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.