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
| Autor: | John R. Lau, Theophilus J Gana, Len N. Rosenberg, Sherwyn Schwartz, W. Blair Geho |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Blood Glucose
Male medicine.medical_specialty Time Factors Endocrinology Diabetes and Metabolism medicine.medical_treatment Biomedical Engineering Administration Oral Capsules Bioengineering Type 2 diabetes Placebo Gastroenterology Internal medicine Internal Medicine medicine Humans Hypoglycemic Agents Insulin Single-Blind Method Adverse effect Glycated Hemoglobin business.industry Type 2 Diabetes Mellitus Original Articles Middle Aged medicine.disease Texas Metformin Dose–response relationship Treatment Outcome Endocrinology Postprandial Diabetes Mellitus Type 2 Area Under Curve Nanoparticles Drug Therapy Combination Female business Biomarkers medicine.drug |
| Zdroj: | Journal of Diabetes Science and Technology. 8:551-559 |
| ISSN: | 1932-2968 |
| DOI: | 10.1177/1932296814524871 |
| Popis: | Background: 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. Method: The single-blind, placebo-controlled, dose-escalating trial enrolled 6 patients with HbA1c 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). Results: 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. Conclusions: 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. |
| Databáze: | OpenAIRE |
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