Drug treatment of obesity in cardiovascular disease.

Obesity is a significant health problem worldwide and is associated with a number of co-morbidities including type 2 diabetes mellitus, hypertension, dyslipidemia, obstructive sleep apnea, and cardiovascular disease. A number of different pathophysiologic mechanisms including increased inflammation, oxidative stress, and insulin resistance have been associated with initiation and progression of atherosclerotic disease in obese individuals. Lifestyle modifications have provided modest results in weight reduction and the focus of interest has now shifted towards drug development to treat severely obese individuals with a body mass index (BMI) >30 kg/m(2) or those with a BMI >27 kg/m(2) who have additional co-morbidities. Different regimens focusing on dietary absorption or acting centrally to control hunger and food intake have been developed. However, their weight loss effect is, in most cases, modest and this effect is lost once the medication is discontinued. In addition, long-term use of these drugs is limited by significant side effects and lack of long-term safety and efficacy data. Orlistat is the only US FDA-approved medication for long-term use. A number of new medications are currently under investigation in phase III trials with promising preliminary results. This review comments on available anti-obesity pharmacologic regimens, their weight-loss benefit, and their impact on cardiovascular risk factors.