Predictors of effectiveness of glucagon-like peptide-1 receptor agonist therapy in patients with type 2 diabetes and obesity

Background: Type 2 diabetes mellitus (DM2), which mainly develops from visceral obesity, is a socially significant disease. Reduction of losses from DM2 is a priority in modern medicine development. Glucagon-like peptide-1 receptor agonists (aGLP-1) present one of few groups of antidiabetic drugs that allows to reduce not only glycemia, but also weight in DM2. Taking into account predictors of response to the therapy will allow to reach trearment targets with the highest probability, maintaining a safety of treatment, to optimize recommendations for administration of aGPP-1 as much as possible. Aims: To assess dynamics of metabolic parameters, to identify predictors of reduction in blood glucose, body weight and other metabolic parameters on aGLP-1 therapy in patients with DM2 with body mass index (BMI) ≥35 kg/m2. Materials and methods: The study involved 33 patients (10 men, 23 women), who had been treated with aGLP-1, the observation period for 24 weeks was planned. 3 patients terminated the participation before the appointed time (1 – due to pancreatitis development 2 – due to the lack of financial opportunity to purchase the drug). So, 30 patients (10 men, 20 women) were included in the final analysis. Examination consisted of the survey, physical examination with measurement of anthropometric, clinical parameters, filling questionnaires. Data were evaluated at baseline and after 24 weeks of treatment. Results: The study found that patients who achieved weight loss ≥ 5% initially had higher BMI (p = 0.028), lower GLP-1 (p = 0.036), had lower level of ghrelin after standard breakfast test (p = 0.022). There was trend (p = 0.071) to greater decrease in BMI in patients with restrictive type of eating behavior compared to patients who had a mixed type. More pronounced decrease in glycemia was noted in patients who had higher fasting plasma glucose level at inclusion (p = 0.001). Dynamics of HbA1c was better in patients with initially higher GLP-1 (p = 0.016) and higher levels of glycemia (p = 0.001). Also, we revealed the statistically significant decrease in triglycerides level, blood pressure by end of the treatment period. Conclusions: Results indicate the different predictors for reduction in weight, glycemia and blood pressure on aGLP-1 therapy. In addition to the metabolic parameters, level of orexigenic and anorexigenic hormones and psycho-social characteristics of patients help to estimate an expected effect of aGLP-1 therapy. When being identifying, the predictors of weight loss and the predictors of carbohydrate metabolism compensation should be studied separately. Identification of response predictors is necessary to optimize indications for this group of drugs administration in DM2

Efficacy and safety of evogliptin versus sitagliptin as add on to metformin alone in a combined russian-korean population. Evo-combi trial

Background: Dipeptidyl-peptidase-4 inhibitors (iDPP-4) are pathogenically targeted drugs for diabetes mellitus type 2 (T2DM). Evogliptin is a new member of iDPP-4 class. The drug has the longest half-elimination period among the class, and its efficacy and safety as monotherapy have been already studied in placebo-controlled randomized clinical trials. Aims: To study efficacy and safety of evogliptin as compared to sitagliptin in T2DM patients with unsatisfying glycemic control with metformin monotherapy via a multinational double blind randomized controlled trial. To compare the study results in Russian and Korean subpopulations. Materials and methods: We used a combined Russian-Korean database (1:4) of EVO-COMBI trial. 281 adult T2DM patients administered metformin alone (at least 1000 mg/day) were randomized 1:1 to add on evogliptin (142 patients) or sitagliptin (139 patients) for 24 weeks once daily. The primary endpoint was change in glycated hemoglobin (HbA1c) level at Week 24 as compared to baseline. Non-inferiority was concluded if the upper limit of the 2-sided 95% confidence interval for the HbA1c difference between treatments was 0.35 %. Subgroup analysis for between-subpopulation difference in treatment effect was also conducted. Results: The mean between-group difference was 0.03 % [95 % CI: -0.14; 0.19 %], that confirms non-inferiority of evogliptin (mean HbA1c decrease -0.58 0.70 %, p0.001) to sitagliptin (mean HbA1c decrease -0.61 0.66 %, p0.001). Evogliptin and sitagliptin both tend to be more effective in South Korean subpopulation in terms of fasting plasma glucose lowering (p=0.030), however HbA1c decrease in subpopulations was comparable (p=0.657). Both drugs were well tolerated in both subpopulations. Adverse effects were associated mostly with gastrointestinal disorders, and the frequency was comparable between treatment groups (p0.05). Gastrointestinal adverse effects were registered more often in Korean patients (p=0.014). There were no severe hypoglycemia. Frequency of mild hypoglycemia was comparable between evogliptin and sitagliptin (0.7 % and 5.2 %, respectively, p=0.365). Conclusions: Evogliptin 5 mg/day is non-inferior to sitagliptin 100 mg/day in T2DM patients with unsatisfying glycemic control with metformin monotherapy. Safety profile is also comparable. Efficacy-safety profile of evogliptin is comparable in Russian and South Korean subpopulations

