Individualisation of basal insulin therapy of type 2 diabetes: evidence from large randomized controlled trials

Initiation of insulin therapy with basal insulin analogues has become the standard of care for type 2 diabetes mellitus (T2DM). Timely administration of insulin allows not only to slow down the progression of type 2 diabetes, but also to reduce the frequency and severity of complications associated with it. This paper reviews the efficacy and safety of the use of the latest basal insulin analogues in type 2 diabetes from the perspective of current clinical guidelines, and also reviews updated data on the efficacy and safety of therapy by various members of the class. In this paper a review of the efficacy and safety of latest basal insulin analogues use in T2DM from the standpoint of current clinical guidelines has been carried out, and updated data on the efficacy and safety of therapy by various members of the class have been reviewed, taking into account their impact on the risk of hypoglycemia and glycemic variability. The available data indicate that insulin degludec 200 U/mL may be the drug of choice for those at high risk of developing severe forms of hypoglycemia. Since severe hypoglycemia and high glycemic variability are important risk factors for cardiovascular events and mortality, it has been shown that a differentiated approach to insulin therapy in the treatment of T2DM is currently advisable, taking into account the effect on the risk of hypoglycemia and glycemic variability

A new design for a green calcium indicator with a smaller size and a reduced number of calcium-binding sites

Genetically encoded calcium indicators (GECIs) are mainly represented by two- or one-fluorophore-based sensors. One type of two-fluorophore-based sensor, carrying Opsanus troponin C (TnC) as the Ca2+-binding moiety, has two binding sites for calcium ions, providing a linear response to calcium ions. One-fluorophore-based sensors have four Ca2+-binding sites but are better suited for in vivo experiments. Herein, we describe a novel design for a one-fluorophore-based GECI with two Ca2+-binding sites. The engineered sensor, called NTnC, uses TnC as the Ca2+-binding moiety, inserted in the mNeonGreen fluorescent protein. Monomeric NTnC has higher brightness and pH-stability in vitro compared with the standard GECI GCaMP6s. In addition, NTnC shows an inverted fluorescence response to Ca2+. Using NTnC, we have visualized Ca2+ dynamics during spontaneous activity of neuronal cultures as confirmed by control NTnC and its mutant, in which the affinity to Ca2+ is eliminated. Using whole-cell patch clamp, we have demonstrated that NTnC dynamics in neurons are similar to those of GCaMP6s and allow robust detection of single action potentials. Finally, we have used NTnC to visualize Ca2+ neuronal activity in vivo in the V1 cortical area in awake and freely moving mice using two-photon microscopy or an nVista miniaturized microscope

Фармакоэкономический анализ применения препарата цефтазидим+авибактам (Завицефта®) при лечении сепсиса, вызванного карбапенеморезистентными энтеробактериями

