Last December the Royal College of Physicians of London revised its recommendations for the use of drugs to enhance weight loss. The Health Survey for England 1996 had recently reported that 16% of men and 17% of women were obese – double the levels in 1980. Coupled with this was the rapid exit, led by the manufacturers, of the fenfluramine drugs following reports of severe side-effects, and the introduction in the UK of the pancreatic lipase inhibitor, orlistat (Xenical).
The Report1 focuses on the appropriate management of weight loss combined with control of risk factors, such as hypertension and diabetes. The importance of exercise and behavioural modification as well as dietary change is stressed. Diet should involve a lifelong change in habits. Change will usually be led by reduced intake of fats and refined carbohydrates, and increased intake of fresh fruit and vegetables. Typically, for the moderately active in middle age, this involves a daily intake of around 1500kcal for women and 1800kcal for men – an approximate deficit of 600kcal.
The Working Party recommends the use of drugs only to accelerate weight loss, or to maintain reduced weight in those fitting the obesity definition of BMI >=30, falling to 28 if there are other risk factors such as diabetes, hypertension or ischaemic heart disease.
A minimum of 3–6 months of supervised dietary care is the recommended first step. If 10% weight loss is achieved, encouragement to continue without drugs is advised. If this is not attained, orlistat may be considered if 2.5kg has been lost in the preceding month. After 12 weeks on orlistat, if weight has not fallen by 5% the patient is a non-responder and the drug should be stopped. If 5% loss is achieved the drug may be continued unless weight subsequently rises. The maximum limit on continuous use is 2 years.
Abdominal discomfort and fatty faeces 'leaking' per rectum are not infrequent side-effects. The other drug available in the UK is phentermine, which is only recommended for courses of 4–8 weeks to avoid dependency.
The Report cites just three trials as the basis for recommending this drug.2–4 It also points out that the experience of using anti-obesity drugs in randomised controlled trials lasting one year is that overall only 30% reach the objective of 10% weight loss, i.e.70% are inadequate responders. A further 2-year randomised controlled trial of orlistat has also reported. Weight loss in the actively treated group (mean ±2 SEM) was 8.76±0.37kg and 5.81±0.67kg in the placebo group in the first year. Weight regain in year two was 3.2±0.45kg in those continuing with the usual dose of orlistat and 5.63±0.42kg on placebo.5 These data show moderate benefits over 2 years.
Looked at in another way, over 2 years placebo and active drug led to respectively 4.5% and 7.6% average weight loss – a 3% difference. Given that the initial mean weight was 100kg in active and control groups, approximately 3kg weight loss cost £43.10/month, times 24 = £1034.40 over 2 years, or £344.80/kg. This is not cheap.
By intention, orlistat produces fat malabsorption. Falls in blood levels of fat-soluble vitamins are documented in trials5 and in the Xenical Summary of Product Characteristics. These are thought to be modest and the product's Datasheet advises that 'use of a multivitamin supplement could be considered'. Evidence suggests that fat-soluble vitamins may be important in protecting against vascular disease and various cancers. Some physicians will have reservations about inducing fat malabsorption in the absence of data from trials evaluating the effects on morbid events and mortality.
- Report of the Royal College of Physicians. Clinical management of overweight and obese patients with particular reference to the use of drugs. The Royal College of Physicians of London, 1998.
- James WPT, Avenell A, Broom J, Whitehead J. Int J Obes 1997; 21 (Suppl 3): S24-30.
- Drent MJ, Larsson I, Williams-Olsson T et al. Int J Obes 1995; 19: 221-6.
- Sjostrom L, Rissanen A, Anderson T et al. Lancet 1998; 352: 167-73.
- Davidson MH, Hauptman J, DiGirolamo M et al. JAMA 1999; 281 : 253-42.