To examine trends in the prescribing patterns and the costs of pharmacologic treatment of type 2 diabetes mellitus (T2DM) across different therapeutic classes. A large national claims database was employed to identify patients with T2DM using antidiabetic agents between January 2007 and December 2014. We assessed trends in medication use and expenses in six different monotherapies (metformin, sulfonylurea, meglitinide, thiazolidinedione, Glucagon-like peptide-1 receptor agonists (GLP1 RAs), and dipeptidyl peptidase-4 (DPP4) inhibitors) as well as combination therapies of these medications with metformin. Throughout the study period, metformin and sulfonylurea were the most commonly used monotherapies, representing 71% to 77% of total use. Thiazolidinedione use as monotherapy decreased from 19% in 2007 to 4% in 2014. Meglitinide use also decreased from 2% in 2007 to 1% in 2014. However, GLP1 RAs and DPP4 inhibitor use increased from 4% to 6% and 4% to 13%, respectively during this time period. Among combination therapies, DPP4 inhibitor/metformin substantially increased from 7% in 2007 to 67% in 2014 while sulfonylurea/metformin and thiazolidinedione/metformin combination decreased from 63% to 26% and 31% to 7%, respectively. Accordingly, spending on thiazolidinedione considerably decreased during the study period whereas spending on GLP1 RA and DPP4 inhibitor increased. Increases in the use of DPP4 inhibitor/metformin accounted for increases in spending on this combination therapy. Spending on sulfonylurea/metformin and thiazolidinedione/metformin decreased during the period. Overall, spending on antidiabetic medications from public sector (e.g., Medicare and Medicaid) increased from 25% in 2007 to 35% in 2014. Prescribing patterns and spending on different drug classes to treat T2DM have changed substantially over the past years. Pharmacologic treatments with thiazolidinedione and meglitinide have decreased while treatments with GLP1 RA and DPP4 inhibitor have increased. Future research is needed to assess whether these pharmacological treatment changes have resulted in changes in various outcomes among patients with T2DM.