(February 2001)

Orlistat (trade name Xenical) is a drug that reduces fat absorption. In this two-year study published in the Journal of the American Medical Association in 1999, 657 patients were given the drug and 223 were untreated controls. The population was middle aged and overwhelmingly white and female. Their weight averaged about 220 pounds at the start of the study. Both groups were put on weight loss diets for the entire two years. After one year, those on Orlistat were divided into three groups: one received no additional drug, one continued on the drug at the original dose (120 milligrams, three times a day), and one received one-half the initial dose.

The group on diet alone lost about ten pounds over the two-year study period; but, during the second year, their weight was slowly creeping up. In the group that stopped Orlistat after one year, weight was about the same as the diet alone (no drugs) after two years; both lost about 4 percent of body weight. Those still on Orlistat plus diet showed the best results, a 7.6 percent reduction in body weight; but, despite taking the drug in full dose for two years, they were only seven or eight pounds lighter than the diet alone group.

Those on the full Orlistat dosage for two years showed a 6 percent drop in blood cholesterol levels.

The authors concluded: "two year treatment with Orlistat plus diet significantly promotes weight loss, lessens weight gain, and improves some obesity-related disease risk factors."

Commentary: The control group on diet alone lost a modest amount of weight; those taking the drug for two years lost almost twice that amount. Although average weight loss was 7.6 percent of initial body weight, 34 percent of those taking Orlistat for two years lost more than 10 percent of initial body weight; that is quite substantial. The principal side effects appeared to be intestinal bloating, oily stools, abdominal cramps, and other intestinal complaints. Because Orlistat-induced weight loss requires constantly taking the drug, it will be necessary to have a much longer follow-up period to make sure no serious side effects develop.

The authors claim that the drug improved heart disease risk factors such as blood cholesterol levels and blood pressure.

The blood pressure drop was unimpressive; the cholesterol level reduction of 6 percent was more impressive. The average blood pressure at the start was 119 systolic, 76 diastolic; that is quite normal. Blood cholesterol concentrations were on average 207 to 209 milligrams per deciliter at the start, minimally above the recommended 200 milligrams. Results from other studies indicate that any reduction in blood pressure results from the weight loss. On the other hand, Orlistat reduces blood cholesterol levels in two ways - as a result of weight loss and as a specific effect of the drug.

This is not the answer to the overweight problem in the United States. For the 35 percent of Americans who are moderately overweight (up to 20 percent over ideal weight), diet and exercise is still the most sensible approach, that is eating fewer calories and burning more calories. The danger of that degree of overweight is that a substantial percentage of moderately overweight persons develop abnormalities of blood pressure, cholesterol levels, or blood glucose levels. Weight loss can correct those defects - and it may only take loss of five to ten pounds. Another danger of modest overweight (up to 20 percent) is that it is easy to slip into the much more dangerous 20 percent or more overweight (that is frank obesity). If attempts at weight loss with diet and exercise do not succeed, adding Orlistat may help. For those who are really obese, the drug may be quite useful together with diet and exercise, but it is essential that those taking Orlistat adhere strictly to a diet with no more than 30 percent of calories from fat. That will increase the weight loss and reduce the intestinal side effects (bloating, diarrhea) from the Orlistat. One advantage to using Orlistat is that there is rapid feedback to the patient; take a meal full of fat while on Orlistat and you will soon suffer the consequences.

Davidson, M.H., et al. Weight control and risk factor reduction in obese subjects treated for 2 years with Orlistat: A randomized controlled trial. Journal of the American Medical Association. Vol 281. (January 20) Pgs 235-242. 1999.