Pharmacokinetics and pharmacodynamic effects of oral GLP-1 and PYY3-36: a proof-of-concept study in healthy subjects.
This proof-of-concept study was performed in order to establish the pharmacokinetics and pharmacodynamics of increasing oral doses of the satiety peptides glucagon-like peptide-1 (GLP-1) and peptide YY3-36 (PYY3-36). Six healthy male subjects were given oral doses of either a placebo or GLP-1 in a dose-escalating schedule (doses of 0.5, 1.0, 2.0, and 4.0 mg). Next, another group of six healthy male subjects were given oral doses of either a placebo or PYY3-36 in the same pattern of escalating doses (doses of 0.25, 0.5, 1.0, 2.0, and 4.0 mg). In healthy male volunteers, (i) oral administration of either of the peptides induced a rapid and dose-dependent increase in plasma drug concentrations; (ii) oral administration of GLP-1 induced a potent effect on insulin release; and (iii) both peptides suppressed ghrelin secretion. In conclusion, this study showed, for the first time, that satiety peptides such as GLP-1 and PYY3-36 can be orally delivered safely and effectively in humans.
Beglinger
C
C
Clinical Research Center, Department of Research, University Hospital, Basel, Switzerland. beglinger@tmr.ch
Poller
B
B
Arbit
E
E
Ganzoni
C
C
Gass
S
S
Gomez-Orellana
I
I
Drewe
J
J
D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D005240:Feasibility Studies; D054439:Ghrelin / Q000097:blood / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D008297:Male; D010446:Peptide Fragments; D019894:Peptide YY / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*
D054439:Ghrelin; D007328:Insulin; D010446:Peptide Fragments; D019894:Peptide YY; C061785:peptide YY (3-36); D052216:Glucagon-Like Peptide 1