OBJECTIVES: Patients’ preferences and evaluation of treatment benefits/risks from patient’s perspective are increasingly being considered in decision-making regarding treatment option. The goal of this prospective, open, observational study was to evaluate QoL and hypoglycemia burden in T2DM patients treated with vildagliptin and metformin as compared to those treated with sulphonylureas (SU) and metformin. METHODS: A total of 194 T2DM patients previously on oral monotherapy were enrolled in the study. 111 patients were selected by their treating physician to receive vildagliptin and metformin (cohort 1 – mean age 58 yrs; male/female 43/68) and 83 patients – SU and metformin (cohort 2– mean age 58.6 yrs; male/female 27/56). Patient-reported outcomes were assessed at base-line and after approximately 3 mo using the SF-36 and the Hypoglycemia Perspectives Questionnaire (HPQ). For comparisons adjustment for age, sex, disease duration, complications and comorbidities was made. RESULTS: QoL parameters for all SF-36 scales were significantly higher in cohort 1 as compared to cohort 2 after 3 mo of therapy (р<0.01). Switch to vildagliptin plus metformin therapy was accompanied with remarkable increase of Integral QoL Index (р<0.0001) whereas no changes of Integral QoL Index were observed after switch to SU plus metformin. After 3 mo of combination therapy the number of self-reported symptomatic hypoglycemic events was 16% in cohort 1 versus 70% in cohort 2; 12% of pts had severe hypoglycemic events in cohort 2. SU plus metformin therapy was accompanied with significant hypoglycemia burden – after switching worries, awareness and symptom concern increased (р<0.001). No changes were observed in cohort 1. The changes in glycemic control were the same in both cohorts: DHbA1c=0.8%. CONCLUSIONS: Benefits of vildagliptin plus metformin combination therapy in terms of improved QoL and reduced hypoglycemia burden in T2DM patients were shown. This therapy is an effective and preferable treatment in daily medical practice from patient's perspective.