Objective: Changes in drug treatment of diabetes in the United States were studied using data from the National Health and Nutrition Examination Survey 1999~2010. Methods: Data on 3094 participants aged ≥ 20 with diagnosed type 2 diabetes were analyzed. The use of medications for lowering blood glucose, blood pressure (BP), and lipids in the past month was assessed by questionnaire. Data from two survey cycles were combined together to produce estimates for each 4-year period. Results: Utilization of all 3 types of medications increased significantly from 1999~2002 to 2007~2010 (P < 0.01). Usage of metformin increased from 34.8% to 53.8% during this period (P < 0.001), which was the most common medication for diabetes in 2003~2010, and half of subjects taking metformin could achieve glycated hemoglobin less than 7.0% in 2007~2010. Dipeptidyl peptidase-4 (DPP-4) inhibitors, approved in 2007, were used by 7.4% of the participants in 2007-2010. Usage of angiotensin receptor blockers (ARB) and beta-blockers increased from 7.4% to 21.4%, and from 15.3% to 31.8%, respectively, across the 12-year period (both P < 0.001). Usage of statins doubled in 1999-2010 and 52.2% of subjects took statins by 2007~2010 (P < .001). Conclusion: There were significant increases in the use of glucose, BP and lipid lowering medications during 1999-2010, especially in the use of metformin, ARB and beta-blockers. The increased BP drug prescription could lead to improved BP control. Metformin is the recommended first line drug for diabetes, while DPP-4 inhibitors began to be used after their introduction. Although statins were widely used about half of the participants did not take them.