Reactivating glyburide in a group of sulfonylurea tolerating and non-responding type 2 diabetics with the iso-oral insulin™ and isoglysulin™

Regular insulin bound to the oral ISOMED's drug delivery system has been designed to channel the bound insulin into the liver, just as that of the endogenously secreted insulin, where it induces the actions of insulin. In the Part-1 study, the efficacy, bioavailability and safety of ISO-glyburide (2 mg), oral insulin (32 U), and of glysulin™ (glyburide 2 mg, containing oral insulin 32 U) have been comparatively studied in a group of adult, non-insulin-dependent (type 2) diabetics who are not responding to a large oral doses of a sulfonylurea or phenformin type oral hypoglycemic agents. All studied diabetics were insulin antibody negative. In these groups of type 2 diabetics, ISO-glyburide reduced the blood sugar (BS) by 28 %, serum insulin (SI) was increased slightly to 45 μU/mL. The glysulin™ reduced BS more than 50 % (to 5 mmol/L; 112.5 mg/dL), the SI of 95 μU/mL and serum glyburide (SG) of 190 ng/mL. The SG level noticed after 10 mg of a commercial glyburide was 100-140 ng/mL with very little hypoglycemic effects in these type 2 diabetics. In 9 type 2 diabetics (8 males and 1 female) aged 45.6 ± 10.8 years old, an oral administration of insulin (32 U) reduced the BS from 11.1 mmol/L (249.8 mg/dL) to 5.5 mmol/L (123.8 mg/dL) with the corresponding elevation of SI from 19.6 μU/mL to 61.6 μU/mL. An oral dosing of glysulin™ not only produced a similar elevation of the SI as that of after an parenteral insulin, but also restored hypoglycemic activity of glyburide in those type 2 diabetics who were resistant to glyburide, therefore, significantly improved the management of sulfonylurea-resistant type 2 diabetics, who requires daily insulin injections. Some of these diabetics had been managed with rezulin, glucovacent (a combination of metformin and glyburide) which have caused liver toxicity, and lactic aci- dosis, respectively. In the part-II study, the oral insulin in the liquid form and as powder form in the capsules were compared among type 1, sulfonylurea-tolerating, and insulin-requiring type 2 diabetics, as well as in a healthy volunteer with normal blood glucose. After oral administration of the liquid form, the mean BS level was reduced from 9.6 mmol/L (216 mg/dL)to 5.5 mmol/L (123.8 mg/dL) at 1.8 hours. After the capsular form, the mean BS was reduced from 9 mmol/L (202.5 mg/dL) to 6.2 mmol/L (139.5 mg/dL) at 2.2 hours. The SI level was increased from 15.2 to 43.4 μU/mL at 2 hours after the capsular form, while it was increased from 14.6 to 100.6 μU/mL at 2 hours after the liquid form of oral insulin. After the oral insulin in the capsular and the liquid forms, the plasma C-peptide levels were not changed, suggesting that the orally administered oral insulin in the capsular and the liquid forms were bioavailable and effective in reducing the BS in those glyburide-resisting and insulin-requiring type 2, in the type 1, as well as in the non-diabetic, healthy normal volunteers. The oral insulin, and glysulin™ were effective and safe for the management of the type 2 diabetics who are not responding to relatively higher doses of sulfonylurea and requiring daily insulin injections to manage their diabetic conditions.