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.

Design: 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.

Conclusion: 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.