Objective: This study evaluated real world outcomes of A1C and weight in patients with type-2 diabetes (T2DM) initiating exenatide therapy. Methods: Patient data were extracted from the General Electric (GE) electronic medical record (EMR) research database from January 1, 2000 through September 30, 2007. Patients were =18 years old with T2DM defined by ICD-9 codes, =2 fasting blood glucose levels =126mg/dL, or glycosylated hemoglobin (A1C) over 7.0%. Patients had prescription orders in the previous 395d for metformin (MET), a sulfonylurea (SU) or a thiazolidinedione (TZD) as monotherapy or in combination. Baseline A1C, weight and BMI were documented 45d prior to 15d post-exenatide initiation and ±45d at 6mo post-exenatide initiation. Results: For the 2086 patients with 6mo of follow-up data, baseline mean (±SD) A1C was 8.4±1.2%, weight was 243.4±54.8lbs and BMI was 38.5±7.9kg/m2. Upon initiation of exenatide, 363 (17.4%), 147 (7.1%) and 84 (4.0%) were on MET, SU or TZD monotherapy respectively, 524 (25.1%) and 257 (12.3%) were on MET with TZD or SU, and 711 (34.1%) were on all three. Overall A1C change at 6mo (n=878) was -0.7%. When exenatide was added to MET, SU or TZD monotherapy, changes were -0.9% (p<0.0001), -1.0% (p<0.0001) and -0.8% (p<0.0032) respectively. A1C lowering ranged from -0.5% to -0.8% with multiple oral antidiabetic drugs (OADs) (p<0.0001). Overall weight loss (n=1784) was -6.1 lbs (p<0.0001). In the 6mo following addition of exenatide to prior monotherapy, 14%, 23% and 45% of patients discontinued MET, SU and TZD respectively. Similar discontinuations were seen in the multiple OAD groups. Conclusion: The average baseline A1C (8.4%) and BMI (38.5kg/m2) is high in this primary care T2DM population, suggesting difficulty in the real world to achieve A1C and body weight goals. Exenatide therapy demonstrated significant reductions in A1C and weight over 6mo with decreases in concomitant medications.