Professor of Nutrition
Department of Endocrinology,
Metabolism and Nutrition
University Hospital Gasthuisberg
Obesity induces multiple metabolic characteristics that contribute to the pathogenesis of diabetes mellitus and cardiovascular diseases, and is associated with an increased morbidity and mortality risk. New and effective therapeutic tools are needed. It has recently been demonstrated that most obesity-related conditions significantly improve with a modest weight loss of 5–10%, even when the patient remains overweight.(2) It is important for the public to be told (and to believe) that diets are not just meant to be followed for five days or five months, but are meant to form the basis of every food choice throughout life. Healthy dietary habits are only one component of a general healthy lifestyle, which also includes physical activity and smoking cessation.
Effective weight control involves dietary therapy, physical activity, behaviour therapy, pharmacotherapy and surgery, alone and in combination. Setting achievable goals is crucial and should be a collaborative activity.
To assess the patient’s risk, obesity can be classified according to the body mass index (BMI = body weight [kg]/body height [m](2)) and waist circumference (see Table 1). Excess abdominal fat (especially visceral fat) is an important, independent risk factor for diseases like type 2 diabetes, hypertension and cardiovascular diseases.
Pharmacotherapy, approved for long-term treatment, can be a helpful adjunct for the treatment of obesity in some patients. However, drugs should be used only in the context of a treatment programme that includes diet, physical activity changes and behaviour therapy.
Sibutramine is a tertiary amine originally developed as an antidepressant but with weight loss-inducing properties (see Table 2). In most European countries, sibutramine will be (or is already) launched in 2001. Sibutramine acts centrally to block reuptake (but not release) of serotonin and noradrenaline released by hypothalamic neurons. This enhances satiety and reduces the fall in metabolic rate that occurs naturally with weight loss.
Clinical trials have shown that sibutramine can produce medically useful weight loss when accompanied by a comprehensive lifestyle support programme.(3) The STORM trial, an individualised management programme, showed weight loss in 77% of obese patients and sustained weight loss in most patients continuing therapy for two years. Additionally, changes in concentrations of high-density lipoprotein (HDL) cholesterol, very low-density lipoprotein (VLDL) cholesterol and triglycerides, but not low-density lipoprotein (LDL) cholesterol, exceed those expected from weight loss alone.(3)
Sibutramine is generally well tolerated in obese patients with type 2 diabetes, where weight loss is associated with improvements in metabolic control and quality of life.(4) It is also shown to be an effective and well-tolerated treatment for weight loss and weight maintenance in obese patients with controlled hypertension.(5)
Side-effects are generally mild, reversible and diminish over time. Dry mouth and insomnia are the most common. Small increases in heart rate can be expected with a limited increase in blood pressure if weight loss does not occur, so accurate monitoring of patients’ blood pressure is recommended – every two weeks for three months; monthly between month 4 and 6; and regularly thereafter at maximal intervals of three months. A randomised controlled trial is planned to demonstrate the long-term health benefits of weight management with sibutramine plus lifestyle interventions (diet and exercise). Primary outcome will be cardiovascular morbidity/mortality and progression to type 2 diabetes.
Orlistat is a non-systemically acting weight management agent that promotes and maintains weight loss by the partial inhibition (about 30%) of dietary fat absorption (see Table 2). Since its launch in 1998, there have been over 8.5m patients treated worldwide, and orlistat has been used extensively in clinical research programmes.
Orlistat taken with an appropriate diet promotes significantly more weight loss than placebo treatment after one year. During the second year of therapy, orlistat produced less weight regain than placebo.(6) Also, several obesity risk factors improved significantly more with orlistat treatment than with placebo.(6) In type 2 diabetes, orlistat improved glycaemic control, as reflected in significant decreases in HbA(1c), fasting glucose and in dosage reductions of oral sulphonylurea medication.(7) It also diminished the rate of progression to the development of impaired glucose tolerance and type 2 diabetes.(8)
The efficacy and safety of orlistat have been comprehensively studied. Because orlistat reduces dietary fat absorption, treatment can be associated with certain gastrointestinal events, such as oily stools. In general these effects are mild and transient. It has been suggested that these effects actually encourage patients to reduce the fat content of their food and adapt a healthier eating pattern. Data from up to two years of treatment are available; a number of studies are currently investigating the use of orlistat for three years and more. Data on the use of orlistat in children will be available in the near future.
Obesity is a serious problem for most industrialised countries. Although theoretically very simple, in practice the results of most treatment programmes are disappointing. It is clear that a multidisciplinary programme, including diet, physical activity and behaviour therapy, is crucial for success. For some patients, pharmacotherapy can be a helpful adjunct. Whatever the programme, patients need continued support and encouragement for the period of weight loss and, perhaps even more importantly, the period of weight maintenance. One of the best predictors of success is frequency of professional contact. Accurate weighing and measurement of waist circumference provides a positive contact.
- Serdula MK, Mohdad AK, Williamson DF, et al. Prevalence of attempting weight loss and strategies for controlling weight. JAMA 1999;282:1353-8.
- National Institutes of Health, National Heart, Lung and Blood Institute. Obesity Education Initiative. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults. Obes Res 1998; 6 Suppl 2: 51-210S.
- James WPT, Astrup A, Finer N, et al, for the STORM Study Group. Effect of sibutramine on weight maintenance after weight loss: a randomised trial. Lancet 2000;356:2119-25.
- Fujioka K, Seaton TB, Rowe E, et al. Weight loss with sibutramine improves glycaemic control and other metabolic parameters in obese patients with type 2 diabetes mellitus. Diabetes Obes Metab 2000;2:175-87.
- Hazenberg BP. Randomized, double-blind, placebo-controlled multicenter study of sibutramine in hypertensive patients. Cardiology 2000;94:152-8.
- Rössner S, Sjöström L, Noack R, et al, on behalf of the European Orlistat Obesity Study Group. Weight loss, weight maintenance, and improved cardiovascular risk factors after 2 years treatment with orlistat for obesity. Obes Res 2000;8:49-61.
- Hollander PA, Elbein SC, Hirsch IB, et al. Role of orlistat in the treatment of obese patients with type 2 diabetes. A 1-year randomised double-blind study. Diabetes Care 1998;21:1288-94.
- Heymsfield SB, Segal KR, Hauptman J, et al. Effects of weight loss with orlistat on glucose tolerance and progression of type 2 diabetes in obese adults. Arch Intern Med 2000;160:1321-6.
- McMahon RG, Fujioka K, Singh BN, et al. Efficacy and safety of sibutramine in obese white and African- American patients with hypertension. A 1-year, double-blind, placebo-controlled multicenter trial. Arch Intern Med 2000;160:2185-91.
European Childhood Obesity Group
European Society of Cardiology
European Association for the Study of Diabetes
Results of long-term trials with both sibutramine and orlistat will become available
The use of orlistat in children is also under evaluation
The search for the “best” drug in the treatment of obesity continues
23–25 May 2002
European Childhood Obesity Group Meeting
24–29 Aug 2002
9th International Congress on Obesity