A novel per-oral insulin formulation: proof of concept study in non-diabetic subjects.

ABSTRACT

AIMS: The aim of our study was to examine the absorption of insulin from the gastrointestinal (GI) tract, using a novel oral formulation-adding a delivery agent SNAC (sodium N-[8-(2-hydroxybenzoyl)amino] caprylate) in combination with insulin. METHODS: Capsules containing insulin and SNAC, in various combinations, were administered orally, as a single dose, to 12 non-diabetic subjects and four control subjects (receiving SNAC or insulin only) in order to assess its biological effect and safety. Plasma glucose levels, insulin and C-peptide concentrations, as well as SNAC levels, were determined, at timed intervals up to 4 h. RESULTS: In all cases, a glucose-lowering effect was demonstrated, preceded by an increase in plasma insulin levels. The nadir of plasma glucose levels appeared after 30-50 min, following the ingestion of the mixture. The plasma insulin levels were found to parallel the blood SNAC levels. Plasma C-peptide levels were suppressed by the lowered glucose levels achieved concurrent with the increasing amount of exogenous insulin absorbed, indicating that the secretion of endogenous hormone was partially abolished. There were no biological effects regarding blood glucose levels upon administration of SNAC or insulin when given alone. No adverse effects were detected during the trial or several weeks after the trial. CONCLUSIONS: Insulin in combination with a novel delivery agent, SNAC, given orally, is absorbed through the GI tract in a biologically active form. This was demonstrated by a glucose lowering effect of the mixture as well as a suppression of an endogenous insulin secretion.