Aims Evaluate the efficacy and tolerability of ITCA 650 in subjects with type 2 diabetes treated for up to 48 weeks. Methods This was a 24-week extension to a randomized, 24-week, open-label, phase 2 study in subjects with type 2 diabetes inadequately controlled with metformin. Subjects received ITCA 650mg (20, 40, 60 or 80μg/day). Mean changes for HbA1c, weight, and fasting plasma glucose (FPG) were evaluated. Results Mean changes in HbA1c from baseline to week 48 ranged from −0.85% to −1.51%. At week 48, ≥64% of subjects with an HbA1c ≤7% at week 24 maintained an HbA1c ≤7%. The incidence of adverse events (AEs) was dose-related and ranged from 13.3% with 20μg/day to 37.5% with 80μg/day. Most AEs were mild and transient; the incidence of nausea declined from 12.9% to 9.5% over the 24-week extension. One subject on ITCA 650 80μg/day experienced mild intermittent vomiting. Three (3.5%) subjects experienced severe AEs, but none were considered related to study drug. Conclusion Significant changes in HbA1c, body weight, and FPG attained with ITCA 650 were maintained to 48 weeks. The incidence of AEs was lower in the 24-week extension than in the initial 24-week treatment phase.