Orally administered glucagon-like peptide-1 affects glucose homeostasis following an oral glucose tolerance test in healthy male subjects.
Glucagon-like peptide-1 (GLP-1) exerts several effects on glucose homeostasis and reduces food intake. After its release from intestinal L cells, GLP-1 is subject to (i) rapid breakdown by dipeptidyl peptidase IV and (ii) high liver extraction. The highest concentrations of GLP-1 are found in the splanchnic blood rather than in the systemic circulation. An oral delivery system would mimic endogenous secretion. Here we investigated the pharmacokinetic/pharmacodynamic (PK/PD) effects of a single dose (2 mg) of oral GLP-1 administered prior to an oral glucose tolerance test (OGTT) in 16 healthy males. GLP-1 was rapidly absorbed from the gut, leading to tenfold higher plasma concentrations compared with controls. The PD profile was consistent with reported pharmacology; GLP-1 significantly stimulated basal insulin release (P < 0.027), with marked effects on glucose levels. The postprandial glucose peak was delayed with GLP-1, suggesting an effect on gastric emptying.
Steinert
R E
RE
Clinical Research Center, Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
Poller
B
B
Castelli
M C
MC
Friedman
K
K
Huber
A R
AR
Drewe
J
J
Beglinger
C
C
D000284:Administration, Oral; D000328:Adult; D001066:Appetite / Q000187:drug effects; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D002210:Caprylates / Q000737:chemistry; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004337:Drug Carriers; D005746:Gastric Emptying / Q000187:drug effects; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D005951:Glucose Tolerance Test; D006706:Homeostasis; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D054795:Incretins / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D007328:Insulin / Q000097:blood; D007408:Intestinal Absorption; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D019518:Postprandial Period; D012016:Reference Values; D055815:Young Adult
D001786:Blood Glucose; D002210:Caprylates; D004337:Drug Carriers; D054795:Incretins; D007328:Insulin; C111140:N-(8-(2-hydroxybenzoyl)amino)caprylate; D010446:Peptide Fragments; C055453:glucagon-like peptide 1 (7-36)amide; D019382:Human Growth Hormone; D052216:Glucagon-Like Peptide 1; D005934:Glucagon