GSK-2374697

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.