Results of a clinical trial of the efficacy and safety of vildagliptin and metformin fixed combination in real clinical practice in Russia (MASTER study)

BACKGRAUND: The widespread prevalence of type 2 diabetes mellitus (T2DM), high mortality and disability of such patients are the reason for the constant active search for effective approaches to hypoglycemic therapy. Recent years have been marked by a change in the strategy for treatment initiation of T2DM. In clinical studies, evidence has been obtained about the benefits of prescribing combination therapy from the time of diagnosis. It seems important to study this treatment option also in real clinical practice.AIMS: To evaluate the effectiveness and safety of the initiation with Galvus Met® as compared with any other combination therapy approaches used in everyday clinical practice.MATERIALS AND METHODS: multicenter prospective observational study in 15 regions of Russia lasting 6 months. Patients were included in the study after the endocrinologist made a decision on the appointment of therapy. Of the men and women over 18 years of age with first diagnosed or previously untreated type 2 diabetes and a level of glycated hemoglobin >7.5%, two groups were formed. The first group included patients who received vildagliptin + metformin (Galvus Met®) in a fixed dose of 50/1000 mg, n=729, the second — another double combination (with the exception of insulin and GLP-1), n=669. The primary endpoint was defined as the proportion of patients (%) who achieved the level of HbA1c <7.0% without proven hypoglycemia at the end of the observation. The NHPQ questionnaire was used to assess the frequency of hypoglycemia.RESULTS: 1385 patients completed the study. For the other combination therapy group, metformin and sulfonylurea derivatives were most often selected (66.5%). In the Galvus Met® group, 68.7% of patients achieved an HbA1c level of <7.0% without proven hypoglycemia, which is significantly better compared to the group of other combinations (40.7%, p <0.001). Galvus Met® therapy contributed to a significantly greater decrease in HbA1c levels by the end of the study compared to other combinations (delta HbA1c -1.6 ± 0.8% versus -1.4 ± 0.9%, p <0.001). In the same group, the average level of HbA1c reached 6.7 ± 0.6% by the end of the study versus 7.1 ± 0.8% in the comparison group, p <0.001. In the Galvus Met® group, body weight decreased by 3.2 ± 3.9 kg, and in the comparison group by 1.3 ± 4.8 kg, p <0.001. The frequency of hypoglycemia episodes in the Galvus Met® group by the end of the study was significantly lower than in the comparison group: 0.8 ± 0.7 episodes per person, versus 1.4 ± 0.8, p = 0.037. In the Galvus Met® group, there were significantly fewer adverse events (4.9% versus 17.7%, p <0.001).CONCLUSIONS: In real clinical practice, Galvus Met® starting therapy has shown better efficacy and safety in terms of achieving glycemic control, HbA1c dynamics, effects on body weight, the frequency of hypoglycemic conditions compared with other combined oral hypoglycemic therapy

Cause-and-effect relationship between thyroid and liver diseases

Thyroid gland (TG) and the liver are in a complex relationship in both physiological and pathological conditions. Thyroid hormones accelerate metabolic processes, intensify the synthesis of proteins and vitamins, play an important role in the development and differentiation of all cells, including hepatocytes. In addition to the central role in the deiodination of thyroid hormones with the formation of their more active and inactivated forms, the liver also carries out their transport. Dysfunction of TG can lead to changes in liver function, and in liver diseases, abnormalities in the metabolism of thyroid hormones can occur. Most often, liver pathology in diseases of TG is manifested by an increase in the serum activity of enzymes of cytolysis and/or cholestasis. Changes in liver function tests are often observed in patients with thyrotoxicosis. They are based on oxidative stress or cholestasis. The increased activity of osteoblasts in hyperthyroidism leads to an increase in the bone fraction of alkaline phosphatase, which must be taken into account in the differential diagnosis. Hepatotoxicity of thyreostatic drugs is relatively common, ranging from minimal hepatocellular damage to fulminant liver failure. In the case of hypothyroidism, the pathophysiological mechanisms are mainly represented by lipid metabolism disorders leading to fatty degeneration. It should be remembered that severe hypothyroidism can be manifested by hyperammonemia and edematous-ascitic syndrome, requiring differential diagnosis with liver failure. Treatment of liver pathology in TG diseases includes normalization of thyroid status, and in cases of drug hepatitis – temporary withdrawal of a potentially hepatotoxic drug. The data on the association of hypothyroidism and non-alcoholic fatty liver disease in the aspect of developing new therapies are very interesting

The respiratory exercise significance in the olfaction restoration in the postcovid period

