OBJECTIVES: Patient-reported outcomes is an effective way to evaluate risks/benefits of antidiabetic treatment in patients with T2DM and has been increasingly considered in treatment decision-making. The goal of this multicenter observational study was to evaluate quality of life (QoL) and hypoglycemia burden in T2DM patients receiving oral combination therapy in a real-world setting. METHODS: A total of 160 T2DM patients receiving vildagliptin plus metformin (mean age 59.6 yrs; male/female 25/57) or sulphonylureas (SU) plus metformin (mean age 65.1 yrs; male/female 23/55) for at least 6 months (mean 6.5 yrs, 0.6–17 yrs) were enrolled in the study. All the patients completed the QoL questionnaire SF-36 and the Hypoglycemia Perspectives Questionnaire. Integral QoL Index (IQoLI) was calculated on the basis of SF-36. Group comparisons were made using χtest and analysis of covariance (ANCOVA) with adjustment for age, sex, disease duration, HbA1c level, complications, comorbidities. RESULTS: Patients receiving SU plus metformin had worse role physical and role emotional functioning, vitality, social functioning and pain (p<0.01) than those receiving vildagliptin plus metformin; their IQoLI was significantly lower than in the latter group (p<0.05). They exhibited more pronounced QoL impairment as compared to those receiving vildagliptin plus metformin (p=0.002). 50% patients on SU plus metformin vs 27% patients on vildagliptin plus metformin experienced hypoglycemia during the last 6 months (p<0.003). In the group on SU plus metformin 9.6% patients had severe hypoglycemia and 4.1% – nocturnal hypoglycemia; patients on vildagliptin plus metformin – only non-severe hypoglycemia and no nocturnal hypoglycemia episodes. SU plus metformin therapy was accompanied with pronounced hypoglycemia burden as compared to vildagliptin plus metformin therapy. CONCLUSIONS: Results of this real-world study demonstrate benefits of vildagliptin plus metformin combination therapy in T2DM patients as compared to SU plus metformin therapy in terms of better QoL and lower risks of treatment in terms of less hypoglycemia burden.