Study of the anti-obesity drug orlistat (Xenical)
- note: lipase inhibitors work to partially block fat absorption.
- researchers at Columbia University randomized 668 obese adults to take either 120 mg of orlistat or a placebo three times daily in addition to being placed on a weight-loss diet and attending classes and counseling sessions with a dietician.
- found that those participants who took orlistat lost more weight, regained less weight, and showed greater reductions in blood pressure, waist circumference, cholesterol levels, and insulin levels, compared to placebo recipients.
- side-effects associated with use of orlistat included gas, urgent need to defecate, increased defecation, and fecal incontinence.
- authors say the findings suggest that orlistat can be an effective compliment to an overall obesity management program.
The Food and Drug Administration (FDA) Endocrinology and Metabolic Drugs Advisory Committee recently approved the use of Orlistat, a novel weight loss medication that has been widely tested throughout Europe (see June 1997 OMR for story). Orlistat, manufactured by F. Hoffman-La Roche Ltd.1 of Switzerland, will bear the name of Xenical when it becomes available in the United States. Final approval was expected later this month, but Roche announced on August 28, that it withdrew its New Drug Application (NDA) with the FDA because of increased incidence of breast cancer in clinical trial participants. Roche said that it is convinced there is no link between orlistat and the breast cancer, and it plans to resubmit its application within the next few months.
Mode of action. Xenical differs from previously available weight loss medications in that it works non-systemically acting locally in the gastrointestinal tract. It is a synthetic derivative of lipostatin, a naturally occurring lipase inhibitor ("fat blocker") which binds to gastric and pancreatic lipase, two digestive enzymes. Xenical also inhibits other digestive enzymes, including some found outside the gastrointestinal tract. When orlistat is taken with fat-containing foods, the fat passes through the gastrointestinal tract unchanged, and the calories are not absorbed. Pancreatic lipase reacts with the orlistat to reduce the absorption of about 30 percent of dietary fat, resulting in a reduction of approximately 200 calories per day. 1
Studies on orlistat. Studies presented at the 8th European Congress on Obesity in Dublin, Ireland on June 19, 1997 compared one- and two-year trials of Xenical. The subjects ate a mildly reduced calorie diet with fat comprising about 30 percent of the total number of calories. The findings showed that the average patient in the study, weighing 220 pounds, lost 20 pounds, or about 10 percent of body weight, by taking Xenical. Additionally, most of the patients in the study maintained their weight loss. 2 Most importantly, life-risk factors were reduced such as LDL and total cholesterol, both systolic and diastolic blood pressure, and blood glucose levels. Improvement in insulin levels was also noted. The suggested dosage is 120 mg tid with meals. Commonly reported side effects include abdominal cramping and diarrhea, secondary to increased fat excretion in the feces. Since the decreased absorption of fat leads to concomitant malabsorption of the fat-soluble vitamins, A, D, E, & K, it is recommended that a multi-vitamin containing supplements of these vitamins be taken daily while undergoing Xenical administration. Also affected is the absorption of extremely lipophilic drugs.