Aim: to assess the economic outcomes of using ceftazidime + avibactam (compared with the recommended treatments) in adult patients with sepsis caused by carbapenem-resistant enterobacteria.Methods. The economic assessment was made using the cost-effectiveness analysis and budget impact analysis. The cost-effectiveness and budget impact analyses were performed using the Microsoft Excel software.Results. The treatment efficacy analysis showed that patients treated with the fixed-dose combination ceftazidime + avibactam had fewer days spent in the ICU and higher clinical cure rates than patients receiving the reference drug combinations (8 vs 18 days and 75% vs 34.8%, respectively, p=0.031). The cost of treatment with ceftazidime + avibactam amounted to 228.3 thousand rubles, which was lower than the cost of using the alternative treatment regimens by 34.5-229.5 thousand rubles or 13.12-50.14%. According to the cost-effectiveness analysis, the use of ceftazidime + avibactam is pharmacoeconomically effective as it reduces the cost of patient clinical cure case by 61-72% (depending on the treatment regimen used); in addition, the ceftazidime + avibactam allows for managing the hospitalized patient at a cost lower by 76270 thousand rubles or 16-40% than the compared treatment. The median economic benefit from using the fixed dose combination ceftazidime + avibactam is 154 thousand rubles (28% savings compared with the current practice). The budget impact analysis showed that the reduction in the health budget burden would reach 29% or 34.3 million rubles in year. The sensitivity analysis confirmed the above results.Conclusion. Based on the obtained results, we conclude that the ceftazidime + avibactam combination in patients with sepsis caused by carbapenem-resistant bacteria is economically preferable as compared with the current antibiotic therapy regimens.Цель - провести оценку экономических последствий применения препарата цефтазидим+авибактам в сравнении с рекомендованными схемами терапии у взрослых пациентов с сепсисом, вызванным карбапенеморезистентными энтеробактериями.Материалы и методы. Оценка экономических последствий проведена с использованием анализа «затраты-эффективность » и анализа влияния на бюджет. Расчет затрат проводился в модели, разработанной в программе Microsoft Excel.Результаты. Анализ эффективности показал, что пациенты, получавшие фиксированную комбинацию цефтазидим/авибактам, характеризовались меньшим количеством дней, проведенных в отделении реанимации и интенсивной терапии (ОРИТ) и более высокими показателями клинического излечения, чем пациенты, получающие комбинации сравнения в течение 14 дней от начала лечения (8 против 18 дней и 75% против 34,8% соответственно, р=0,031). Стоимость курса цефтазидим+авибактам составила 228,3 тыс. руб., что на 34,5-229,5 тыс. руб. (13,12-50,14%) ниже расходов на альтернативные схемы лечения. По результатам анализа «затраты-эффективность» показано, что применение препарата цефтазидим+авибактам фармакоэкономически эффективно и позволяет снизить стоимость случая клинического излечения больного на 61-72% в зависимости от используемой схемы терапии, при этом характеризуясь наименьшей стоимостью ведения больного, позволяя сократить сумму прямых затрат на ведение больного на 76270 тыс. руб. (16-40%). Медиана экономической выгоды при использовании фиксированной комбинации цефтазидим+авибактам составляет 154 тыс. руб. (28% экономии в сравнении с текущей практикой). Анализ влияния на бюджет показал, что это приведет к снижению нагрузки на бюджет системы здравоохранения на 29%, или на 34,3 млн руб. в год. Анализ чувствительности подтвердил полученные результаты.Заключение. На основании комплексного фармакоэкономического исследования можно сделать вывод о том, что применение препарата цефтазидим+авибактам у пациентов с сепсисом, вызванным карбапенеморезистентными бактериями с экономической точки зрения является предпочтительной опцией по сравнению с применением текущих схем антибактериальной терапии

Анализ клинико-экономической эффективности применения бенрализумаба в сравнении со стандартной терапией у пациентов с тяжелой бронхиальной астмой

Objective: to evaluate the clinical and economic effectiveness of benralizumab in comparison with standard therapy in patients with severe bronchial asthma (SBA) with an eosinophilic phenotype in the Russian Federation.Material and methods. A clinical and economic analysis of using benralizumab in addition to standard therapy was carried out in comparison with standard therapy for SBA with an eosinophilic phenotype by means of a modeling method. Cost calculations were performed in a mathematical model adapted to the Russian healthcare conditions with the help of cost indicators and patient population characteristics.Results. The use of benralizumab as a mandatory component of standard therapy compared with standard therapy alone for SBA with an eosinophilic phenotype will allow for an additional 0.65 life years gained (LYGs) and 1.12 quality-adjusted life years (QALYs) per 1 patient during lifelong therapy. It will provide avoiding 4.95 exacerbations, simultaneously with a reduction in total costs by 584,144 rubles by reducing gross domestic product (GDP) losses due to mortality and temporary disability over an assessment horizon equal to life expectancy. The costs of 1 LYG and 1 QALY in the case of benralizumab were 869,455 and 1,252,056 rubles, in the case of standard therapy they were 911,615 and 1,303,811 rubles, respectively.Conclusion. Intensification of SBA therapy with an eosinophilic phenotype with benralizumab is clinically justified (leads to an increase in life expectancy, a decrease in the rate of exacerbations and an increase in patients’ working life), and is also economically feasible, as it allows to reduce direct costs and GDP losses of the state.Цель: оценить клинико-экономическую эффективность применения бенрализумаба в сравнении со стандартной терапией у пациентов с тяжелой бронхиальной астмой (ТБА) с эозинофильным фенотипом в Российской Федерации.Материал и методы. Проведен клинико-экономический анализ использования лекарственного препарата бенрализумаб в добавление к стандартной терапии в сравнении со стандартной терапией ТБА с эозинофильным фенотипом методом моделирования. Расчет затрат выполнен в математической модели, адаптированной к российским условиям здравоохранения с помощью стоимостных показателей и характеристик популяции пациентов.Результаты. Применение бенрализумаба в качестве обязательного компонента в составе стандартной терапии в сравнении с только стандартной терапией у пациентов с ТБА с эозинофильным фенотипом позволит дополнительно получить 0,65 добавленного года жизни (англ. life year gained, LYG) и 1,12 года жизни с поправкой на качество (англ. quality-adjusted life year, QALY) на 1 пациента при пожизненной терапии, позволив избежать 4,95 обострения, одновременно со снижением общих затрат на 584 144 руб. за счет сокращения потерь валового внутреннего продукта (ВВП) по причине смертности и временной нетрудоспособности при горизонте оценки, равном продолжительности жизни. Стоимость 1 LYG и 1 QALY в случае бенрализумаба составила 869 455 и 1 252 056 руб., в случае стандартной терапии – 911 615 и 1 303 811 руб. соответственно.Заключение. Интенсификация терапии ТБА с эозинофильным фенотипом препаратом бенрализумаб является клинически обоснованной (приводит к увеличению продолжительности жизни, снижению частоты обострений и увеличению продолжительности трудоспособного периода жизни пациентов), а также экономически целесообразной, т.к. позволяет сократить прямые затраты и потери ВВП со стороны государства

