OBJECTIVES: To conduct pharmacoepidemiological research and cost-minimization analysis of oral antidiabetic medications and insulins in Lithuania. METHODS: Medications were grouped according to the ATC classification system. Our research results were reported in DDDs per 1000 inhabitants per day (DDD/TID). Calculations of drug prices and total expenditures on antidiabetic medications were made by using data from National Patient Funds Price List in 2006 - 2009 years. Reference pricing methodology was used to accomplish our cost-minimization analysis. RESULTS: Total consumption of hypoglycaemic agents increased by 33% from 21.54 DDD/TID in 2006 to 28.72 DDD/TID in 2009. Utilization of insulin increased by 30% reaching the value 9.43 DDD/TID in 2009 and oral antidiabetic medications increased by 35% - 19.29 DDD/TID in 2009. Total expenditures on hypoglycaemic agents increased by 23% from LTL 57.138 mlln in 2006 to LTL 70.531 mlln in 2009 (1EUR=3.4528LTL). Single DDD prices ranged from 0.70 LTL/DDD to 5.01 LTL/DDD of oral antidiabetics, and from  5.67 LTL/DDD to 2.97 LTL/DDD for insulins. With reference to meta-analysis and NICE recommendations, considering the similar efficacy and safety within drug classes, cost-minimization analysis using the reference-based pricing could be implemented and total expenditures could be decreased by 27% (saving LTL 19 mlln. yearly). CONCLUSIONS: Our findings suggest that implementation of reference-based pricing could be a strong fiscal measure helping to rationalize increasing direct health-care expenditures by 27%.