OBJECTIVES Clinical trials have reported A1C reductions of 0.7% over 24 weeks for sitagliptin monotherapy and when added to metformin (baseline A1C = 8.0% for both). When added to pioglitazone the mean A1C reduction was 0.9% (baseline A1C = 8.1%). With monotherapy 45% of patients achieved A1C <7.0%. METHODS Patient characteristics and real-world effectiveness of sitagliptin were investigated using a large US claims database. Patients with new prescription claims for sitagliptin between 10/1/06 and 3/31/07 and ≥12 months pre- and post-index eligibility were included (n = 3719). Mean (SD) age was 56.0 (±10.0) and 39% were female. Co-morbidities included: hypertension (84%), dyslipidemia (83%), and other cardiovascular disease (25%). The starting dose was 100 mg for 93% of patients. Concomitant antihyperglycemic medications at index (-100 to +15 days post index) included metformin (58%), thiazolidinediones (41%), sulfonylureas (37%) and insulin (16%). Seven percent had no concomitant antihyperglycemic medications. RESULTS The mean (SD) number of concomitant medications was 1.9 (±1.0). Insulin use increased from 16% to 25% (p<.0001), in the 12 month post-index period. Other concomitant medications showed little change. The medication possession ratio (days supply/365 days) in patients with >1 prescription claim was 74±29%. Clinical effectiveness was measured in patients with baseline (6 months pre-index - 1 month post index) and post-index (60-365 days) A1C data (n = 102). Mean (SD) baseline A1C was 7.6% (±1.0) with an absolute reduction of 0.2% (±1.1) [mean duration of follow-up = 246.0 (±81.6) days]. Of 72 patients with a baseline A1C ≥7.0%, 21 (29%) achieved an A1C goal of <7.0%. CONCLUSIONS This study reports real-world analyses of sitagliptin patient characteristics and effectiveness. Adherence to therapy was similar to that for other oral antihyperglycemic drugs, but mean reduction in A1C and percent to goal were less than in clinical trials, despite an increase in the percent of patients using insulin.