The Clinical use of glimepiride in patients with type 2 diabetes mellitus, uncontrolled on combination of DPP4-inhibitors and metformin: results of ESCALATION observational study

Background. Russian guidelines for T2DM management 2015 recommend intensification to triple combination therapy in patients not reaching glycaemia treatment targets on dual oral antidiabetic therapy for 6 months. Despite this, clinical experience shows that physicians may also switch one component of the dual therapy, or add the third component of the therapy. This study sought to assess the effect of physician-led prescription of glimepiride (GLIM) to individuals with T2DM uncontrolled by metformin (MET) and DPP-inhibitor. Material and methods. This observational study was carried out in real clinical practice in 142 Russian clinical centers, among 1447 T2DM patients, which consume glimepiride according to medical disposal. Entry criteria included 18—80 years male and female with HbA1c≥ 7,6% и ≤10 (during 2 month) and uncontrolled carbohydrate metabolism by individualized HbA1c target level by MET(in a dose ≥1500 mg/per day) and DPP-4i for ≥3 months, which doctor prescribed glimepiride in mono- or combination therapy. Duration of observation after inclusion into research was 24 weeks. Results. Patients were prescribed glimepiride as part of three-component therapy — GLIM+MET+DPP-4i (54.5%), two-component — GLIM+MET (34.4%), in other combinations — GLIM+other (11.1%). Mean HbA1c reduction at 24 weeks was 1.49±0.71%, and fasting blood glucose (FBG) reduction — 2.18±1.38 mmol/l. Significant changes in glycemic control in different groups of patients were not committed. Postprandial blood glucose (PPG, mmol/l) on an average decreased — 3.00±1.71, in groups GLIM+MET+DPP-4i, GLIM+MET and GLIM+other 2.98±1.63; 3.07±1.81 и 2.95±1.84. At week 24, body mass index (BMI, kg/m2 )was overall decrease by 0.36±1.99 and not significantly reduced in the GLIM+MET+DPP-4i, GLIM+MET and GLIM+other groups. Adverse events (AEs), inclusive of symptomatic hypoglycaemia, were reported in 370 patients (25.8% of all participants). In GLIM+MET+DPP-4i, GLIM+MET and GLIM+other groups frequency of symptomatic hypoglycaemia composed 13.2, 8.5 и 14.5%. Incidence of asymptomatic hypoglycaemia was reported at 8.4% of patient. In GLIM+MET+DPP-4i, GLIM+MET and GLIM+other groups it were 8.4, 7.3 и 11.9% , with maximum in GLIM+other group. There were no significant differences in the proportions of patients with hypoglycaemic episodes between other study groups. No episodes of severe hypoglycaemia or serious AEs were reported. Conclusion. More than a half of incidences of uncontrolled T2DM by metformin and DPP-4 inhibitor combination treatment in real-life clinical practice is intensify by prescribing three-component treatment setting. Approximately, in third cases the choice of the therapeutic approach depend on switch of iDPP-IV for the GLIM. Further 11.1% composed combinations glimepiride+ iDPP-IV (DRC). Various combinations of GLI with MET and/or iDPP4 provided improvement of glycemic control, affecting of HbA1c, FPG and PPG. During the study, there was no significant difference in glycemic control between different types of the therapy. Episodes of symptomatic hypoglycemia were more frequent in the DRC group compared with the group GLY+MET. No severe hypoglycemic events and no influence for body weight were reported in research indicating the safety of GLIM at T2DM patients uncontrolled by metformin and DPP-4 inhibitor combination therapy.