Pharmacotherapy for Obesity: Past, Present and Future

The prevalence of obesity has rapidly increased in all industrialized countries in the past few decades, most likely due to dietary and lifestyle changes. Since 1980, the prevalence of obesity has increased threefold or more worldwide. Obesity is associated with a number of diseases and metabolic abnormalities, many of which have high morbidity and mortality rates. These diseases include type 2 diabetes, hypertension, dyslipidemia, coronary heart disease, gallbladder disease, and some cancers. Even relatively modest decreases in body-weight (5-10% of the initial body weight) lead to marked improvements in blood pressure, and sugar and lipid control in obese patients. Obesity treatment should begin with lifestyle changes that focus on behavioral modifications, diet control, and regular exercise. Pharmacotherapy provides an adjunct for obesity treatment, but should be used in conjunction with non-pharmacological approaches such as reduced caloric intake and increased exercise. The history of pharmacotherapy for obesity is no great success story because most anti-obesity drugs have been withdrawn from the market based on the US Food and Drug Administration warnings of serious adverse reactions. At present, only orlistat and sibutramine have been approved by the US Food and Drug Administration for long-term use, but sibutramine was withdrawn from sale in the European Union in January 2010. Rimonabant was approved for use in the European Union in 2006 but officially withdrawn in 2009. There are still many compounds under clinical development, including a new cannabinoid-1 receptor antagonist, a 5-HT2c receptor agonist, ghrelin receptor antagonists, and inhibitors of gastrointestinal lipases. All of these compounds are still in preclinical or early clinical development stages. It will take time to tell whether these compounds can be used as anti-obesity drugs in the near future.