Orlistat, an inhibitor of digestive lipases, is widely used for the treatment of
obesity. Previous reports on the effect of orally ingested
orlistat together with a meal on gastric emptying and secretion of gut
peptides that modulate postprandial responses are controversial. We investigated the effect of ingested
orlistat on gastric emptying and plasma responses of gut
peptides in response to a solid mixed meal with a moderate energy load. In healthy subjects, gastric emptying was determined using scintigraphy and studies were performed without and with 120 mg of
orlistat in pellet form in random order.
Orlistat shortened t lag and t half and decreased the area under the gastric emptying curve.
Orlistat significantly attenuated the secretion of
glucose-dependent insulinotropic
polypeptide (GIP) but did not alter the plasma responses of
cholecystokinin (CCK),
glucagon-like peptide-1 (GLP-1),
pancreatic polypeptide (PP), and
insulin. There was no
peptide YY (PYY) response. Area under the curve of gastric emptying was positively correlated with integrated secretion of GIP (r=0.786) in
orlistat and was negatively correlated with integrated plasma response of
GLP-1 (r=-0.75) in control experiments, implying that inhibition of fat absorption modifies determinants of gastric emptying of a meal.
Orlistat administered similar to its use in
obesity treatment accelerates gastric emptying of a solid mixed meal with a moderate energy load and profoundly attenuates release of GIP without appreciably altering plasma responses of CCK,
GLP-1, and PP. Since GIP is being implemented in the development of
obesity, its role in weight control attained by
orlistat awaits further investigation.