OBJECTIVES: The expenditures for oral anti-diabetic medications have grown markedly over the last decade. This study examined the patterns of use and expenditures of individual anti-diabetic drug classes between 1999 and 2009. METHODS: We obtained a 0.2% sample of monthly ambulatory claims from Taiwan National Health Insurance. We assessed volume (DDD/patient/quarter) and government reimbursed costs (costs/patient/quarter) for each antidiabetic drug group over 11 years. RESULTS: Between 1999 and 2009, the number of diabetic prescription (patient) increased steadily at an average rate of 12.2% per year. Utilization of oral anti-diabetic drugs increased from 246.05 ddd/patient in 1999_Q1 to 334.28 ddd/patient in 2003_Q2, then began to decrease; this change was due to a marked reduction of sulfonylureas (from 235.88 ddd/patient [79.16% of total DDDs] in 2003_Q2 to 140.37 ddd/patient [58.15% of total DDDs] in 2009_Q4). Use of biguanides was relatively stable over the study period (average rate 61.56 ddd/patient; 23% of the market; 646.53 NT$/patient). In 2004_Q2, there was clear shift in use from an older gliclazide (account for 48.40% of sulfonylureas in 2004_Q2) to a newer agent, glimepiride (24.12%). Rosiglitazone’s use (70.37% of thiazolidinediones) dropped rapidly from 2004_Q2 due to the safety concern of cardiovascular risk. The total costs of anti-diabetic medications increased from NT$1931.91/patient in 1999_Q1 to NT$3446.95/patient in 2004_Q2, then began to subsequently a downward trend (NT$2380.50/patient in 2009_Q4), primarily due to a substantial reduction in thiazolidinediones (1,100.57 NT$/patient [29.92% of total costs] and 2004_Q2 to 569.63 NT$/patient [23.92% of total costs] in 2009_Q4). CONCLUSIONS: Sulfonylureas and biguanides, generally recommended as first-line therapies, dominated the Taiwan market for diabetic management (86%~100% of total DDDs) over the last decade. Uptake of newer, more expensive agents, namely thiazolidinediones and alpha-glucosidase inhibitors, was small. Our results suggest the utilization pattern of oral anti-diabetic medications in Taiwan is overall consistent with clinical guidelines.