One of the pathognomonic COVID‑19 signs, occurring in 85‑98% of patients, is olfactory dysfunction, developing in the absence of pronounced inflammation and edema of the nasal mucosa. A promising medicine direction that helps restore microcirculation, increase blood oxygenation, improve metabolism and regenerate olfactory epithelial cells is the Nadi Shodhana breathing exercise technique.Objective: To assess the possibilities of using the pranayama technique as a method of restorative olfactory treatment in the post‑covid period.Materials and methods: 79 persons aged 22 to 68 years with olfactory disturbances occurring at COVID‑19 and persisting in the post‑covid period were examined. As a restorative treatment for olfactory disorders, the patients of the main group were offered a course of Nadi Shodhana breathing exercises, which is an alternate nostril breathing. Breathing training consisted of three such cycles performed three times a day at the same time for 15 days. The possibility of using the pranayama technique was assessed according to the visual analog scale. The control group consisted of 74 patients with olfactory disorders after COVID‑19 comparable in sex and age with the main group.Results: Olfactory disorders are characteristic of post‑COVID patients. Using Nadi Shodhana breathing exercise course can significantly reduce the olfactory dysfunction level in this patient category. It was showen that the pranayama technique is more effective in people under 40 years of age. It was also established that the olfaction restoration largely depends on the duration of the dysfunction period.Conclusion: The study results make it possible to recommend the using breathing exercises in patients underwent COVID‑19 to restore olfaction in the post‑COVID period

Growth hormone deficiency in childhood brain tumors and acute lymphoblastic leukemia survivors

Thanks to modern treatment protocols, childhood cancer survivors (CCS) are a very fast-growing population nowadays. Cancer therapy inevitably leads to different late adverse effects, where endocrine disorders are highly prevalent, including growth hormone deficiency (GHD) which is the most common endocrine outcome after cancer treatment in childhood and contributes to impaired growth. Short stature is a big issue, which leads to problems in psychological and social adaptation of patients and reduces their quality of life. Impact of GH treatment on various physiological processes and global outcome of CCS is of great interest. Several studies have demonstrated an influence of GH and IGF-1 on the development/tumour growth, cell proliferation. In this regard, the issue of increasing the risk of cancer recurrence and/or the development of secondary neoplasms in CCS, causes a lot of controversy and is the subject of continuous evaluation. In this review, we went through the available data on the prevalence and pathogenesis of GHD following chemo- and radiotherapy, in particular after treatment of brain tumors and acute lymphoblastic leukaemia in childhood. In addition, here we discuss the existing problems in the diagnosis of GHD, the safety of GH replacement therapy, as well as the treatment algorithm of the GHD in adults

Resolution on the results of the first working meeting of the scientific advisory board «Actual problems of glycemic variability as a new criterion of glycemic control and safety of diabetes therapy»

The Scientific Advisory Board, chaired by Professor G. R. Galstyan (cochair - A.V. Zilov), met in Moscow on 19 June 2018 to discuss the possibilities of improving the results of diabetes mellitus (DM) treatment by considering glycaemic variability (GV) as an additional criterion for effective glycaemic control (especially in patients receiving insulin therapy) and as one of the goals of treatment in patients with unstable glycaemia. The purpose of the working meeting was to develop a strategy for the introduction of GV as a predictor and as an additional criterion for assessing the effectiveness and safety of hypoglycaemic therapy to improve the pharmacotherapy of diabetes and reduce cardiovascular and total mortality. The aims of the working meeting were to conduct a comprehensive data analysis of the relationship between GV and hypoglycaemia; to gather and analyse published data and the experience of decrease in GV and improved outcomes of diabetes against the background of different types of insulin therapy; to compare existing methods of glycaemia monitoring and GV assessment and examine their validity and availability in real practice in the context of limited budget and to analyse the informativeness and clinical and prognostic significance of various parameters of GV assessment and to determine their reasonable ‘minimum’ for a comprehensive assessment of GV as a criterion for evaluating the effectiveness of DM treatment and the predictors of negative diabetes outcomes. The following reports were presented during the discussion: ‘Glycemic variability: clinical and prognostic value. Types of glycemic variability’ (Candidate of Medical Sciences, assistant Professor Zilov A.V.); ‘Methods of assessment of variability of glycemia in clinical trials and routine practice’ (PhD, Professor Markova T. N.); ‘Current international and national recommendations on glycemic monitoring’ (PhD, Professor Galstyan G. R.) and ‘Peculiarities of glycemic variability and its evaluation among children and adolescents’ (Candidate of Medical Sciences Vitebskaya A.V.)

