Efficacy and Safety of ITCA 650, a Novel Drug-Device GLP-1 Receptor Agonist, in Type 2 Diabetes Uncontrolled With Oral Antidiabetes Drugs: The FREEDOM-1 Trial

OBJECTIVE ITCA 650 (exenatide in osmotic mini-pump) continuously delivers exenatide subcutaneously for 3-6 months. Two doses of ITCA 650 were compared with placebo in patients with uncontrolled type 2 diabetes. RESEARCH DESIGN AND METHODS This 39-week, phase 3, double-blind, placebo-controlled trial randomized 460 patients aged 18-80 years with glycated hemoglobin (HbA(1c)) 7.5-10% [58-86 mmol/mol] 1: 1: 1 to placebo, ITCA 650 40 mg/day, or ITCA 650 60 mg/day. Primary end point was change in HbA(1c) at 39 weeks. RESULTS Least squares (LS) mean change from baseline HbA(1c) was 21.1% [212.2 mmol/mol] and 21.2% [213.2 mmol/mol] for ITCA 650 40 and 60 mg/day, respectively (P < 0.001 vs. placebo20.1% [21.3mmol/mol]). In a prespecified analysis, greater HbA(1c) reductions occurred in patients not receiving sulfonylureas (SUs) versus those receiving SUs (21.7% vs. 21.2% [218.6 and 213.1 mmol/mol]). At week 39, HbA1c < 7% [53 mmol/mol] was attained in 37%, 44%, and 9% of ITCA 650 40 mg/day, ITCA 650 60 mg/day, and placebo groups, respectively (P < 0.001 each dose vs. placebo). LS mean change from baseline body weight was 22.3 kg and 23.0 kg for ITCA 650 40 and 60 mg/day, respectively (P <= 0.015 vs. placebo-1.0 kg). Nausea was the most common adverse event (AE) and subsided over time. Discontinuation for gastrointestinal AEs occurred in 7.2% with ITCA and 1.3% with placebo. Most AEs associated with procedures to place and remove ITCA 650 were mild and transient. CONCLUSIONS ITCA 650 significantly reduced HbA(1c) and weight compared with placebo and was well tolerated in patients with uncontrolled type 2 diabetes on oral antidiabetes medications.