Due to the high efficiency of glucagon-like peptide-1 (GLP-1) receptor agonists therapy in only a part of patients, the search for predictors of response to the treatment is a relevant problem. Purpose. The purpose is to compare the efficacy of liraglutide and exenatide therapy in obese patients with type 2 diabetes mellitus (T2DM) and to evaluate the predictors of response to glycated hemoglobin (HbA1c), weight and lipids reduction. Material and methods. The study included 47 patients with type 2 diabetes and obesity who received GLP-1 receptor agonists therapy. 26 patients were treated with liraglutide, 21 patients were treated with exenatide. We measured the parameters of carbohydrate and lipid metabolism, the levels of hormones involved in glucose and lipids metabolism and in appetite regulation. Blood pressure was measured. These parameters were evaluated at baseline and after 24 weeks of treatment. Results. Patients receiving exenatide therapy showed a tendency towards more frequent HbA1c level reduction by 1% or more (60% versus 30.4%, p = 0.07). The effects of liraglutide and exenatide on weight and waist circumference were comparable. When assessing the predictors of response to the therapy, a more pronounced decrease in HbA1c level (by 1% or more) was in the patients with a higher initial HbA1c level (8.7 (8.2; 9.7) versus 8.2 (6.9; 8.7)%, p = 0.04), as well as with a higher initial GLP-1 level (0.12 (0.05; 0.17) versus 0.040 (0.01; 0.09) ng/ml.) A more significant decrease in the triglycerides (TG) level was detected in patients with a higher level of glucose-dependent insulinotropic peptide (GIP) before therapy (409 (316.0; 431.4) pg/ml in patients who reduced TG level by 30% or more and 331.5 (324.9; 367.1) pg/ml in patients with a lower decrease in TG level). Among the studied parameters, no predictors of body mass reduction were revealed. Conclusion. Measurement of HbA1c, GLP-1, GIP level may be useful to predict the efficacy of GLP-1 receptor agonists therapy.

Type 2 diabetes mellitus (T2DM) is a progressive disease accompanied by a gradual worsening of β-cell function. With a long course of T2DM, a significant proportion of patients develop absolute insulinopenia and there is a need to transfer the patient from oral hypoglycemic drugs (OHD) to basal insulin therapy in combination with OHD or to the basal-bolus regimen of insulin therapy (IT). More than 80% of patients with T2DM are obese or overweight and the addition of insulin, which is a lipogenetic hormone, to the therapy contributes to even greater weight gain, which serves as a prerequisite for increasing cardiovascular risks, as well as the appearance and progression of biomechanical problems such as arthrosis of the joints, venous insufficiency. In this review article, we will consider and evaluate the benefits of administering combinations of basal insulin glargine in combination with glucagonlike peptide-1 receptor agonists (GLP-1ra) lixisenatide to one of the most rational treatment regimens for patients with T2DM insulin deficiency and persistent insulin resistance. Also, the article focuses on the variability of glycemia, which according to research can play an important role in the pathogenesis of atherosclerosis and can be an independent risk factor for cardiovascular complications in patients with diabetes. Due to the fact that glycemic control is based on the determination of predominantly glycated hemoglobin (HbA1c) as a measure of average glucose concentration, it is known that this marker does not accurately reflect glycemic variability, which is characterized by the amplitude, frequency and duration of hypo- and hyperglycemic fluctuations. A fixed combination of insulin preparations glargin 100 and GLP-1ra lixisenatide allows to select individually effective dosage for a patient with type 2 diabetes and obesity, will help to achieve several goals at the same time - from improving glycemic parameters without increasing body weight and without increasing the risk of hypoglycemia, to significantly reduce the need for insulin with its previous use, as well as reduce the risk of cardiovascular complications.

Objective. Comparison of the effects of liraglutide and dulaglutide on the dynamics of scales and markers of hepatic fibrosis.Materials and methods. 35 patients with NAFLD were included in the study and received liraglutide 1.8 mg or dulaglutide 1.5 mg once daily for 6 months.Results. Body weight and glycated hemoglobin (HbA1C) decreased significantly and comparable after 6 months of treatment in both groups. Serum aspartate aminotransferase (AST) levels decreased only in the dulaglutide group. The decrease in the AST level in the dulaglutide group was from 31.9 ± 26.8 to 30.8 ± 10.6 U / L (p = 0.04). The dynamics of the risk of fibrosis reached statistical significance only when assessed on the FIB-4 scale in the liraglutide group when comparing the baseline values and values after 6 months of treatment — 1.18 ± 0.51 and 0.97 ± 0.40, respectively (p = 0.022). In the dulaglutide group, there was also an insignificant positive dynamics of 1.31 ± 0.53 and 1.11 ± 0.23 (p = 0.865), which can be explained by the minimal severity of changes at baseline.Conclusions. The study demonstrated comparable effects of liraglutide and dulaglutide on metabolic parameters and, at the same time, the advantage of liraglutide in influencing the dynamics of the risk of fibrosis, assessed on the FIB-4 scale. To unequivocally confirm the benefits of liraglutide in the treatment of patients with NAFLD, randomized prospective comparative studies of various aGPP1 on large samples of patients with different stages of NAFLD are needed.