OBESITY MANAGEMENT

In recent years increasing weight has become a problem in the populations of most countries with developed economies, including the United Kingdom. The main causes are increased consumption of energy-dense foods high in fats and sugars and reduced physical activity resulting from changes in lifestyle. The risks to health of overweight or obesity include cardiovascular disease, type 2 diabetes, some cancers, infertility, and arthritic conditions resulting from increased strain on bones and joints. Overweight and obesity are measured in terms of body mass index (BMI), calculated as weight (in kg) in relation to height (in metres) squared; waist circumference is also taken into account. A person is classed as overweight and at increased risk to health if the BMI is greater than 25 and waist measurement 94cm (38in) or more for men and 80cm (32in) or more for women. Obesity carries a substantially increased risk to health and is defined as a BMI greater than 30, with a waist measurement of 102cm (41in) or more for men and 88cm (35in) for women. Weight reduction is achieved through reduction in calorific intake, particularly saturated fats and high glycaemic index carbohydrates, combined with increased physical activity, which is simple but not necessarily easily achieved.

Orlistat (alli capsules, GSK Consumer Healthcare)

Orlistat (Xenical, Roche) was launched in 1998 as a prescription only anti-obesity agent. In May 2009 it became the first drug to be licensed by the European Medicines Agency (EMEA) as a non-prescription medicine throughout the European Union.

Mode of action

Orlistat is a specific, long-acting inhibitor of gastro-intestinal lipases. It exerts its therapeutic activity in the lumen of the stomach and small intestine by forming a covalent bond with the active serine site of the gastric and pancreatic lipases. The inactivated enzyme is thus unavailable to hydrolyse dietary fat, in the form of triglycerides, into absorbable free fatty acids and monoglycerides.

Uses

alli is licensed, in conjunction with a mildly hypocaloric diet, for the treatment of overweight patients (BMI > 28) aged 18 years or over.

Side-effects and cautions

Intestinal side-effects are common, including abdominal pain or discomfort, oily spotting from the rectum, flatus with discharge, faecal urgency, fatty or oily stools, flatulence, liquid stools and increased defecation. These increase if the diet is high in fat. Severe diarrhoea is also possible; this may reduce oral contraceptive efficacy and additional precautions should be taken in these circumstances.

Interactions

Orlistat possibly reduces the absorption of ciclosporin and concomitant use is not recommended. Caution should also be exercised when orlistat is used with acarbose, oral anticoagulants, fat soluble vitamins and amiodarone, because of possible interference with their absorption. The manufacturer also advises that patients taking multivitamins should take them at bedtime, presumably to allow for the longest period between meals for the absorption of fat-soluble vitamins, as the level of fats available in the intestine is reduced by orlistat.

Dose

The recommended dose is one 60mg capsule (half the strength of its prescription-only equivalent) immediately before, during or up to one hour after each main meal. If a meal is missed or contains no fat, the dose should be omitted. A dose results in increased faecal fat within 24 to 48 hours. When therapy is discontinued, faecal fat content usually returns to pre-treatment levels within 48 to 72 hours. Accompanying diet should be nutritionally balanced and mildly hypocaloric, containing about 30 per cent of calories from fat. alli may be used for up to six months, but patients should be referred to a doctor if there is no weight loss within 12 weeks.

Efficacy

Systematic reviews of clinical trials on prescription strength orlistat have found it superior to placebo.^1,2 A Cochrane Review found that, compared with placebo, orlistat-treated patients lost 2.9 per cent more weight and the number of patients achieving 10 per cent or greater weight loss was 12 per cent higher. Attrition rates averaged 33 per cent during the orlistat trials.³ Thus far, no clinical trials appear to have been published on non-prescription strength orlistat. However, GSK Consumer Healthcare claims that alli reduces the absorption of dietary fats by around 25 per cent, and that combining it with a reduced-calorie, low-fat diet can help patients lose 50 per cent more weight than dieting alone. The company claims that, in clinical studies, alli demonstrated comparable efficacy and safety profiles to Xenical, but had a lower incidence of treatment effects, and a lower percentage of trial subjects (3.2 per cent) withdrew due to gastro-intestinal side-effects compared with Xenical (5.4 per cent).

REFERENCES

1. Leung WY, Thomas GN, Chan JC, Tomlinson B. Weight management and current options in pharmacotherapy: orlistat and sibutramine. Clin Ther. 2003; 25:58-80.

2. Neovius M, Johansson K, Rössner S. Head-to-head studies evaluating efficacy of pharmaco-therapy for obesity: a systematic review and meta-analysis. Obes Rev. 2008; 9:420-7.

3. Padwal R, Li SK, Lau DC. Long-term pharmacotherapy for obesity and overweight. Cochrane Database Syst Rev. 2003; (4):CD004094.