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The role of new anti-obesity drug orlistat in general practice |
Mode of action
In May Australia will join many other developed countries in being able to offer people on prescription from their GP a new drug to assist patients to lose weight. The drug is called orlistat (Xenical) and it is the first of a new class of anti-obesity agents with a unique mode of action that targets dietary fat. Orlistat is an inhibitor of gastrointestinal lipases, which are required for the systemic absorption of dietary triglycerides. It selectively inhibits GI lipase activity and prevents the absorption of 30% of dietary fat thus producing some weight loss.
Side effects
Orlistat works best with a low fat diet. In fact if too much fat is absorbed it will pass through the bowel in excessive amounts and may produce side effects such as fatty/oily stools, increased defaecation, liquid stools, oily spotting, faecal urgency, faecal incontinence, flatus with or without discharge. The amount of fat that can be consumed a day before such side effects become a problem is about 67 grams. The daily recommended fat intake for a patient on a weight management program is about 30-40 grams per day. These side effects whilst taking this medication can provide a patient with a window of opportunity to become permanently accustomed to a lower fat diet. It is not often that a side effect of a drug is in one sense a benefit and totally preventable, so long as the recommended low fat diet is adhered to.
No systemic absorption is required to exert its therapeutic effect and it has negligible systemic absorption. Side effects in other systems are no greater than placebo. Fat soluble vitamins decrease over two years but remain in the normal reference range.
Indications
Orlistat is indicated for long term treatment of those who are significantly overweight (BMI >/=27) with other risk factors or obese (BMI >/= 30). It should be used in conjunction with a hypocaloric diet (ie. up to 2,000 kcal or 8,400 kilojoules) containing no more than 30% of calories as fat. The daily intake of fat should be distributed over three main meals.
Contraindications
There are a few contraindications mentioned in the prescribing information and they mainly relate to GIT disorders such as chronic malabsorption syndrome, cholestasis, pancreatic enzyme deficiencies and major enzyme deficiencies. Care must taken with patients who have psychiatric illness and patients with eating disorders who could seek to take the drug inappropriately and need to be dealt with sensitively.
Dosage
Orlistat is best administered in one 120 mgm capsule during or up to one hour after each meal. Higher doses have no added benefit - nor will they increase side effects if taken in higher than recommended doses. Because orlistat has been shown to reduce the absorption of some fat soluble vitamins and beta-carotene some consideration should be given to give a multivitamin supplement for long term use. However as mentioned the serum levels of these vitamins do not seem to fall below recommmended levels and the need for vitamin supplements is still open to research and debate.
How effective is it in the primary care setting?
A recent two year double blind placebo controlled US study published in Archives of Family Medicine, the first conducted in the primary care setting, emphasises the advantage of diet plus orlistat over dietary treatment alone (1).
Looking at 684 patients taking 120 mgm tds in the primary care setting the study showed a 7.9kgm loss after a year compared with 4.1 kgm on placebo. 50% of patients treated with orlistat lost 5% or more of their initial weight in one year compared with 30% of placebo and about 34% of patients in the orlistat group sustained weight loss of 5% or greater over two years compared with 24% in the placebo group.
Orlistat produced greater improvements than placebo in serum lipid levels and blood pressure and was well tolerated although treatment resulted in a higher incidence if GI events. The 684 patients randomised in the study initially weighed an average of about 100kgm and had a BMI of 36.
All patients were prescribed a reduced energy diet for the first year based on an energy intake of about 1,500 kcal (6,300 kilojoules) with less than 30% of fat. They were given educational videos and pamphlets about eating behaviour, but were not referred to a dietitian and their doctors were not expected to provide extensive counselling. They were also told to exercise by walking briskly for 20-30 minutes 3-5 times per week.
Although the weight loss results were modest this study demonstrates that medication can help control weight and lipids over two years without extensive nutrition, exercise training and behavioural treatment. The addition of more active treatment with counselling, psychosocial support and lifestyle modification may produce greater efficacy in some patients. The drug when released in Australia will come with a support program via a 1800 phone number with trained dietitians, exercise physiologists and psychologists plus written material and that may improve on the above results.
The current six month trial being done in the GP setting in Australia which has such a patient support system in place will test this theory.
Comments
Orlistat is an effective adjunct to dietary and exercise advice in the treatment of obesity and its associated co-morbidity in general practice. Whilst the amount of weight loss may be modest there is the additional benefit of improvement of risk factors with improved lipid profile, reduced systolic and diastolic blood pressure, improved fasting glucose and insulin levels, reduced HbA1C in type 2 diabetes, reduced waist circumference and visceral adipose tissue.The GI side effects are not a problem providing a low fat diet is adhered to.
How long a patient will need to stay on orlistat will depend on many factors. Those who can permanently modify their lifestyle after six months may be able to maintain the weight loss after stopping the drug. Others will need to stay on it for longer. Many will regain some of the lost weight. More research is needed to further define its long and short term efficacy in clinical practice.
As regards cost it will be seen by some to be an expensive drug at about $140 per month and this may preclude its use for some needy people. However, the cost needs to weighed up against the above mentioned benefits, the fact that it comes with a support program, as well as the possible reduction in use and therefore cost of other adjunctive risk factor medication.
It may be that whilst people are very willing to spend money on medication for treatment when sick they may be less inclined to spend money on medication for risk factor reduction. It will be interesting to see the effect of the manufacturer’s (Roche) advertising through the media to promote the importance of weight loss and encouragement to see a GP, which will begin in May. The resulting enquiries about this drug by patients are likely to be numerous. Roche is currently conducting a campaign to educate GPs and other health professionals before the drug arrives on the shelves of pharmacies.
Overseas experience has shown that patient demand for orlistat is high and GPs need to be aware of the uses of this drug in clinical practice and be prepared to answer questions from their patients. It needs to be emphasised that it it not a quick fix or wonder drug and should not be taken for appearance and slimness but only for weight loss that is needed for health risk factor reduction.
Andrew Binns has a special interest in the management of obesity and has been running GutBuster courses for three years. Over the last six months he has taken part in a large randomised, double blinded clinical trial set in general practices around Australia to study the role of orlistat in the treatment of obesity. The results will be published later this year.
Reference
(1) Orlistat in the Long Term Treatment of Obesity in Primary Care Settings: Archives of Family Medicine: 2000:9:160-167
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