Evaluation of immunogenicity, efficacy and safety of GP40041 compared to Humulin® NPH in patients with type 2 diabetes mellitus

Background. GP40041 is a biosimilar to Humulin® NPH. GP40041 is registered and administrated in Russia since 2004. However, due to changes in the regulatory requirements for biosimilar insulin development programme, we have conducted additional clinical trials of GP40041 including a comparative clinical trial of immunogenicity of biosimilar GP40041 and reference drug Humulin® NPH. Aims. To demonstrate a non-inferior immunogenicity, and comparable safety and effi cacy of GP40041compared to Humulin® NPH. Materials and methods. 201 patients with T2DM were recruited at 14 centers. We randomly assigned patients 1:1 to receive Humulin® NPH (98 patients, the active control group) or GP40041 (103 patients). The trial included 2 parallel groups of T2DM patients, who received insulin for 28 weeks: 4 weeks of titration period and 24 weeks of treatment period. The primary endpoint was the anti-insulin antibody concentration and its change at Week 12 and 24 as compared to baseline. The secondary endpoint was change in glycated hemoglobin (HbA1c) level, insulin daily dose and fasting plasma glucose (FPG) concentrations at Week 24 as compared to baseline. Results. There was no statistically signifi cant diff erence in terms of immunogenicity endpoints between GP40041 and Humulin® NPH groups. There was no diff erence in the change of HbA1c level and insulin dose aft er treatment between both groups. Both drugs were well tolerated. Adverse eff ects were comparable between treatment groups. All hypoglycemic episodes were light and the most of the episodes were registered during daytime. Frequency of hypoglycemic episodes was comparable between GP40041 and Humulin® NPH groups. Conclusions. GP40041 is comparable to Humulin® NPH in T2DM patients in terms of immunogenicity, safety and efficacy

Patient education: interpretation of medical terms as a key part of diabetes mellitus treatment

Background: Only a little percent of chronically ill patients was found to follow physicians’ prescriptions. One of the reasons for this issue is misunderstanding of recommendations due to inappropriate interpretation of medical terms, contained in medical advice. Aims: The study is aimed to evaluate the quality of patient interpretation of the most frequently used medical terms in diabetes mellitus field (DM) and to evaluate the impact of misunderstanding on diabetes control. Materials and methods: 13 endocrinologists composed 2 lists of the most frequently used terms – one list for DM type 1 and one for DM type 2. We selected 10 terms for DM type 1 and 10 terms for DM type 2, mentioned by the most of participated doctors, and created 2 kinds of questionnaire for patients. Patients were to explain the terms in written if they were aware of terms’ meaning. Three independent researchers evaluated every answer according to a 0 to 10 scale, where 0 was for totally incorrect or no answer, and 10 was for a completely correct answer. Patients also filled in the forms about their social and demographic parameters. Statistical analysis was conducted with the use of Wilcoxon Test and linear regression model. Results: 89 patients with DM type 1 (27% men, HbA1c (mean±SD) 7,95±1,77%) and 86 patients with DM type 2 (27% men, HbA1c (mean±SD) 8,11±1,91%) were included into the study. Patients with type 1 DM received a greater overall score for understanding the terms than those with type 2 DM (p <0.0001) – 57.84±22.66 and 39.33±22.02 from 100, respectively. 38 (42.7%) participants with DM type 1 reported that they know all 10 terms, but only 15 (16.8%) respondents understand terms correctly. In the group of type 2 DM patients 9 (10.5%) of all answered yes for all the terms, but really know terms only 2 (2.3%) participants. In both groups, the total score of the terms knowledge did not correlate with the HbA1c level (р=0.698 and р=0.319 for type 1 and type 2 DM groups, respectively). Conclusion: The most of patients with DM do not understand relevant medical terms properly. Some patients are in the wrong belief that they have no misunderstandings with their consulting doctors. However, terms understanding does not influence on glycemic control (HbA1c level). During the medical consultation, endocrinologists should check if a patient understands their advice properly to improve understanding and compliance of patients

