OBJECTIVE: To compare the effectiveness of antihyperglycemic therapies in type 2 diabetic patients with poor glycemic control (baseline glycosylated hemoglobin [HbA1C] > 8%). STUDY DESIGN: Longitudinal (cohort) study. METHODS: Study patients were 4775 type 2 diabetic patients who initiated new antihyperglycemic therapies and maintained them for up to 1 year. The study setting was Kaiser Permanente Northern California Medical Group, an integrated, prepaid, healthcare delivery organization. Treatment regimens were 1 or more of the following: insulin, thiazolidinediones, sulfonylureas, biguanides (metformin), or other less frequently used options (including meglitinides or alpha-glucosidase inhibitors). RESULTS: In this cohort, the mean HbA1C was 9.9% when therapy was initiated. Within 1 year, there was a drop of 1.3 percentage points in the mean HbA1C (to 8.6%), and 18% of new initiators achieved HbA1C values of < or = 7%. After adjusting for baseline clinical differences, the proportion of patients treated to goal was greatest among those receiving thiazolidinediones in combination (24.6%-25.7%) or a regimen of metformin and insulin (24.9%), while the least success was experienced by those receiving sulfonylureas alone (12.5%) or insulin-sulfonylureas regimens (10.9%). The probability of achieving the target goal was most strongly predicted by the level of glycemic control before initiation, but patient behaviors (eg, frequent self-monitoring, lower rates of missed appointments) also were strongly associated with greater levels of control. CONCLUSION: Overall, therapy initiation resulted in an impressive population-level benefit. However, since most new initiators still had not achieved good control within 12 months, careful monitoring and prompt therapy intensification remain important.