Review: Drug treatments for obesity: where are we heading and how do we get there?

Abstract

Obesity has reached epidemic proportions with an estimated 1.7 billion people worldwide classified as either overweight or obese. Obesity is associated with multiple co-morbidities (often clustered as the metabolic syndrome), and can result in decreased life expectancy, with enormous costs to society. Even modest weight loss has been demonstrated to exhibit beneficial effects on the co-morbidities of obesity. While reduced caloric intake and increased physical activity, combined with behavioural modification, appears to be the most rational approach to weight reduction, it only offers short-lived success. For severely obese individuals, bariatric surgery has become an increasingly preferred option resulting in dramatic and well-maintained weight reductions followed by significant changes in obesity-related diseases.

Currently, few anti-obesity drugs are approved by regulatory authorities for long-term use (i.e. orlistat, sibutramine and rimonabant). Anti-obesity drug development is an active and dynamic field focusing on two major approaches: 1) inhibiting energy intake by addressing the input into the hypothalamic feeding centre or, 2) attempting to accelerate energy expenditure. Overcoming the hurdles of developing such medications is a daunting task, but it can be anticipated that several drugs in current development might become available within the next decade, and combination therapy of two or more agents could be the future of pharmacological prevention and treatment of obesity.