Efficacy and Safety of Lacosamide in Painful Diabetic Neuropathy

OBJECTIVE: To evaluate efficacy and safety of lacosamide compared with placebo in painful diabetic polyneuropathy. RESEARCH DESIGN AND METHODS: Diabetic patients with at least moderate neuropathic pain were randomized to placebo or lacosamide 400 (in a slow or standard titration) or 600 mg/day over 6-week titration and 12-week maintenance periods. Primary efficacy criterion was intra-individual change in average daily Numeric Pain Rating Scale score from baseline to the last 4 weeks. RESULTS: For the primary end point, pain reduction was numerically but not statistically greater with lacosamide compared with placebo (400 mg/day, P = 0.12; 600 mg/day, P = 0.18). Both doses were significantly more effective compared with placebo over the titration (P = 0.03, P = 0.006), maintenance (P = 0.01, P = 0.005), and entire treatment periods (P = 0.03, P = 0.02). Safety profiles between titration schemes were similar. CONCLUSIONS: Lacosamide reduced neuropathic pain and was well tolerated in diabetic patients, but the primary efficacy criterion was not met, possibly due to an increased placebo response over the last 4 weeks.status: publishe

Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications

Superparamagnetic iron oxide nanoparticles can providemultiple benefits for biomedical applications in aqueous environments such asmagnetic separation or magnetic resonance imaging. To increase the colloidal stability and allow subsequent reactions, the introduction of hydrophilic functional groups onto the particles’ surface is essential. During this process, the original coating is exchanged by preferably covalently bonded ligands such as trialkoxysilanes. The duration of the silane exchange reaction, which commonly takes more than 24 h, is an important drawback for this approach. In this paper, we present a novel method, which introduces ultrasonication as an energy source to dramatically accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove the generic character, different functional groups were introduced on the surface including polyethylene glycol chains, carboxylic acid, amine, and thiol groups. Their colloidal stability in various aqueous buffer solutions as well as human plasma and serum was investigated to allow implementation in biomedical and sensing applications.status: publishe

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Antimicrobial and antifungal activities of terpene-derived palladium complexes

In an era of multidrug-resistant bacterial infections overshadowed by a lack of innovation in the antimicrobial drug development pipeline, there has been a resurgence in multidisciplinary approaches aimed at tackling this global health problem. One such approach is to use metal complexes as a framework for new antimicrobials. Indeed, in this context, bismuth-, silver- and gold-derived compounds in particular have displayed demonstrable antimicrobial activity. In this work, we discuss the antimicrobial and antifungal activities of terpene-derived chiral palladium complexes against , , , , , , and . It was established that all studied coordination compounds of palladium were highly active antifungal drugs. In contrast, the subset of palladacycles possessing a palladium-carbon bond were only active against the Gram-positive bacterium . All compounds were inactive against the Gram-negative bacteria tested

Programma obespecheniya ortopedicheskoy obuv'yu bol'nykh sakharnym diabetom v Sankt-Peterburge

Цель. Анализ ближайших результатов обеспечения ортопедической обувью больных СД, находящихся под наблюдением кабинетов диабетическая стопа? двух Городских диабетологических центров (1999-2001). Материалы и методы. Проанализированы исходы у 207 больных СД, получивших направления в кабинетах диабетическая стопа? и впоследствии наблюдавшихся в них, которым было выдано 227 пар обуви (часть пациентов получила по две пары). Тяжесть диабетической полинейропатии оценивалась тестированием 10-гр. монофиламентом. Наличие ангиопатии нижних конечностей подтверждалось отсутствием пульса хотя бы на одной из артерий стоп вне зависимости от симптомов перемежающейся хромоты. Основным критерием эффективности обеспечения ортопедической обувью при краткосрочном наблюдении (6-12 мес.) были выбраны частота ношения этой обуви, частота развития повреждений вследствие ношения ортообуви. Результаты. Из 227 пар обуви больные не носили 83 пары (36,6%). Достоверных различий между пациентами, носящими и не носящими ортообувь, по основным клиническим параметрам (возраст, длительность диабета, частота нейропатии и ангиопатии) выявлено не было. Не выявлено и достоверных различий в ношении ортообуви у больных с высоким (язва стопы/ампутация в анамнезе, нейропатия, ангиопатия, деформации стоп) и низким риском (без этих факторов) развития язвы стопы/ампутации. Анализ причин отказа от ношения уже полученной обуви показал, что основными проблемами были несоответствие формы и размера особенностям стопы пациента (35 случаев), неудобство при ходьбе, вызванное неудачными конструктивными особенностями обуви (14 пациентов), слишком жесткий верхний край обуви (голенище) ? 12 больных. Выводы. Полученные данные свидетельствуют о том, что система обеспечения орто-обувью больных сахарным диабетом, особенно имеющих высокий риск развития язв/ампутаций, нуждается в изменении