Clinical Impact of ITCA 650, a Novel Drug-Device GLP-1 Receptor Agonist, in Uncontrolled Type 2 Diabetes and Very High Baseline HbA_1c: 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 >10% [86 mmol/mol]). RESEARCH DESIGN AND METHODS: This 39-week, open-label, phase 3 trial enrolled patients aged 18-80 years with HbA >10% to ≤12% (86-108 mmol/mol) and BMI 25-45 kg/m. Patients received ITCA 650 20 μg/day for 13 weeks, then 60 μg/day for 26 weeks. The primary end point was change in HbA at week 39. RESULTS: Sixty patients were enrolled. At baseline, mean HbA 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 of -2.8% (-30.3 mmol/mol; < 0.001 vs. baseline) and in body weight of -1.2 kg ( = 0.105), and 25% of patients achieved HbA <7% (53 mmol/mol). A reduction in HbA 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 >10%.