Evaluating the effectiveness of early dipeptidylpeptidase-4 inhibitors combined therapy for type 2 diabetes mellitus
Keywords:type 2 diabetes mellitus, combined therapy, DPP4 inhibitors, hypoglycemia
Introduction: type 2 diabetes is a chronic degenerative disease with inevitable progression. Its treatment is performed as an intensification of the therapy in response to the deterioration of β-cell function. Careful selection of the therapy from an early stage of the disease is used in order to reduce the risk of developing long-term complications of diabetes.
Objective: evaluate the efficacy and safety of fixed lowdose combinations of dipeptidylpeptidase-4 (DPP-4) inhibitors with metformin in patients suffering from type 2 diabetes with inadequate glycemic control.
Materials and Methods: 56 patients participated in the study (42 women and 14 men, with the average age being 57,8 ± 2,17 years) suffering from type 2 diabetes with inadequate glycemic control (mean HbA1c 8,89 ± 0,31%) treated previously with oral hypoglycemic agents + basal insulin. An average duration of type 2 diabetes was 3,5 ± 1,13 years. Safety of the therapy was assessed by the number of hypoglycemic reactions (clinically confirmed with glycemia <3,3 mmol/L or those with symptomatic blood glucose <4,0 mmol/L). The first group of patients (29 subjects) received combined therapy consisting of vildagliptin with metformin + basal insulin, second group of patients (27 subjects) – received combined therapy consisting of glibenclamide with metformin + basal insulin. Follow-up period lasted for 24 weeks, during which 2 visits were made: initial visit and final visit.
Results: by the end of 24 weeks of follow-up significant positive changes in glycated hemoglobin, fasting plasma glucose (FPG), postprandial blood glucose (PBG) (p<0,01) were noticed in patients of both groups. HbA1c levels decreased by an average of 1,81 % in the vildagliptin group and by 1,65 % in the glibenclamide group. Levels of FPG and PBG in vildagliptin group declined by an average of 3,05 and 5,34 mmol/L, respectively. The levels of FPG and PBG in glibenclamide group declined by an average of 3,67 and 4,76 mmol/L, respectively. Thus it was shown a comparable efficacy of combination drug treatment consisting of vildagliptin and glibenclamide.
However, significant differences in the incidence of side effects were found between treatments schemes despite the equal effectiveness of treatment in improving control of diabetes. Episodes of mild hypoglycemia were reported only in 7 subjects on combinative treatment consisting of vildagliptin with metformin, which represents less than 25% of the entire population of patients. No events of moderate and severe hypoglycemia were reported. For comparison, in glibenclamide group 8 patients reported episodes of mild hypoglycemia and 5 subjects noted moderate hypoglycemia, which amounted to more than 48 % of the entire population of patients.
Conclusion: DPP-4 inhibitors in combination with metformin provide effective glycemic control without risk of hypoglycemia. One of the most effective treatments is the use of fixed low-dose combination of vildagliptin and metformin. Adding of DPP-4 inhibitors to insulin reduces the incidence and severity of hypoglycemia.