Dietary therapy for obesity is a failure and pharmacotherapy is the future: a point of view.

1. We confront an escalating epidemic of obesity. The precipitating factors are undoubtedly environmental and include increasingly immobilizing occupations and technologies and an abundance of food in many societies. This understanding has led to the view that the obesity epidemic is entirely environmental and that obesity should be treated primarily by behavioural (particularly dietary) therapy. That is, a prominent view is that common human obesity is an environmental disease and is not, like hypertension and hypercholesterolaemia, a complex, multifactorial disease resulting from the interaction of genetic and environmental variance. 2. In the first part of the present article, I argue that this view has obscured a strong genetic-biological contribution to body mass and adiposity in humans. This is supported by studies of adopted children and twins and by rare Mendelian forms of human obesity. 3. In the second part of the present article, I argue that behavioural therapy for maintenance of weight loss is, overall, a failure. The overwhelming majority of people who lose weight by dieting regain it in several years. Many have blamed this on patients' lack of will-power and discipline, but there is mounting evidence that biological mechanisms contribute substantially to relapse from weight loss during dietary therapy. These include a compensatory decrease in energy expenditure during dieting and compensatory adaptations that would be expected to increase appetite. 4. We live in an era of evidence-based medicine; the evidence does not support the efficacy of diet therapy for maintenance of weight loss in obesity. This has been true for decades, despite efforts to improve behavioural therapy. Despite what we want to happen, this will not likely improve, because the failure of diet therapy for the maintenance of weight loss in obesity is probably primarily biological, not behavioural. 5. In the third part of the article, I argue that drugs will increasingly dominate the treatment of obesity. We are in the midst of a revolution in understanding the biological regulation of appetite and metabolism that began with the pioneering discovery of leptin. In my judgement, this will lead inevitably to the development of safe, effective therapy for obesity. 6. This transformation from behavioural to pharmacological therapy proved true with hypertension and hypercholesterolaemia. Pharmacological therapy for hypertension and hypercholesterolaemia followed the discovery of the pathways regulating arterial pressure and cholesterol biosynthesis, respectively, and behavioural therapy for these diseases is now secondary. Despite the skepticism, I predict that the same transformation will occur in the treatment of obesity. This is not to argue against the need for environmental modification to slow the escalating epidemic of obesity, but it is to suggest that future effective treatment of common human obesity should recognize the limitations of dietary therapy for maintenance of weight loss and the promise of pharmacological therapy.