Randomized Trial of Continuous Subcutaneous Delivery of Exenatide by ITCA 650 Versus Twice-Daily Exenatide Injections in Metformin-Treated Type 2 Diabetes

OBJECTIVE: To evaluate ITCA 650, a continuous subcutaneous miniature osmotic pump delivery system of exenatide versus twice-daily exenatide injections (Ex-BID) in subjects with type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted a randomized, two-stage, 24-week, open-label, phase 2 study in type 2 diabetes inadequately controlled with metformin. Stage I: 155 subjects were randomized to 20 or 40 μg/day of ITCA 650 or Ex-BID 5→10 μg. Stage II: 131 subjects were rerandomized to 20, 40, 60, or 80 μg/day of ITCA 650. Change from baseline for HbA(1c), weight, and fasting plasma glucose were evaluated at weeks 12 and 24. RESULTS: HbA(1c) was significantly lower in all groups after 12 and 24 weeks. Stage I: mean change in HbA(1c) from a mean baseline of 7.9–8.0% was −0.98, −0.95, and −0.72% for the 20 and 40 μg/day ITCA 650 and Ex-BID groups, respectively, with 63, 65, and 50% of subjects achieving HbA(1c) levels ≤7% (P < 0.05). Stage II: significant (P < 0.05) reductions in HbA(1c) (∼1.4% from baseline) were achieved with 60 and 80 μg/day ITCA 650, and 86 and 78% of subjects achieved HbA(1c) ≤7% at 24 weeks; respectively. Weight was reduced by 2.8–3.7 kg (P < 0.05) at 24 weeks in all except the 20→20 μg/day group. ITCA 650 was well tolerated; nausea was lower and transient with 20 μg/day relative to Ex-BID; and 60 μg/day had the best profile of tolerability and HbA(1c) lowering. CONCLUSIONS: ITCA 650 significantly reduced HbA(1c) and weight and was well tolerated. The 20→60 μg/day regimen was considered the best dose for further examination in phase 3.