Oral modified insulin (HIM2) in patients with type 1 diabetes mellitus: Results from a phase I/II clinical trial

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.