Сравнительный клинико-экономический анализ интенсификации терапии базальным инсулином или дапаглифлозином у пациентов с неконтролируемым сахарным диабетом 2-го типа

Objective. Determine if dapagliflozin use is pharmacoeconomically reasonable option for patients with inadequate glycemic control compared with basal insulin.Materials and Methods. The study was conducted according to standard pharmacoeconomic methods: cost-utility analysis (CUA), budget impact analysis (BIA).Results. The use of dapagliflozin as an alternative to basal insulin can reduce health system costs, improves the quality of life of patients, adding 0.73 QALY per patient. Modelling suggests that dapagliflozin introduction could delay the start of insulin treatment by an average of 6.5 years that in turn will allow achieving cost savings and improving the quality of life of patients.Conclusions. Dapagliflozin therapy is the preferred alternative to basal insulins, due to lower costs and improvement in the quality of life of patients.Цель – определить, является ли выбор дапаглифлозина фармакоэкономически обоснованным при включении его в терапию у пациентов с недостаточным гликемическим контролем в сравнении с базальными инсулинами.Материалы и методы. Исследование проводилось по стандартным фармакоэкономическим методикам анализа полезности затрат (CUA), оценки влияния на бюджет.Результаты. Применение дапаглифлозина в качестве альтернативного базальному инсулину препарата при интенсификации терапии СД 2-го типа позволяет сократить затраты системы здравоохранения, а также повышает качество жизни пациентов, добавляя 0,73 QALY в расчете на одного пациента и позволяет отложить старт инсулинотерапии в среднем на 6,5 лет, что позволит достичь экономии бюджетных средств и улучшить качество жизни пациентов.Выводы. Терапия дапаглифлозином является предпочтительной альтернативой в сравнении с использованием базальных инсулинов, поскольку сопровождается наименьшими затратами и позволяет улучшить качество жизни пациентов

CLINICAL AND ECONOMICAL COMPARISON OF RIVAROXABAN AND APIXABAN USE IN PATIENTS WITH NON-VALVULAR ATRIAL FIBRILLATION

Aim. To compare cost-effectiveness of the use of direct factor Xa inhibitors rivaroxaban and apixaban in patients with non-valvular atrial fibrillation (AF) and to assess the impact of the both therapies on the healthcare budget of Russian Federation.Material and methods. Pharmacoeconomic analysis with "decision tree" modeling is performed. The costs of regimens using rivaroxaban and apixaban were calculated. Assessment of the likelihood of cerebrovascular complications during anticoagulant therapy was performed, and the average additional costs in development of adverse  clinical effects were calculated. The average costs of treatment regimens used in view of the probability of occurrence of all the clinical effects,  were calculated as a result of the modeling.Results. The results of the pharmacoeconomic analysis shown, that the strategy of the use of rivaroxaban for stroke prevention in patients with non-valvular AF is less costly 49558.43 rubles for one patient per year. The strategy of apixaban application costs higher by 0.15% (50027.57 rubles). Cost reduction for the year of rivaroxaban therapy in a cohort  of 1000 patients was 469140 rubles due to decrease in the incidence of cerebrovascular complications in comparison with apixaban therapy.Conclusion. When choosing pharmacotherapy strategy to prevent the stroke in patients with non-valvular AF rivaroxaban use is more effective, than the use of apixaban, from the clinical and pharmacoeconomic points of view

