Effectiveness prediction of Evogliptin treatment in type 2 diabetes mellitus in russian-korean population

Background: Individualized treatment has already become a part of a routine clinical care. Many data on the effectiveness prediction of commercially available DPP-4 inhibitors had been published, but not on the effectiveness prediction of evogliptin. Aim: To reveal the clinical characteristics and metabolic predictors of better hypoglycemic response to evogliptin. Matherials and methods: We have conducted a retrospective study, based on the data of a randomized clinical trial comparing effectiveness and safety of evogliptin and sitagliptin in Russian and Korean subpopulations. We provide univariate linear regression models for separate subpopulations and a multivariate stepwise regression model for the combined subpopulation. HbA1c change after 24 weeks of evogliptin treatment was a primary endpoint and a dependent variable in the analysis. Results: The decrease of HbA1c after 24 weeks of treatment with evogliptin in Russian subpopulation negatively correlates with triglycerides/HDL level (p = 0,046). In South Korean subpopulation it correlates positively with HbA1c level at baseline (p 0,0001). In order to increase the statistical power of the analysis the data of both populations were combined. According to the combined data, the decrease of HbA1c after 24 weeks of treatment with evogliptin positively correlates with HbA1c level at baseline (p0.0001) and log(HOMA-B) (p=0.0042), and it negatively correlates with log(triglycerides/HDL) (p=0.0057), blood phosphorous concentration (p=0.014) and statin treatment (p=0.044). No correlation of HbA1c change at week 24 was observed with body mass index, diabetes duration and blood C-peptide concentration. Patients able to achieve HbA1c7,0 % had higher HOMA-B (53.22 36.95 и 39.67 24.74, respectively, р=0.033) and were tend to have higher HDL concentration (1.36 0.28 и 1.26 0.26 mmol/l, respectively, р=0.076) and lower triglycerides to HDL ratio (0.87 0.70 и 1.48 0.95, respectively, р=0.079). Conclusion: A patient, who benefits more when treated with evogliptin, has higher HOMA-B, lower triglycerides to HDL ratio and phosphorous concentration in the 1-2 quartiles of the normal range. Triglycerides to HDL ratio is, probably, a specific effectiveness predictor for Russian, but not for Korean subpopulation. These data prove the difference in effectiveness prediction for different drugs of DPP-4 inhibitors group and reveal the need of further investigation

Assessment the equivalence of the bioanalogue insulin lizpro biphasic 25 (Geropharm-bio, Russia) and Humalog® Mix 25 (Lilly France, France) using the euglycemic hyperinsulinum clamp method on healthy volonters

Background: Modern medicine requires use of effective antidiabetic drugs that can imitate the natural profile of insulin in the body of patients with diabetes mellitus. Examples of such preparations include biphasic insulin lispro, which is a mixture of insulin lispro ultra-short action and insulin lispro protamine suspension with prolonged effect. The clinical trials (CT) program for biosimilar insulins contains pharmacology studies: pharmacokinetics (PK), pharmacodynamics (PD) and clinical safety studies. Aims: To demonstrate Biphasic Insulin Lispro 25, suspension for subcutaneous administration, 100 U/ml (GEROPHARM-Bio, Russia) and Humalog® Mix 25, suspension for subcutaneous administration, 100 U/ml (Lilly France, France) have comparable pharmacokinetic profiles under conditions of hyperinsulinemic euglycemic clamp (HEC) in healthy volunteers. Materials and methods: The study was conducted on 48 healthy men aged between 18 to 50 years. This was a double-blind, randomized, crossover study of comparative pharmacokinetics of drugs. The investigational products (IP) were administered before the clamp in a single dose of 0.4 U/kg subcutaneously in the abdominal wall. Regular blood sampling was performed during the study. The insulin concentrations in the samples were determined using an ELISA method. The results of the determination were used to calculate the PK parameters and construct the concentration-time curves. Adjust glucose infusion rates were based on blood glucose measurements. These data were used to calculate the PD parameters. Results: Our results demonstrated that Biphasic Insulin Lispro 25 and Humalog® Mix 25 have comparable PK and PD profiles under conditions of HEC in healthy volunteers. The confidence intervals for the ratio of the geometric mean for Cins.max and AUCins.0–12 were 87.75–99.90% and 83.76–96.98% respectively, which were well within 80–125% limits for establishing comparability. Conclusions: Biphasic Insulin Lispro 25 and Humalog® Mix 25 are equivalent based on this CT applying the HEC technique in healthy volunteers

Evaluation of biosimilarity of RinGlar® (GEROPHARM LLC, Russia) and Lantus® (Sanofi-Aventis Deutschland GmbH, Germany) using the euglycemic hyperinsulinemic clamp technique in patients with type 1 diabetes: double-blind randomized clinical trial

Background: Prevention of the development of micro-and macrovascular complications in patients with diabetes melli-tus (DM) encouraged the search for insulin analogues that allow imitating, as close as possible, a normal physiological insulin secretion in healthy people. Biosimilars (bioanalogues of reference products) play an important role in the full provision with high-quality insulin medications throughout patients. The program of clinical trials of insulin bioanalogues includes pharmacology studies: pharmacokinetics (PK), pharmacodynamics (PD) and clinical safety research.Aims: To test whether RinGlar® (GEROPHARM LLC, Russia) and Lantus® (Sanofi-Aventis Deutschland GmbH, Germany) have similar PK and PD profiles in a hyperinsulinemic euglycaemic clamp (HEC) setting in patients with type 1 diabetes mellitus. Permission of the Ministry of Health of the Russian Federation No. 150 of 03/03/2016.Materials and methods: The study was conducted in 42 patients with type 1 diabetes aged 18 to 65 years. A doubleblind, randomized, crossover study of comparative PK and PD of drugs was chosen as a study design. The investigational products were injected after achieving a state of euglycemia before the HEC in a single dose of 0.6 U/kg subcutaneously into the subcutaneous fat of the anterior abdominal wall. During the study, regular blood sampling was performed, the amount of insulin glargine in the samples was determined by ELISA. The results are used to calculate the PK parameters and generate the concentration-time curves. The glucose infusion rate was corrected based on the measurement of glycemia. These data are used to calculate the PD parameters.Results: RinGlar® and Lantus® interventions have comparable PK and PD profiles in HEC setting in patients with type 1 diabetes. This is confirmed by the similarity of the main PK/PD parameters, PK/PD curves, and comparable safety. The confidence intervals of the geometric mean ratio were 81.02% - 120.62% for the PK parameter AUCins0-T, and 85.43% - 115.64% for the PD-parameter AUCGIR0_T, which fall within the specified limits of 80% - 125% to establish comparability between drugs.Conclusions: Results of the clinical trial demonstrate the biosimilarity of the products RinGlar® and Lantus®