Prediction of early response to liraglutide therapy in patients with obesity

BACKGROUND: The main goal of treating obesity is to reduce the risk of developing its complications and comorbid diseases, which requires a steady decrease in body weight by at least 5–10%. In Russia in 2016, the list of drugs for the treatment of obesity was supplemented by a glucagon-like peptide 1 receptor agonist (GLP-1) – liraglutide . There is evidence that about one third of patients do not achieve a clinically significant decrease in body weight during treatment with liraglutide, while the factors that predict the so-called early response to treatment are currently unknown. AIM: To identify prognostic factors of an early response to complex therapy of exogenously constitutional obesity, including agonist of GLP-1 receptors liraglutide, and to evaluate the effect of this therapy on the dynamics of levels of endogenous peptide bioregulators of eating behavior (IB). MATERIALS AND METHODS: The study included 42 patients with exogenously constitutional obesity, which were divided into 2 groups, comparable by sex, age and body mass index (BMI). The first group (n=22) received treatment recommendations for the correction of nutrition and physical activity, as well as liraglutide 3.0 mg for 3 months. The second group (n=20) received only recommendations for the correction of nutrition and physical activity. At the start and after 3 months, anthropometric characteristics and laboratory parameters were evaluated in all patients, including the levels of endogenous peptide bioregulators of IB (leptin, ghrelin, obestatin and GLP-1), their dynamics was compared between groups. Depending on the therapeutic effect, the 1st group was divided into two subgroups: those who achieved (n = 14) and did not achieve (n = 8) a clinically significant decrease in body weight. In both subgroups, baseline characteristics were analyzed as possible prognostic factors for the effectiveness of complex therapy. RESULTS: To predict an early response to complex therapy, including liraglutide, a mathematical model has been developed that is implemented as a calculator in MS Excel and contains a combination of initial body weight and fasting plasma ghrelin. The dynamics of body weight and BMI in the group of complex therapy was statistically significantly higher than that in the group of isolated lifestyle modifications (ILM). CONCLUSIONS: The proportion of individuals with an early response to 3.0 mg liraglutide therapy is comparable to that of data from randomized clinical trials. The mathematical model, which includes a combination of initial body weight and plasma ghrelin, allows predicting the likelihood of a clinically significant decrease in body weight after 3 months of using liraglutide 3.0 mg in combination with ILM with a sensitivity of 86% [65%; 97%] and prognostic value of a positive result of 80% [60%; 95%]

Obesity and stress: endocrine and social aspects of the problem in the modern Russian society

The purpose of the article is to consider stress as one of the etiological factors of obesity and metabolic syndrome. The review discusses both endocrine and social aspects of stress as a syndrome of adaptation to the current situation in Russian society. It is emphasized that lifestyle factors contributing to the growth of overweight are gaining popularity in the society, and the high incidence of obesity is directly related to the level, quality and lifestyle of a modern man. Constant nervous tension, negative emotions, fear in conditions of abundance of food directly contributes to obesity, which is associated with a large number of other serious diseases. Chronic hyperactivation of the hypothalamic-pituitary-adrenal axis and chronic hypersecretion of cortisol, if persistence is not a purely physiological condition. Endocrine mechanisms mediating the development of metabolic disorders on the background of chronic stress include activation of the hypothalamic-pituitary-adrenal system, changes in eating behavior, hyper-production of glucagon and triglyceride accumulation in visceral fat depots. Processes and social changes occurring in modern society contribute to the construction of everyday socio-cultural environment characterized by increased stress. Chronic stress in combination with physical inactivity, the result of improper lifestyle of modern people, becomes an effective factor contributing to the spread among the population of Russia not only overweight, but also various forms of obesity. It is emphasized that at the state level there is an urgent need to adopt and implement effective programs and mechanisms to ensure the population meets modern requirements and environmental standards of healthy food, rationalization of food distribution among the population, the formation of a culture of food consumption, improving the quality of life of the population and the culture of a healthy lifestyle, teaching the population the correct stress-coping behavior

Navigated repetitive transcranial magnetic stimulation to correct eating behavior in obesity (clinical cases)

Obesity is a pathological condition caused by overweight and requiring medical intervention. The clinical and scientific experience gained over the past decades has allowed researchers to consider this problem as an independent disease with its own pathophysiological features, prevalence, incidence, approaches to therapy and prevention. One of the most important factors in the pathogenesis of obesity is disordered eating behavior, the central regulation of which is carried out with the active participation of the prefrontal cortex. Impact on this area (for example, using non-invasive brain stimulation) may be one of the promising ways to modulate eating behavior. The article describes clinical cases of treatment of morbid obesity using navigated rhythmic transcranial magnetic stimulation (rTMS). Different patterns of dorsolateral prefrontal cortex (DLPFC) activation before and after rTMS are demonstrated. Possible mechanisms of the influence of DLPFC on the formation of eating behavior are also considered. These data underline the important role of DLPFC dysregulation in obesity, as well as show potentially effective neuromodulation techniques

The place of central-acting drugs in the algorithms of treatment of primary obesity

Pharmacotherapy is an essential component of obesity treatment, as well as efforts focused on changing the lifestyle, correcting the food consumption and increasing the physical activity. The administration of central-acting drugs as pharmacotherapy of obesity is pathogenetically justified and allows improving the effectiveness of treatment. In this article, the use of sibutramine, a serotonin and norepinephrine reuptake inhibitor, is considered in various aspects of endocrinologist’s practice. In addition to aforesaid there is an application of a specific clinical observation

The role of neurotransmitters in regulation of energy homeostasis and possibility of drug correction of its disturbances in obesity

In today's world the problem of obesity is discussed in the context of non-communicable diseases, leading to significant encumbrances on society. This article provides information about the basics of the regulation of energy balance and eating behavior. Particular attention is paid to the role of neurotransmitters, including serotonin, a metabolic disorder that is one of the suspected causes of eating disorders. Demonstrated experience in the use of sibutramine in the world, and in the Russian practice, taking into account the impact on the development of comorbid conditions and their complications

The role of neurotransmitters in regulation of energy homeostasis and possibility of drug correction of its disturbances in obesity

In today's world the problem of obesity is discussed in the context of non-communicable diseases, leading to significant encumbrances on society. This article provides information about the basics of the regulation of energy balance and eating behavior. Particular attention is paid to the role of neurotransmitters, including serotonin, a metabolic disorder that is one of the suspected causes of eating disorders. Demonstrated experience in the use of sibutramine in the world, and in the Russian practice, taking into account the impact on the development of comorbid conditions and their complications

Modern concepts of the pathogenesis of obesity and new approaches to its correction

The present review considers modern concepts of the physiological mechanisms of the formation of food behavior in a norm at several levels, beginning with the cellular level and ending with the level of functional systems. Neuroimaging methods used for both the study of the pathophysiological foundations of eating disorders and for determining the target for neurostimulation techniques are described. Methods of non-invasive brain stimulation such as transcranial magnetic stimulation and transcranial electrical stimulation, the mechanisms of their influence and aspects of safety of application are reviewed, the latest data on the results of studies on the use of the above methods in the therapy of obesity are summarized