Study of the clinical effect of dapagliflozin on metabolic indices in type 2 diabetic patients with different obesity phenotypes

Background. The study of molecular mechanisms of meta­bolic disorders in type 2 diabetes mellitus (T2DM) is an actual problem of modern endocrinology. Today, sodium-dependent glucose cotransporter-2 inhibitors (SGLT2i) are used in the therapy of T2DM, which contribute to a decrease in the degree of obesity and exhibit cardiovasoprotective properties. The aim of the study was to evaluate the effects of dapagliflozin therapy in T2DM patients on the morpho-metabolic parameters depending on the obesity phenotype. Materials and methods. One hundred and sixty-five patients with T2DM (71 women and 94 men) aged 32–82 years were examined, their glycated hemoglobin (HbA1c) level was ≥ 6.5 %. Patients were prescribed dapagliflozin (10 mg/day) and were moni­tored for 12 months. The phenotype of patients determined by the degree of general obesity (non-obese: body mass index < 30 kg/m2, obese: body mass index ≥ 30 kg/m2). Body composition indices were determined by the bioelectrical impedance method: total body fat content (%), visceral fat level (VF, from 1 to 59 units). HbA1c (%), insulin, dehydroepiandrosterone sulfate (DHEA-S)/cortisol ratio were determined; the degree of insulin resistance (HOMA-IR), visceral obesity index (VAI) were calculated. Results. The follo­wing groups of patients created: first — non-obese (n = 72); se­cond — obese (n = 93). Within each group, subgroups with normal (< 12 units) or increased VF level (≥ 12 units) were identified. After 12 months of dapagliflozin therapy, all groups of patients reported a significant decrease in glycemia; a trend or significant decrease in HbA1c; a decrease in the percentage of fat content and a decrease in VAI, which corresponds to an improvement in the functional state of adipose tissue. In patients with general and/or visceral obesity, a decrease in body mass index, percentage of total and visceral fat was detected together with an improvement in the characteristics of lipid and carbohydrate metabolism. In subgroup 2.2, the level of insulinemia significantly decreased, while in all subgroups of patients (except 1.1), the HOMA-IR index decreased. Between the groups of patients with a non-obese and obese phenotype, a significant diffe­rence in the clinical effect of long-term SGLT2i therapy on cortisol and DHEA-s levels were found, regardless of the level of VF. A significant or moderate clinical effect was found on the change in the DHEA-s/cortisol ratio in subgroups 1.1 (0.86) and 1.2 (0.95), which indicates the effectiveness of dapagliflozin therapy. Conclusions. The results obtained confirm the feasibility of using SGLT2i therapy and its effectiveness in optimizing morpho-metabolic characteristics in type 2 diabetes patients with different phenotypes, especially in those with a non-obese phenotype.