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Lipase inhibition by orlistat: effects on gall-bladder kinetics and cholecystokinin release in obesity
Article first published online: 19 FEB 2004
DOI: 10.1046/j.1365-2036.2004.01812.x
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How to Cite
Mathus-Vliegen, E. M. H., Van Ierland-Van Leeuwen, M. L. and Terpstra, A. (2004), Lipase inhibition by orlistat: effects on gall-bladder kinetics and cholecystokinin release in obesity. Alimentary Pharmacology & Therapeutics, 19: 601–611. doi: 10.1046/j.1365-2036.2004.01812.x
Publication History
- Issue published online: 19 FEB 2004
- Article first published online: 19 FEB 2004
- Accepted for publication 14 October 2003
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Summary
Background : Obese subjects are at risk of developing gallstones as a result of the obese state and during weight reduction.
Aim : 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 × 60 mg orlistat or 3 × 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.