Therapeutic approaches to obesity

Obesity in the United States has become a public health crisis, with one third of the US population having a body mass index ≥30 kg/m2. Given the profound impact of obesity on cardiovascular disease (CVD), studies of lifestyle modification, pharmacotherapy, and surgical interventions must be reappraised to better define the roles of these approaches in preventing cardiovascular events. Recent clinical trials have attempted to quell the debate over macronutrient composition versus caloric restriction in the dietary approach to weight loss. Our interpretation of these results is that caloric reduction and adherence to diets are of greater consequence than the particular dietary content for weight reduction. For cardiovascular risk factor modification, however, specific macronutrient composition of the diet may have additional impact outside weight loss, although the ultimate relationship between various dietary macronutrients and clinical cardiovascular outcomes is unclear. Although pharmacotherapy has been used for decades to treat obesity, there currently are limited options and recurrent cautionary tales; therefore, we use these agents sparingly. Sibutramine, one of only two medications approved by the US Food and Drug Administration for the long-term treatment of obesity, recently came under intense scrutiny because of a possible increase in cardiovascular events, and it now is contraindicated in patients with established CVD. Orlistat and its over-the-counter form, Alli (GlaxoSmithKline, Research Triangle Park, NC), can induce modest weight loss but frequently are not tolerated because of unpleasant gastrointestinal side effects. Fortunately, there are new medications in phase 3 clinical trials that hold promise as potential alternatives for obesity treatment. Finally, bariatric surgery for morbid obesity refractory to lifestyle interventions has become considerably more common. Surgery can effectively reduce body weight and treat cardiovascular risk factors, particularly diabetes, with acceptable complication rates and should be considered a viable option for appropriate patients. Ongoing clinical trials will clarify the impact of bariatric surgery on cardiovascular events and mortality, as well as the role of surgery as a treatment option that may be considered earlier than currently recommended.