Glucocentric and cardiocentric approaches to achieving type 2 diabetes compensation

Abstract

Background. Monotherapy for type 2 diabetes (T2DM) has been found to be effective only for a limited time. At the same time, the rationality of drug combinations remains an important component of successful management of T2DM. In this context, given the complex multifactorial pathogenesis of T2DM, it is optimal to influence various mechanisms of hyperglycemia. The purpose of the study is to determine the effectiveness and safety of additional administration of a combination of metformin and glimepiride in patients with type 2 diabetes with a glycated hemoglobin (HbA1c) level of 8.5–9.5 % who took dapagliflozin alone for at least three months. Materials and methods. Fourteen men (mean age 57.9 ± 8.4 years) and 18 women (mean age 58.2 ± 9.3 years) with T2DM were included in the study. The average duration of T2DM was 9.7 ± 4.2 years. The patients were in a state of decompensation of T2DM (HbA1c over 8.5 %) against the background of dapagliflozin monotherapy in the maximum dose for at least three previous months. In addition to dapagliflozin (10 mg/day), patients were prescribed a combination of metformin and glimepi­ride (Duglimax tablets, 500 mg/2 mg once a day) for three months. Results. The average level of HbA1c in 32 patients with T2DM was 9.72 ± 0.81 %, fasting plasma glucose was 10.71 ± 1.42 mmol/l. Three months after the start of a combined treatment, the HbA1c level decreased significantly to 7.54 ± 0.46 % (p < 0.05). The average reduction in HbA1c after switching to additional metformin therapy with glimepiride was 1.48 ± 0.38 %. The proportion of patients who achieved HbA1c < 7.5 % was 34.5 % after 3 months (p < 0.05). The effectiveness of the additional administration of metformin and glimepiride is also confirmed by the high percentage of patients (12.5 %) who achieved HbA1c < 7.0 % (p < 0.05). The level of fas­ting plasma glucose decreased to an average of 7.19 ± 1.06 mmol/l after 3 months. The average decrease reached 3.06 ± 1.08 mmol/l, which in relative terms was 31.4 ± 8.7 % of baseline. No cases of hypoglycemia or other adverse events were registered during the entire study period. Conclusion. The analysis of indicators in 32 patients with type 2 diabetes who had a high level of HbA1c (over 9 %) against the background of dapagliflozin monotherapy allowed us to conclude that it is necessary to intensify the therapy by additionally prescribing a combination of metformin and glimepiride for achieving the target levels of HbA1c. Glucocentric and cardiocentric views on T2DM can be reconciled and integrated by using a combination therapy to address the different etiopathological features of the disease from the very beginning of treatment.