Reduction of postprandial blood glucose excursions by an optimised formulation of oral insulin

Background and Aims: Oral Insulin (OI) formulated with Emisphere's Eligen technology has been shown to exhibit a blood glucose lowering effect with a rapid onset of action. This makes OI attractive for prandial insulin therapy, however, the effect of OI is blunted when administered together with food. The aim of this pilot study was to identify an insulin/carrier-ratio optimised for pre-prandial administration of OI.

Methods: In a first subset of experiments, eight subjects with diet-treated Type 2 diabetes (age 56±6 years (mean±SD), BMI 29±4kg/m², HbA1c 6.7±0.7%) received single-dose administrations of two different formulations of OI (formulation A: 4 tablets, each 75 IU insulin + 100mg carrier, formulation B: 2 tablets, each 150 IU insulin + 80mg carrier). Both formulations led to a substantial decrease of fasting blood glucose, but formulation B had a stronger metabolic effect (maximum BG decrease -26±21 vs. -37±27mg/dl). Therefore, formulation B was used in a second series of experiments performed in a single-blind cross-over design in a subgroup of 4 patients. In these subjects, formulation B was administered together with a mixed meal (441 kcal, 66% carbohydrates). Blood glucose and insulin excursions were followed for 4 hours and compared with the results obtained with a control formulation which consisted of the carrier only.

Results: In comparison to the control formulation insulin concentrations rose faster with OI with significantly higher values early after drug administration (timepoint 25min: 55.0±19.5 (OI) vs. 27.7±13.1µU/ml (control), p<0.05). In accordance, blood glucose was lower with OI from 50min onwards (e.g., timepoint 120min: 147±27 (OI) vs. 169±33mg/dl (control)).

Conclusion: These promising effects of oral insulin on postprandial blood glucose and insulin excursions warrant further investigation of this optimised oral insulin formulation in larger trials.