Orlistat maintains biliary lipid composition and hepatobiliary function in obese subjects undergoing moderate weight loss.
OBJECTIVE
Orlistat, an intestinal lipase inhibitor, has recently been approved by the US Food and Drug Administration for treatment of obesity. The effects of orlistat on hepatobiliary function have not been previously defined. A 4 wk study was performed involving modest weight loss in obese subjects to observe any short-term hepatobiliary responses that occur after initiating treatment with orlistat and a hypocaloric diet.


METHODS
A total of 23 obese (BMI 30-41 kg/m2) subjects were randomized to a double blind t.i.d. treatment with 120 mg of orlistat or a placebo in conjunction with a hypocaloric diet (1200-1500 kcal/day). The study was designed to achieve similar modest weight loss in both groups in order to be able to directly assess the effects of orlistat. Cholesterol saturation, bile composition, and gallbladder motility were measured.


RESULTS
At the end of the treatment period, mean weight loss of 3.8 kg was achieved in the orlistat group (vs 2.3 kg with placebo, p = NS). Total bile acid concentration decreased significantly with placebo (-18.57 +/- 6.99 mmol/L; 95% CI = -32.26 to -4.87), but not with orlistat. Biliary phospholipid concentration decreased significantly with placebo (-4.38 +/- 1.91 mmol/L; 95% CI = -8.13 to -0.64) but not with orlistat. Mean changes from the baseline in cholesterol saturation index and gallbladder motility were similar in both groups. Microscopy of bile failed to reveal cholesterol microcrystals before or after treatment in either group.


CONCLUSIONS
Our findings indicate a primary initial effect of weight loss is a reduction in biliary bile acids and phospholipids. Orlistat blocks these adverse changes in biliary lipid composition and maintains hepatobiliary function. We speculate that the risk of formation of gallstones during weight loss may actually be lowered with orlistat.
Trouillot
T E
TE
University of Colorado Health Sciences Center, Denver 80262, USA.
Pace
D G
DG
McKinley
C
C
Cockey
L
L
Zhi
J
J
Häeussler
J
J
Guerciolini
R
R
Showalter
R
R
Everson
G T
GT
D000328:Adult; D019440:Anti-Obesity Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D001646:Bile / Q000737:chemistry*; D001647:Bile Acids and Salts / Q000737:chemistry; D002784:Cholesterol / Q000378:metabolism; D004311:Double-Blind Method; D002149:Energy Intake; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D005704:Gallbladder / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007783:Lactones / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D008049:Lipase / Q000037:antagonists & inhibitors; D008055:Lipids / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism; D000077403:Orlistat; D015431:Weight Loss
D019440:Anti-Obesity Agents; D001647:Bile Acids and Salts; D004791:Enzyme Inhibitors; D007783:Lactones; D008055:Lipids; D000077403:Orlistat; D002784:Cholesterol; D008049:Lipase