Transgenerational and intergenerational effects of early childhood famine exposure in the cohort of offspring of Leningrad Siege survivors

Famine exposure during early life development can affect disease risk in late-life period, yet, transmission of phenotypic features from famine-exposed individuals to the next generations has not been well characterized. The purpose of our case–control study was to investigate the association of parental starvation in the perinatal period and the period of early childhood with the phenotypic features observed in two generations of descendants of Leningrad siege survivors. We examined 54 children and 30 grandchildren of 58 besieged Leningrad residents who suffered from starvation in early childhood and prenatal age during the Second World War. Controls from the population-based national epidemiological ESSE-RF study (n = 175) were matched on sex, age and body mass index (BMI). Phenotypes of controls and descendants (both generations, children and grandchildren separately) were compared, taking into account multiple testing. Comparison of two generations descendants with corresponding control groups revealed significantly higher creatinine and lower glomerular filtration rate (GFR), both in meta-analysis and in independent analyses. The mean values of GFR for all groups were within the normal range (GFR less than 60 mL/min/1.73 m2 was recorded in 2 controls and no one in DLSS). Additionally, independent of the creatinine level, differences in the eating pattern were detected: insufficient fish and excessive red meat consumption were significantly more frequent in the children of the Leningrad siege survivors compared with controls. Blood pressure, blood lipids and glucose did not differ between the groups. Parental famine exposure in early childhood may contribute to a decrease in kidney filtration capacity and altered eating pattern in the offspring of famine-exposed individuals.</p

Case Report : Supernormal Vascular Aging in Leningrad Siege Survivors

Age-related changes in the vascular system play an important role in the biological age and lifespan of a person and maybe affected from an early age onward. One of the indicators of changes in the vascular system is arterial wall stiffness and its main measure, i.e., carotid-femoral pulse wave velocity (cfPWV). We examined arterial wall stiffness in a sample of 305 Leningrad Siege survivors to assess how hunger and stressful conditions during fetal development and early childhood affected the state of the cardiovascular system at a later age and what factors may neutralize the negative impact sustained in early childhood. Here, we presented an evaluation of two unique patients with supernormal vascular aging (SUPERNOVA) phenotype from this cohort and described the details of congruence between hereditary resistance and practiced lifestyle yielding slower biological aging rate.Peer reviewe

Data sharing: A new editorial initiative of the international committee of medical journal editors. Implications for the editors´ network

The International Committee of Medical Journal Editors (ICMJE) provides recommendations to improve the editorial standards and scientific quality of biomedical journals. These recommendations range from uniform technical requirements to more complex and elusive editorial issues including ethical aspects of the scientific process. Recently, registration of clinical trials, conflicts of interest disclosure, and new criteria for authorship -emphasizing the importance of responsibility and accountability-, have been proposed. Last year, a new editorial initiative to foster sharing of clinical trial data was launched. This review discusses this novel initiative with the aim of increasing awareness among readers, investigators, authors and editors belonging to the Editors´ Network of the European Society of Cardiolog