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 g/day of ITCA 650 or Ex-BID 510 g. Stage II: 131 subjects were rerandomized to 20, 40, 60, or 80 g/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 g/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) (approximate to 1.4% from baseline) were achieved with 60 and 80 g/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 2020 g/day group. ITCA 650 was well tolerated; nausea was lower and transient with 20 g/day relative to Ex-BID; and 60 g/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 2060 g/day regimen was considered the best dose for further examination in phase 3.