OBJECTIVES: We previously identified a correlation between weight loss and glycemic control in patients with type 2 diabetes (T2DM) newly treated with oral or GLP-1 inhibitor therapy in the real-world setting. This study expands on those findings by including previously treated patients and patients initiating insulin.  METHODS: This cohort study included T2DM patients age ≥18 years in an electronic medical record database from 2008-2011 prescribed a class of anti-diabetic not previously used (index date), and with a baseline HbA1c ≥7.0%. Weight and HbA1c changes from baseline were assessed at 6-months. Patients who lost ≥3% of body weight and attained HbA1c goal (<7.0%) were identified. Logistic regression was used to describe the association between weight loss and glycemic control controlling for confounding factors, including initiation of insulin vs. other therapies.  RESULTS: The study included 861 patients. Mean (SD) age was 58.7 (12.3) years; 54.8% were male. Most patients (85.9%) were prescribed a non-insulin agent. Baseline HbA1c was 8.7% (1.6); weight was 103.6 kg (23.6). At 6 months, mean weight change was -1.6 (5.3) kg (p=0.13) and 31.8% lost weight. Mean change in HbA1c was -1.2% (1.8) (p<0.001). Overall, 42.9% attained HbA1c goal while 64.2% of patients who lost weight and 32.9% of those who did not lose weight (p<0.001) attained goal. The OR for attaining HbA1c goal with weight loss ≥3% vs. no weight loss was 3.60 (95% CI 2.66, 4.87) and was not significantly affected by insulin use.  CONCLUSIONS: Patients with uncontrolled T2DM prescribed a new class of anti-diabetic and who lost weight were more likely to attain HbA1c goal at 6-months than those who did not lose weight. These data are consistent with T2DM treatment guidelines that emphasize the importance of weight loss and prioritization of anti-diabetes agents that are not associated with weight gain.