Clinical Impact of ITCA 650, a Novel Drug-Device GLP-1 Receptor Agonist, in Uncontrolled Type 2 Diabetes and Very High Baseline HbA1c: The FREEDOM-1 HBL (High Baseline) Study

OBJECTIVE ITCA 650 is a subdermal osmotic mini-pump that continuously delivers exenatide subcutaneously for 3-6 months. The efficacy, safety, and tolerability of ITCA 650 added to diet and exercise alone or combined with metformin, sulfonylurea, or thiazolidinedione monotherapy or a combination of these drugs was evaluated in poorly controlled patients with type 2 diabetes (T2D) who were ineligible for participation in a placebo-controlled study (FREEDOM-1) because of severe hyperglycemia (HbA(1c) > 10% [86 mmol/mol]). RESEARCH DESIGN AND METHODS This 39-week, open-label, phase 3 trial enrolled patients aged 18-80 years with HbA(1c) > 10% to <= 12% (86-108 mmol/mol) and BMI 25-45 kg/m(2). Patients received ITCA 650 20 mu g/day for 13 weeks, then 60 mu g/day for 26 weeks. The primary end point was change in HbA(1c) at week 39. RESULTS Sixty patients were enrolled. At baseline, mean HbA(1c) was 10.8% (94.7 mmol/mol) and mean (+/- SD) duration of diabetes was 8.6 (+/- 5.3) years. At week 39, there was a mean reduction in HbA(1c) of -2.8% (-30.3 mmol/mol; P < 0.001 vs. baseline) and in body weight of -1.2 kg (P = 0.105), and 25% of patients achieved HbA(1c) < 7% (53 mmol/mol). A reduction in HbA(1c) of >= 1% (>= 10.9 mmol/mol) occurred in 90% of patients. The most common adverse events were nausea, vomiting, diarrhea, and headache. Gastrointestinal adverse events were generally transient and subsided over time; only 4 patients (6.7%) discontinued for gastrointestinal events. CONCLUSIONS Treatment with ITCA 650, the first injection-free glucagon-like peptide 1 receptor agonist, resulted in significant improvements in glycemic control in poorly controlled long-standing T2D patients with a high baseline HbA(1c) > 10%.