Lipase inhibition by orlistat: effects on gall-bladder kinetics and cholecystokinin release in obesity.
BACKGROUND
Obese subjects are at risk of developing gallstones as a result of the obese state and during weight reduction.


OBJECTIVE
To study whether orlistat, by lipase inhibition, impairs gall-bladder emptying, thus further predisposing weight-losing obese subjects to gallstone formation.


METHODS
Patients entering a randomized clinical trial of 1 month of diet, followed by treatment with placebo, 3 x 60 mg orlistat or 3 x 120 mg orlistat, underwent gall-bladder emptying studies measured by ultrasound. Meal-induced cholecystokinin release and gall-bladder emptying were investigated at the start, at randomization and after 1 and 12 months.


RESULTS
One month of dieting did not change gall-bladder emptying and cholecystokinin release. After 1 month, placebo treatment resulted in a decreased fasting volume of 11%, compared with increases of 26% and 47% with 60 and 120 mg orlistat, respectively. Gall-bladder emptying increased by 9% with placebo and decreased by 15% and 53% with 60 and 120 mg orlistat, respectively. Fasting cholecystokinin values and cholecystokinin release decreased significantly in the orlistat group. After 1 year, a persistent but attenuated effect of orlistat on gall-bladder emptying and cholecystokinin release remained. Three of 40 patients developed gallstones, two on placebo with major weight loss and one on 60 mg orlistat.


CONCLUSIONS
One month of lipase inhibition by orlistat significantly impaired gall-bladder motility, which persisted to some extent after 1 year. Obese subjects with diabetes or hyperlipidaemia, who are more at risk of gallstones, should be followed carefully.
Mathus-Vliegen
E M H
EM
Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands. e.mathus-vliegen@amc.uva.nl
Van Ierland-Van Leeuwen
M L
ML
Terpstra
A
A
D000328:Adult; D019440:Anti-Obesity Agents / Q000627:therapeutic use*; D001835:Body Weight; D002766:Cholecystokinin / Q000378:metabolism*; D005260:Female; D005704:Gallbladder / Q000378:metabolism*; D006801:Humans; D007783:Lactones / Q000627:therapeutic use*; D008049:Lipase / Q000037:antagonists & inhibitors*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism; D000077403:Orlistat; D015431:Weight Loss
D019440:Anti-Obesity Agents; D007783:Lactones; D002766:Cholecystokinin; D000077403:Orlistat; D008049:Lipase