatment depends on this: from the correction of carbohydrate metabolism by a balanced diet to the prescription of oral hypoglycemic drugs and insulin therapy. In rare forms of diabetes mellitus, which include «latent autoimmune diabetes in adults» (LADA), it is not always possible to make a correct diagnosis. This form of diabetes mellitus occupies an intermediate position between type 1 diabetes mellitus and type 2 diabetes mellitus (DM 1 and DM 2) and is often not detected. In this regard, the study of the LADA flow is of great practical importance. Verification of the LADA diagnosis is based on three clinical criteria: adult onset of diabetes; the presence of circulating islet autoantibodies, which distinguishes LADA from T2DM; the absence of an absolute need for insulin when making a diagnosis, which distinguishes LADA from the classic type 1 diabetes mellitus. The main treatment tactics for patients with LADA should be aimed at preserving their own insulin secretion. This requires the timely appointment of insulin therapy. The question of the possibility of using drugs of peripheral action – biguanides and glitazones, which do not cause depletion of β-cells, is discussed, but their effectiveness has not yet been established. The appointment of any secretogens, including sulfonylurea preparations, is contraindicated Quite often, LADA is difficult to diagnose, and the wrong treatment tactics are prescribed. At the moment, there is little data on the effectiveness of different classes of drugs, which leads to further detailed study of this type of diabetes. Currently, there are no special algorithms for LADA treatment
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