What are new opportunities for clinical practice the VERIFY study opens and which values for native diabetes patients? Joint conclusion on the advisory board results. November 6, 2019

According to key diabetic studies, the early use of metformin glucose lowering therapy is associated with a reduced risk of developing micro- and, in the long term, 10-year follow-up, macrovascular complications and cardiovascular mortality. Short-term studies results on combined glucose lowering therapy with metformin suggests that combination therapy can have several advantages on the one side from the effectiveness of glycemic control and on another side from positive effect on the development of complications of type 2 diabetes. The question of the start time of combined hypoglycemic therapy remains open. According to the results of recent large-scale studies, real world evidence data, careful glycemic control during the first year from the moment of diagnosis of type 2 diabetes is crucial for further management of the disease and slow the progression of complications. However, due to the fact that the clinical benefits of early combination therapy were not demonstrated in randomized clinical trials, this approach, despite the theoretical background, was not recommended for widespread use in international guidelines for the treatment diabetes patients. Russian algorithms on the treatment diabetes patients recommend combined glucose lowering therapy at the start of treatment at a HbA1c level of 1% higher than the target. A 5-year VERIFY study results were demonstrated long-term sustained glycemic control in combination with vildagliptin + metformin prescribed for native diabetes patients with relatively low HbA1c values, as well as the advantages of this approach in comparison with the standard strategy for phased intensification of monotherapy. The results of the VERIFY study provided a wealth of information to discuss early treatment intensification, the clinical benefits of this approach and a possible review of the treatment strategy for native diabetes patients

The advisory board resolution on the use of sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists in type 2 diabetes

Type 2 diabetes is characterized by increasing incidence and prevalence all-over the world. Current therapeutic management of type 2 diabetes is complex and is based not only on glycemic control, but also on cardiovascular and renal risks reduction. In previous years the use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RA) increased in Russian Federation. Some manufacturers of the most widely used GLP-1 RA reported the supply decline in several countries. On Advisory board with participation of the Russian Endocrinology Association members the topics of SGLT2i and GLP-1 RA use in type 2 diabetes were discussed. The experts made conclusion that the decrease in access to GLP-1 RA does not pose serious risk for treatment of type 2 diabetes patients. SGLT2i show benefits in risk reduction of HF and CKD progression compering to GLP-1 RA, and in general show comparable efficacy in risk reduction of ACVD outcomes.  SGLT2i show less glycemic efficacy in comparison with GLP-1 RA, and their replacement may need adding antidiabetic agents from other groups

Распространенность и факторы риска развития диабетической полиневропатии у стационарных больных сахарным диабетом 1-го типа

The NISLL scale and 7 electrophysiological tests were used to diagnose distal symmetric sensorimotor polyneuropathy in 120 inpatients with type 1 diabetes mellitus. The high rate (68.3%) of symptomatic or subclinical polyneuropathy was found. The duration of metabolic disturbances rather than short-term fluctuations in glycemia in terms of HbA1c levels was shown to mainly affect the degree of polyneuropathy in the patients of this group. The additional risk factors of polyneuropathy were retinopathy, smoking or hyperlipidemia.У лечившихся в стационаре больных сахарным диабетом 1-го типа (n = 120) проведена диагностика дистальной симметричной сенсорно-моторной полиневропатии с использованием шкалы NISLL и 7 электрофизиологических тестов. Выявлена высокая частота симптомной или субклинической полиневропатии (68,3 %). Показано, что основное влияние на выраженность полиневропатии у больных данной группы оказывает длительность нарушений метаболизма, но не кратковременные колебания гликемии по показателю HbA1c. Дополнительными факторами риска развития полиневропатии являлись наличие ретинопатии, курениеи гиперлипидемия

Liver Damage in Type 1 Diabetes Mellitus

Aim. An up-to-date review of the prevalence, pathogenesis, diagnosis and management of hepatological complications of type 1 diabetes mellitus (T1D).Key points. Diabetes type 1 causes a markedly more common liver injury than traditionally assumed. Three types of hepatic damage have been described to date in T1D patients, steatosis, glycogen hepatopathy and diabetic hepatosclerosis, with the latter two apparently pathognomonic of this diabetes type. Their pathogenesis is complex and not fully understood. Its important link is a likely inherited non-physiological insulin supply to the tissue, especially at marked glycaemic fluctuations. An adequate glycaemic control is the main prevention and treatment measure in these conditions. The practitioner’s understanding of liver damage in T1D is an earnest to avoid unnecessary tests and ineffective medications.Conclusion. Both endocrinologists and internists ought to contemplate the possibility of liver involvement in T1D for improving the patient outcomes

Liver Damage in Type 1 Diabetes Mellitus

Aim. An up-to-date review of the prevalence, pathogenesis, diagnosis and management of hepatological complications of type 1 diabetes mellitus (T1D).Key points. Diabetes type 1 causes a markedly more common liver injury than traditionally assumed. Three types of hepatic damage have been described to date in T1D patients, steatosis, glycogen hepatopathy and diabetic hepatosclerosis, with the latter two apparently pathognomonic of this diabetes type. Their pathogenesis is complex and not fully understood. Its important link is a likely inherited non-physiological insulin supply to the tissue, especially at marked glycaemic fluctuations. An adequate glycaemic control is the main prevention and treatment measure in these conditions. The practitioner’s understanding of liver damage in T1D is an earnest to avoid unnecessary tests and ineffective medications.Conclusion. Both endocrinologists and internists ought to contemplate the possibility of liver involvement in T1D for improving the patient outcomes