OBJECTIVES: Prevalence of diabetes mellitus is increasing globally in most developed and developing countries and Dipeptidyl peptidase-4 inhibitors (Gliptins) are recently introduced class of drugs for type 2 diabetes mellitus which shows good glycemic control. It is a prospective interventional pilot study aimed to determine the efficacy of add-on vildagliptin therapy to metformin in type 2 diabetes mellitus patients for a period of 6 months in south Indian resource limited settings METHODS: A total of 185 patients were enrolled into the study. The study subjects were assigned into three groups based on their existing treatment (initiated within one month) i.e., group I (vildagliptin and metformin), group II (vildagliptin alone) and group III (metformin alone). They were also assessed for baseline demographic characteristics. Medication adherence was measured to ensure that patients are complies with the treatment. The clinical endpoint was estimated by using various variables like quality of life and other clinical endpoints such as RBS, PPBS after three months of specific treatment through direct interview and by referring the medical case records. RESULTS: The results show that there is no significant difference in individual groups in terms of demographic characteristics             (P >0.01). And all the present study subjects are found to have more than 90 % of medication adherence.  We observed high level of significant improvement in group I (93.18±3.76) subjects whereas low level of improvement in group III subjects (90.4±4.13) after the relevant treatment (P = 0.003). Group I subjects are also found to have good glycaemic control (RBS, FBS and PPBS) than any other treatment groups P<0.01). CONCLUSIONS: Add on vildagliptin therapy to metformin might improve the quality of life of type 2 diabetes mellitus patients and might be useful to bring the glycemic levels under control in type 2 diabetic patients in  South Indian resource limited settings.