Orlistat (Ro 18-0647), a lipase inhibitor, in the treatment of human obesity: a multiple dose study.
OBJECTIVE
To evaluate efficacy and tolerability of the lipase inhibitor Orlistat (Ro 18-0647) in doses of 10, 60 and 120 mg three times a day in addition to a mild hypocaloric diet containing 30% of calories as fat.


METHODS
4 week single-blind placebo run-in period of diet alone followed by a 12 week double-blind, placebo-controlled, randomized treatment period.


METHODS
Five European outpatient clinics specializing in endocrinology and/or the treatment of obesity, one central laboratory.


METHODS
Of 237 healthy obese subjects meeting the inclusion criteria, 188 showed compliance to the diet during the run-in period and were randomized for the treatment period.


METHODS
Primary efficacy criterion was the difference in weight loss after 12 weeks of treatment between the Orlistat treated groups and the diet alone group. Secondary efficacy criteria were changes in serum total, HDL- and LDL-cholesterol.


RESULTS
Compared to placebo a mean (+/- s.e.) additional weight loss of 0.63 +/- 0.54 kg with 30 mg a day (P = 0.246), 0.71 +/- 0.55 kg with 180 mg a day (P = 0.190) and 1.75 +/- 0.54 kg with 360 mg a day was seen (P = 0.001) or Orlistat was observed. Overall data indicated dose-dependency. Small decreases were seen in total and LDL-cholesterol (significant in the 180 and 360 mg a day groups) and LDL- to HDL-cholesterol ratio (significant in the 360 mg a day group only). Mild, mostly gastrointestinal side effects were observed more frequently in the Orlistat groups and caused premature withdrawal from the study in only four patients. No marked laboratory abnormalities were shown, including the lipid-soluble vitamins A, D and E.


CONCLUSIONS
Orlistat, in an apparently dose-dependent manner, leads to additional weight loss compared to diet alone and overall, is well tolerated.
Drent
M L
ML
Department of Endocrinology, Free University Hospital, Amsterdam, The Netherlands.
Larsson
I
I
William-Olsson
T
T
Quaade
F
F
Czubayko
F
F
von Bergmann
K
K
Strobel
W
W
Sjöström
L
L
van der Veen
E A
EA
D000328:Adult; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003718:Denmark / Q000453:epidemiology; D004038:Diet, Reducing / Q000592:standards; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007783:Lactones / Q000009:adverse effects / Q000592:standards / Q000627:therapeutic use*; D008049:Lipase / Q000037:antagonists & inhibitors*; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D009765:Obesity / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology; D000077403:Orlistat; D013548:Sweden / Q000453:epidemiology; D015431:Weight Loss / Q000187:drug effects / Q000502:physiology
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D007783:Lactones; D000077403:Orlistat; D008049:Lipase