Control of postprandial plasma glucose by an oral insulin product (HIM2) in patients with type 2 diabetes

Mark Kipnes, Paresh Dandona, Devjit Tripathy, J. Gordon Still, Gordana Kosutic

Research output: Contribution to journalArticle

90 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)421-426
Number of pages6
JournalDiabetes Care
Volume26
Issue number2
DOIs
StatePublished - Feb 1 2003
Externally publishedYes

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Type 2 Diabetes Mellitus
Insulin
Glucose
Placebos
hexyl-insulin monoconjugate 2
Insulin, Regular, Human
Hyperinsulinism
Area Under Curve
Meals
Research Design

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Control of postprandial plasma glucose by an oral insulin product (HIM2) in patients with type 2 diabetes. / Kipnes, Mark; Dandona, Paresh; Tripathy, Devjit; Still, J. Gordon; Kosutic, Gordana.

In: Diabetes Care, Vol. 26, No. 2, 01.02.2003, p. 421-426.

Research output: Contribution to journalArticle

Kipnes, Mark ; Dandona, Paresh ; Tripathy, Devjit ; Still, J. Gordon ; Kosutic, Gordana. / Control of postprandial plasma glucose by an oral insulin product (HIM2) in patients with type 2 diabetes. In: Diabetes Care. 2003 ; Vol. 26, No. 2. pp. 421-426.
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abstract = "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.",
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T1 - Control of postprandial plasma glucose by an oral insulin product (HIM2) in patients with type 2 diabetes

AU - Kipnes, Mark

AU - Dandona, Paresh

AU - Tripathy, Devjit

AU - Still, J. Gordon

AU - Kosutic, Gordana

PY - 2003/2/1

Y1 - 2003/2/1

N2 - 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.

AB - 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.

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