Introduction and Objective: In healthy individuals, GLP-1 receptors on vagal afferent nerve cells of the intestine play an important role in mediating the effects GLP-1. In this study a formulation capable of targeting the vagal afferents was employed to deliver semaglutide to intestinal GLP-1 receptors, to determine the duration of action after a single oral dose. Methods: Eight healthy subjects each received 4mg semaglutide formulated in Diabetology’s Axcess oral delivery formulation on day 0, preceded by a placebo two days before. An intravenous glucose tolerance test (IVGTT) was conducted two hours after administration. IVGTT were also conducted on days 1, 4 and 6 after administration of the active formulation. Efficacy was expressed as the difference in AUC (0-15 min) of insulin peak, and AUC (0-60 min) of glucose fall between day -2 and subsequent days. Results: Insulin levels increased above the placebo baseline on the day of administration, and every day thereafter, with a maximum of 25% increase seen on day 1 after administration (p = 0.025). Blood glucose levels fell below the baseline, with the greatest fall of 16% (p = 0.046) relative to placebo being observed on day 6. Blood levels sufficient to stimulate pancreatic GLP-1 receptors ( 100pmole/L) were also detected. Conclusion: Changes in insulin secretion and plasma glucose after IVGTT indicative of activity of semaglutide, lasted for six days after one dose of 4mg semaglutide administered in Diabetology's Axcess formulation. Disclosure R.R. New: None.
ROGER R.C. NEW (Fri,) studied this question.