Short-term intestinal lipase inhibition in normal-weight individuals does not affect postprandial peptide YY3-36 and glucagon-like peptide-1 levels, hunger or satiety.

Fat malabsorption associated with Roux-en-Y gastric bypass (RYGB) may contribute to elevated postprandial glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) after the procedure, leading to sustained weight loss and appetite reduction. This study investigated whether fat malabsorption via orlistat increases GLP-1 and PYY and if these increases would be proportional to changes in hunger and satiety. Five healthy participants received standardized meals with 120 mg orlistat or placebo in a randomized, double-blinded, crossover design for 3 days. On the final day, glucose, insulin, GLP-1, PYY3-36 and visual analogue scores for hunger and satiety were measured over a 14-hour period that included three meals. Fasting, 14-hour area under the curve (AUC) and meal-related AUC for glucose and insulin were similar, although postprandial increases in peak insulin and glucose were greater with orlistat. PYY3-36 , GLP-1, hunger and satiety were not different. In conclusion, short-term orlistat administration does not enhance postprandial GLP-1 or PYY3-36 or affect hunger or satiety in normal-weight individuals. Furthermore, fat malabsorption from RYGB is unlikely to mediate subsequent postprandial increases in GLP-1 and PYY.