An effective, orally administered
insulin product would be of substantial benefit in the treatment of patients with
diabetes mellitus. This phase I/II clinical trial was the first to investigate the safety and effectiveness of a single oral dose of a modified human
insulin in controlling postprandial plasma
glucose levels in patients with
type 1 diabetes mellitus who were receiving basal continuous subcutaneous
insulin infusion (CSII)
therapy. Fourteen patients with
type 1 diabetes mellitus were evaluated in an open-label, 2-center, dose-escalation, nonrandomized study of oral
hexyl-insulin monoconjugate 2 (HIM2). After an overnight fast and prior to receiving a standardized meal (50%
carbohydrates, 30% fat, 20%
proteins; 650 calories), the patients received either no additional
insulin (day 1), or 0.5 to 1.0 mg/kg of HIM2 (day 2). All patients received a basal
insulin regimen by CSII throughout the study. Blood samples were collected for determination of
glucose and
insulin levels for 240 minutes post-dose. The postprandial
glucose excursion versus time curves showed clear reductions in
glucose values after both HIM2 doses (day 2) relative to no treatment (day 1), although the differences in the reductions were not statistically significant. When the data for both HIM2 doses were pooled, a statistically significant effect of HIM2 on
glucose excursion (as measured by AUCex(30-240)) was observed. Mean +/- SD values for AUCex(30-240) were 501.35 +/- 124.1 mg. h/dL after no treatment and 375.81 +/- 215.5 mg. h/dL after HIM2 (Wilcoxon signed-rank test, P =.042). The results of this study suggest that oral HIM2, when added to a basal
insulin regimen, was safe and may prove effective in controlling
postprandial hyperglycemia in patients with
type 1 diabetes mellitus. Further clinical investigation is necessary.