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J Diabetes Sci Technol. 2014 May;8(3):551-9. doi: 10.1177/1932296814524871. Epub 2014 Feb 27.

A single-blind, placebo-controlled, dose-ranging trial of oral hepatic-directed vesicle insulin add-on to oral antidiabetic treatment in patients with type 2 diabetes mellitus.

Author information

1
Diasome Pharmaceuticals, Inc, Cleveland, OH, USA blair@sdgpharma.com.
2
Diasome Pharmaceuticals, Inc, Cleveland, OH, USA.
3
Diabetes and Glandular Research Center, San Antonio, TX, USA.
4
Biopharmatech Consulting, Inc, Leesburg, VA, USA.

Abstract

The dose response of postprandial plasma glucose (PPG) to add-on, premeal oral hepatic-directed vesicle-insulin (HDV-I), an investigational lipid bio-nanoparticle hepatocyte-targeted insulin delivery system, was evaluated in a 3-test-meal/day model in type 2 diabetes patients. The single-blind, placebo-controlled, dose-escalating trial enrolled 6 patients with HbA(1c) 8.6 ± 2.0% (70.0 ± 21.9 mmol/mol) and on stable metformin therapy. Patients received oral HDV-I capsules daily 30 minutes before breakfast, lunch, and dinner as follows: placebo capsules, 0.05, 0.1, 0.2, and 0.4 U/kg on days 1, 2, 3, 4, and 5, respectively. Outcome measures were PPG and incremental PPG area under the concentration-time curve (AUC). All 4 doses of oral HDV-I statistically significantly lowered mean PPG (P ≤ .0110 each) and incremental PPG (P ≤ .0352 each) AUC compared to placebo. A linear dose response was not observed. The 0.05 U/kg dose was the minimum effective dose in the dosage range studied. Three adverse events unrelated to treatment were observed. Add-on oral HDV-I 0.05-0.4 U/kg significantly lowered PPG excursions and the dose response curve was flat. These results are consistent with the lack of a linear dose response between portal and systemic plasma insulin concentrations in previous animal and human studies. Oral HDV-I was safe and well tolerated.

KEYWORDS:

dose response; hepatic-directed vesicle insulin; insulin delivery system; oral; postprandial plasma glucose; type 2 diabetes

PMID:
24876619
PMCID:
PMC4455427
DOI:
10.1177/1932296814524871
[Indexed for MEDLINE]
Free PMC Article

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