Orlistat (marketed as Xenical by Roche) is a drug designed to treat obesity. Its primary function is to prevent the absorption of dietary fats, thereby reducing caloric intake. It is intended for use in conjunction with a physician-supervised reduced calorie diet.
Pharmacology
Orlistat works by inhibiting pancreatic lipase, an enzyme that breaks down triglycerides in the intestine. Without this enzyme, triglycerides from the diet are prevented from being hydrolyzed into absorbable free fatty acids and are excreted undigested. Only trace amounts of orlistat are absorbed systemically, the primary effect is local lipase inhibition within the GI tract after an oral dose. The primary route of elimination is through the feces.
At the standard prescription dose of 120 mg three times daily before meals, orlistat prevents approximately 30% of dietary fat from being absorbed.
Efficacy
The amount of weight loss achieved with orlistat is variable. In 1 year clinical trials, between 35.5% and 54.8% of subjects achieved a 5% or greater decrease in body mass. Between 16.4% and 24.8% achieved at least a 10% decrease in body mass. A significant amount of subjects regained the weight after they stopped using orlistat. Despite this cosmetically small effect, there was a 37% reduction in the incidence of Type 2 diabetes, a significant difference.
Side effects
The primary side effects of the drug are GI-related. Side effects were most severe within the first year of therapy. Because its main effect is to prevent dietary fat from being absorbed, the fat is excreted unchanged in the feces and so the stool may become oily or loose. Increased flatulence is also common. Bowel movements may become frequent or urgent. Rare occurrence of fecal incontinence have been seen in clinical trials. To minimize these effects, foods with high fat content should be avoided.
The absorption of fat-soluble vitamins are inhibited by the use of orlistat. A multivitamin tablet containing these vitamins (D, E, A and beta-carotene) should be taken once a day, at least 2 hours before or after taking the drug .
Concern was raised by the FDA regarding a possible link between Orlistat and breast cancer after reviewing a clinical trial in which 1016 women were given Orlistat, with ten of these patients later going on to develop breast cancer. Only one woman from the placebo group, containing 579 patients, suffered this complication. Roughly a four to seven fold increase in the probability of developing breast cancer as a result of Orlistat use has been suggested.
More recent reviews have addressed a connection Orlistat shares with aberrant crypt foci (ACF) in the colon, which is believed to be one of the earliest precursors of colon cancer
Contraindications
Xenical is contraindicated in:
§ Malabsorption
§ Reduced gallbladder function (e.g. after cholecystectomy)
§ Pregnancy and breastfeeding
§ Certain kidney problems