Orlistat, a potent inhibitor of the pancreatic and intestinal lipases, is the first member of a new therapeutic class approved for the treatment of obesity. Its administration with fat-containing foods results in a partial inhibition of triglyceride hydrolysis in the digestive lumen and subsequent reduction of the free fatty acids and monoglycerides absorption. At the usual dosage of 120 mg tid, about 30% of ingested fat are excreted non digested in feces. When administered with a mildly hypocaloric diet, orlistat contributes to loss of weight by a additional caloric deficit and promotes further compliance of the obese patient to the dietary recommendations. Several double-blinded, placebo-controlled studies have shown a statistically significant loss of weight of about 10% when orlistat was prescribed with a well balanced, mildly hypocaloric diet to obese patients during one year. Moreover, small but significant beneficial changes in the serum lipid levels occurred in these patients. Because the orlistat molecule is not reabsorbed, its side effects are mostly due to the gastrointestinal effects and consist in steatorhea after fatty meals. However, the treatment is generally well tolerated. Since the recent withdrawal from the worldwide market of the anorectic agents, phentermine and fenfluramine, orlistat is at this time the only drug approved by the European Community for the treatment of obesity. However, its long-term value are not currently known.

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