Oral administration of glucagon-like peptide 1 or peptide YY 3-36 affects food intake in healthy male subjects.
BACKGROUND
Peripheral infusion of glucagon-like peptide 1 (GLP-1) or peptide YY 3-36 (PYY3-36) reduces food intake in healthy, obese, and diabetic subjects. In vivo, both peptides are cosecreted from intestinal L cells; GLP-1 is subject to rapid breakdown by dipeptidyl peptidase IV, and together with PYY3-36 it is likely to be degraded in the liver before entering the systemic circulation. The largest concentrations are observed in the splanchnic blood rather than in the systemic circulation.


OBJECTIVE
In contrast with peripheral infusion, oral delivery of sodium N-[8-(2-hydroxybenzoyl) amino] caprylate (SNAC) mimics endogenous secretion. We aimed to investigate how this affects food intake.


METHODS
Twelve healthy male subjects were studied in a randomized, double-blind, placebo-controlled, 4-way crossover trial. Each subject received in random order 2.0 mg GLP-1, 1.0 mg PYY3-36, or 2.0 mg GLP-1 plus 1.0 mg PYY3-36; the peptides were mixed with SNAC. The placebo treatment was the delivery agent alone. Food intake during an ad libitum test meal was measured.


RESULTS
Both peptides were rapidly absorbed from the gut, leading to plasma concentrations several times higher than those in response to a normal meal. GLP-1 alone, but not PYY3-36, reduced total energy intake significantly, with marked effects on glucose homeostasis. Coadministration of both peptides reduced total energy intake by 21.5% and fullness at meal onset (P < 0.05) but not total 24-h energy intake.


CONCLUSIONS
The results show a marked effect of orally administered GLP-1 and PYY3-36 on appetite by showing enhanced fullness at meal onset and reduced energy intake. This trial was registered at clinicaltrials.gov as NCT00822705.
Steinert
Robert E
RE
Clinical Research Center, Department of Biomedicine, University Hospital, Basel, Switzerland.
Poller
Birk
B
Castelli
M Cristina
MC
Drewe
Juergen
J
Beglinger
Christoph
C
D000284:Administration, Oral; D000328:Adult; D004311:Double-Blind Method; D004435:Eating / Q000187:drug effects*; D004734:Energy Metabolism; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D006815:Hunger; D008297:Male; D010446:Peptide Fragments; D019894:Peptide YY / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D010919:Placebos; D012016:Reference Values; D012527:Satiation; D055815:Young Adult
D010446:Peptide Fragments; D010919:Placebos; D019894:Peptide YY; C061785:peptide YY (3-36); D052216:Glucagon-Like Peptide 1