Pharmacoeconomic analysis of the anidulafungin (EraxisR) in adult patients with invasive candidiasis

Objective: to assess the economic outcomes of using anidulafungin (Eraxis®) in comparison with the recommended treatment regimens in adult patients with invasive candidiasis.Materials and methods. The economic impact assessment was carried out using “cost–effectiveness” analysis and “budget impact” analysis. “Cost–effectiveness” and “budget impact” analyses were performed in Microsoft Excel model.Results. An analysis of the effectiveness showed that the use of anidulafungin is characterized by higher survival (79.25 % vs 66.17 % for caspofungin and 60.84 % for mikafungin). The cost of anidulafungin was 377.7 thousand rubles, which is comparable with the course of caspofungin and 61 % lower than the cost of micafungin therapy. “Cost–effectiveness” analysis showed that the use of the anidulafungin in the treatment of invasive candidiasis is pharmacoeconomically effective and has a “cost–effectiveness” ratio comparable to caspofungin in terms of the effectiveness of therapy for 7 days and exceeds it in terms of the cost of preserving the patient»s life by 14.5 %. Compared to micafungin, anidulafungin is both more economical and more effective in terms of preserving the patient's life, reaching an advantage of up to 45 %. An analysis of the impact on the budget showed that with the complete replacement of the currently used treatment regimens in the target population of 11,840 patients with invasive candidiasis with anidulafungin, it is possible to reduce the burden on the budget of the healthcare system to 17 % or 1458.6 million rubles in year. The average savings in the 3‑year study horizon, taking into account the gradual switching of 25, 50 and 75 % of the target patient population, amounted to 1277.9 million rubles per year or 14.4 %. A sensitivity analysis confirmed the results.Conclusion. Based on results, it can be concluded that the use of the drug anidulafungin (Eraxis®) in patients with invasive candidiasis is economically the preferred option compared to the use of current antibiotic therapy regimens

Pharmacoeconomic analysis of ceftazidime+avibactam (Zavicefta®) in the treatment of sepsis caused by carbapenem-resistant enterobacteria

Aim: to assess the economic outcomes of using ceftazidime + avibactam (compared with the recommended treatments) in adult patients with sepsis caused by carbapenem-resistant enterobacteria.Methods. The economic assessment was made using the cost-effectiveness analysis and budget impact analysis. The cost-effectiveness and budget impact analyses were performed using the Microsoft Excel software.Results. The treatment efficacy analysis showed that patients treated with the fixed-dose combination ceftazidime + avibactam had fewer days spent in the ICU and higher clinical cure rates than patients receiving the reference drug combinations (8 vs 18 days and 75% vs 34.8%, respectively, p=0.031). The cost of treatment with ceftazidime + avibactam amounted to 228.3 thousand rubles, which was lower than the cost of using the alternative treatment regimens by 34.5-229.5 thousand rubles or 13.12-50.14%. According to the cost-effectiveness analysis, the use of ceftazidime + avibactam is pharmacoeconomically effective as it reduces the cost of patient clinical cure case by 61-72% (depending on the treatment regimen used); in addition, the ceftazidime + avibactam allows for managing the hospitalized patient at a cost lower by 76270 thousand rubles or 16-40% than the compared treatment. The median economic benefit from using the fixed dose combination ceftazidime + avibactam is 154 thousand rubles (28% savings compared with the current practice). The budget impact analysis showed that the reduction in the health budget burden would reach 29% or 34.3 million rubles in year. The sensitivity analysis confirmed the above results.Conclusion. Based on the obtained results, we conclude that the ceftazidime + avibactam combination in patients with sepsis caused by carbapenem-resistant bacteria is economically preferable as compared with the current antibiotic therapy regimens