Control of Postprandial Plasma Glucose by an Oral Insulin Product (HIM2) in Patients With Type 2 Diabetes
Authors: Kipnes Mark , Dandona Paresh , Tripathy Devjit , Still J. Gordon , Kosutic Gordana 
Published: March 2007

OBJECTIVE—The objectives of this exploratory study were to assess the postprandial glucose-lowering effects and evaluate the safety and tolerability of single, escalating doses of an oral insulin product, hexyl-insulin monoconjugate 2 (HIM2), in patients with type 2 diabetes. Subcutaneous insulin and oral placebo were also administered for comparison.

RESEARCH DESIGN AND METHODS—Eighteen patients with type 2 diabetes were enrolled in this randomized, single-blind, placebo-controlled, three-way crossover, dose-escalation study. A single dose of each of the following study drugs was administered to each patient on 3 separate days: oral HIM2 (at one of three dose levels: 0.375, 0.5, or 1.0 mg/kg), subcutaneous regular insulin (8 units Humulin R), and oral placebo. At 30 min after dosing, patients ingested a standardized test meal (16 oz/720 calories of Boost Plus). Serial blood samples were collected for determination of plasma glucose and insulin concentrations during the 4-h postdose period.

RESULTS—The mean glucose area under the curve for 0 to 240 min (AUC0–240) values were lower following administration of 0.5 and 1.0 mg/kg HIM2 vs. placebo (1,097.1 vs. 1,196.9 and 801.1 vs. 992.1 mg · h−1 · dl−1, respectively). This difference was statistically significant at the 1.0-mg/kg HIM2 dose level. Insulin exposure, as measured by insulin AUC0–240 values, for the 0.375-, 0.5-, and 1.0-mg/kg dose levels of HIM2 were 169.9, 193.1, and 230.8 μU · h−1 · ml−1, respectively; insulin AUC0–240 values for placebo were 165.8, 196.1, and 169.2 μU · h−1 · ml−1, respectively. The mean glucose AUC0–240 values were similar following administration of 0.5 and 1.0 mg/kg HIM2 vs. subcutaneous insulin (1,097.1 vs. 1,048.0 and 801.1 vs. 875.2 mg · h−1 · dl−1, respectively). For pooled data from the 0.5- and 1.0-mg/kg dose groups, the HIM2/subcutaneous insulin ratios for the 2-h postprandial glucose concentration (0.97, 95% CI 0.90–1.06), maximum postprandial glucose concentration (0.99, 95% CI 0.93–1.06), and glucose AUC0–240 (0.98, 95% CI 0.9–1.06) were within 10% of unity, implying glucodynamic equivalence. Although HIM2 (0.5 and 1.0 mg/kg) and subcutaneous insulin (8 units) provided comparable control of postprandial plasma glucose concentrations, HIM2 resulted in peripheral insulin concentrations that were lower than subcutaneous insulin (mean insulin AUC0–240 of 193.1 vs. 233.6 and 230.8 vs. 270.3 μU · h−1 · ml−1, respectively).

CONCLUSIONS—Single, oral doses of HIM2 were safe and well tolerated. HIM2 (0.5 and 1.0 mg/kg) was more effective than placebo and as effective as subcutaneous regular insulin (8 units) at controlling postprandial glycemia with respect to the following parameters: 2-h postprandial glucose concentration, maximum glucose concentration, and glucose AUC0–240. This occurred even though peripheral insulin concentrations were lower following the administration of HIM2 (0.5 and 1.0 mg/kg) than subcutaneous insulin. Thus, HIM2 therapy may control postprandial glycemia without causing peripheral hyperinsulinemia in patients with type 2 diabetes.