title: GSK2374697, a long duration glucagon-like peptide-1 (GLP-1) receptor agonist, reduces postprandial circulating endogenous total GLP-1 and peptide YY in healthy subjects.
abstract: We investigated the effects of a long-duration glucagon-like peptide-1 (GLP-1) receptor agonist, GSK2374697, on postprandial endogenous total GLP-1 and peptide YY (PYY). Two cohorts of healthy subjects, one normal/overweight and one obese, were randomized to receive GSK2374697 2 mg (n = 8 each) or placebo (n = 4 and n = 2) subcutaneously on days 1, 4 and 7. Samples for plasma endogenous GLP-1 and PYY were collected after breakfast on days -1 and 12. Weighted mean area under the curve (0-4 h) of total GLP-1 and PYY in treated subjects was reduced compared with placebo. The least squares mean difference for change from baseline was -1.24 pmol/l [95% confidence interval (CI) -2.33, -0.16] and -4.47 pmol/l (95% CI -8.74, -0.20) for total GLP-1 and PYY, respectively, in normal/overweight subjects (p < 0.05 for both), and -1.56 (95% CI -2.95, -0.16) and -3.02 (95% CI -8.58, 2.55), respectively, in obese subjects (p < 0.05 for GLP-1). In healthy subjects, GSK2374697 reduced postprandial total GLP-1 and PYY levels, suggesting feedback suppression of enteroendocrine L-cell secretion of these peptides.
authors.affiliation: Grifols Therapeutics Inc, RTP, NC, USA.
authors.forename: J
authors.initials: J
authors.lastname: Lin
authors.affiliation: Discovery Medicine, GlaxoSmithKline Research and Development, Research Triangle Park, NC, USA.
authors.forename: R J
authors.initials: RJ
authors.lastname: Hodge
authors.affiliation: PAREXEL International, Durham, NC, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: O'Connor-Semmes
authors.affiliation: Discovery Medicine, GlaxoSmithKline Research and Development, Research Triangle Park, NC, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Nunez
mesh_terms: D000328:Adult; D000368:Aged; D062408:Breakfast; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000097:blood / Q000187:drug effects*; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D019894:Peptide YY / Q000097:blood / Q000187:drug effects*; D019518:Postprandial Period / Q000187:drug effects*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D055815:Young Adult
chemical_list: C000594852:GSK2374697; D011993:Recombinant Fusion Proteins; D019894:Peptide YY; D052216:Glucagon-Like Peptide 1
keywords: AlbudAb; GLP-1; GSK2374697; PYY; long-duration GLP-1 agonist