Lipase inhibition: a novel concept in the treatment of obesity.
Orlistat (Ro 18-0647) is an inhibitor of gastric, carboxylester and pancreatic lipase and specifically reduces the absorption of dietary fat due to the inhibition of triglyceride hydrolysis. Orlistat can be used for the treatment of obesity. Of 52 healthy obese patients entering a four-week single-blind run-in period with diet (500 kcal-reduced, containing 30% of calories in the form of fat) and placebo three times a day, 44 patients showed compliance to the diet by reducing their body weight by 0.5-4 kg from screening. These patients were randomized for a 12-week double-blind, parallel group, placebo-controlled treatment period with diet and 50 mg Orlistat or placebo three times a day. Complete data were available for 39 patients, 20 on Orlistat (3 men, 17 women; mean weight 85.5 +/- 12.1 kg; mean body mass index 30.6 +/- 3.7 kg/m2) and 19 on placebo (3 men, 16 women; mean weight 81.9 +/- 7.9 kg; mean body mass index 30.0 +/- 2.6 kg/m2. Total weight loss after randomization was 4.3 +/- 3.4 kg in the Orlistat group and 2.1 +/- 2.8 kg in the placebo group (P = 0.025, analysis of variance with repeated measurements; 95% confidence interval for the weight loss difference 0.2-4.2 kg). Gastrointestinal side effects were seen in the Orlistat group, but in most patients the symptoms were mild or transient. One patient dropped out because of faecal incontinence. No effect was seen on vitamin A levels, but vitamin E levels became lower in the Orlistat group (P < 0.05, paired t test).(ABSTRACT TRUNCATED AT 250 WORDS)
Drent
M L
ML
Department of Endocrinology, Free University Hospital, Amsterdam, The Netherlands.
van der Veen
E A
EA
D000293:Adolescent; D000328:Adult; D015992:Body Mass Index; D017024:Chemotherapy, Adjuvant; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007783:Lactones / Q000627:therapeutic use*; D008049:Lipase / Q000037:antagonists & inhibitors*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000178:diet therapy / Q000188:drug therapy*; D000077403:Orlistat; D015431:Weight Loss / Q000187:drug effects
D007783:Lactones; D000077403:Orlistat; D008049:Lipase