Continuous SQ exenatide lowers HbA1c, weight with better tolerability

June 29, 2011

Continuous subcutaneous delivery of exenatide using an investigational infusion device resulted in substantial decreases in glycosylated hemoglobin (HbA1c) in patients with type 2 diabetes without the nausea associated with twice-daily exenatide injections, reported investigators in an extension of a phase II study.

Continuous subcutaneous delivery of exenatide using an investigational infusion device resulted in substantial decreases in glycosylated hemoglobin (HbA1c) in patients with type 2 diabetes without the nausea associated with twice-daily exenatide injections, reported investigators in an extension of a phase II study.
     Patients in the study also lost between 2.7 and 4.9 kg of baseline body weight, reported Julio Rosenstock, MD, Clinical Professor of Medicine at the University of Texas Southwestern Medical School in Dallas.
     The study evaluated continuous subcutaneous delivery of exenatide with an implantable osmotic delivery system that delivers the glucagon-like peptide-1 (GLP-1) receptor agonist constantly at specified doses (ITCA 650). The device is replaced every 3 months in a 10- to 15-minute office procedure under local anesthesia.
     The investigators enrolled 155 patients treated with metformin who had HbA1c levels of 7% to 10% in a 24-week study. The patients were randomly assigned to treatment with exenatide in doses of 20, 40, 60, or 80 mcg/day, following 12 weeks of either continuous delivery of 20- to 40-mcg/day doses or twice daily 10-mcg injections (20 mcg/day total dose).
     At week 24, the participants were offered the option of continuing on a 24-week extension study at their current dose.
     HbA1c changes from baseline at week 48 were -1.0% on the 20-mcg dose; -1.1% on the 40-mcg dose; -1.5% on the 60-mcg dose; and -1.4% on the 80-mg dose (P<.0005 for all doses).
     Weight changes from baseline to week 48 were 2.7 kg in the 20-mcg dose (not significant); -4.9 kg in the 40-mcg group (P<.0005); -3.5 kg in the 60-mcg group (P<.05); and -3.6 kg in the 80-mcg group (P<.05).
     Based on the results, the 60-mcg dose was selected for future studies of the device.
     The investigators noted that in the 60-mcg group, total cholesterol declined 3.1%, triglycerides dropped 9.9%, low-density lipoprotein cholesterol decreased by 5.2%, and high-density lipoprotein cholesterol rose by 0.5%. The drug also had a beneficial effect on blood pressure, with a reduction of 1.7 mmHg in systolic and 7.8 mmHg in diastolic blood pressure.
     Rosenstock said that the tolerability of the continuous infusion was “excellent, with minimal gastrointestinal side effects noted.”