Orlistat is a pentanoic acid ester that binds to and inhibits gastric and pancreatic lipases; the resulting inhibition of their activity prevents the absorption of about 30% of dietary fat compared with a normal 5% loss. Weight loss is due to calorie loss but drug-related adverse effects also contribute by diminishing food intake. The drug is not absorbed from the alimentary tract.
Clinical trials show that patients who adhere to a low-calorie diet and take orlistat lost on average 9-10 kg after one year (compared to 6 kg in those who took placebo); in the following year those who remained on orlistat regained 1.5-3.0 kg (4-6 kg with placebo). Orlistat has found a place in the management of obesity in the UK but, not surprisingly, this is subject to stringent guidance from the National Institute for Clinical Excellence, namely that it be initiated only in individuals:
• with BMI28 kg/m2 or more who also have cardiovascular risk factors or 30 kg/m2 or more without such comorbidity and
• who have lost at least 2.5 kg body weight by dieting and increasing physical activity in the previous month.
The dose is 120 mg, taken immediately before, during or 1 h after each main meal, up to thrice daily. If a meal is missed, or contains no fat, the dose of orlistat should be omitted.
Treatment should be accompanied by counselling advice and proceed beyond 3 months only in those who have lost > 5% of their initial weight, beyond 6 months in those who have lost > 10%, should not normally exceed 1 year, and never more than 2 years.
Adverse effects include flatulence and liquid, oily stools, leading to faecal urgency, abdominal and rectal pain. Symptoms may be reduced by adhering to a reduced-fat diet. Low plasma concentrations of the fat-soluble vitamins A, D and E have been found. Orlistat is contraindicated where there is chronic intestinal malabsorption or cholestasis.
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