GLP-1 tablet in type 2 diabetes in fasting and postprandial conditions.

Abstract:

OBJECTIVE:To examine the absorption of glucagon-like peptide (GLP)-1(7-36) amide from the buccal mucosa of type 2 diabetic patients. Previously, the effects of the peptide have been studied following intravenous and subcutaneous injection. Now, a mucoadhesive, biodegradable buccal GLP-1 tablet (9 mm) containing 119 nmol has been developed as a possible alternative to injection. RESEARCH DESIGN AND METHODS:A total of 10 type 2 diabetic patients received a single tablet under fasting conditions and before a standard meal in this randomized placebo-controlled study. RESULTS:The mean peak GLP-1 concentration was 125.1 pmol/l and occurred 30 min after application. The mean placebo-adjusted area under the curve was 5,334 min pmol/l, consistent with a relative bioavailability of 6% vs. intravenous injection and 42% vs. subcutaneous injection. The half-life of total peptide activity after buccal administration was 17 min. The placebo-adjusted glucose concentrations decreased by 1.4 mmol/l in fasting experiments and by 4.2 mmol/l after a standard mixed meal. In the fasting state at 30 min, plasma insulin increased by 185% and glucagon decreased by 20%, consistent with the increase in plasma GLP-1 concentrations. The peptide exerted a significant insulinotropic effect during meals (calculated as an insulinogenic index, 0-120 min; 84.1 vs. 45.7 in placebo experiments). CONCLUSIONS:Potentially therapeutic plasma levels of GLP-1 were achieved after administration of a single buccal tablet in type 2 diabetic patients. The peptide had a marked glucose-lowering effect during the first 2 h. This new GLP-1 tablet may become a feasible alternative treatment for type 2 diabetic patients, although a more prolonged pharmacokinetic profile is required.

journal_name

Diabetes Care

journal_title

Diabetes care

authors

Gutniak MK,Larsson H,Sanders SW,Juneskans O,Holst JJ,Ahrén B

doi

10.2337/diacare.20.12.1874

subject

Has Abstract

pub_date

1997-12-01 00:00:00

pages

1874-9

issue

12

eissn

0149-5992

issn

1935-5548

journal_volume

20

pub_type

临床试验,杂志文章,随机对照试验
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    journal_title:Diabetes care

    pub_type: 临床试验,杂志文章,随机对照试验

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    pub_type: 杂志文章,meta分析,评审

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    pub_type: 杂志文章

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    pub_type: 杂志文章

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