Therapeutic options for modifying cardiometabolic risk factors.

Excessive adipose tissue is associated with increased expression or suppression of cytokines and hormones, leading to inflammation and chronic disease. In particular, abdominal adiposity, as evidenced by a high waist circumference, is a component of the metabolic syndrome, a constellation of risk factors (e.g., high waist circumference, high blood pressure, elevated triglycerides, low high-density lipoprotein cholesterol, elevated fasting glucose) that increases the risk for type 2 diabetes and cardiovascular disease. Lifestyle modification is the first-line approach to the management of obesity and the metabolic syndrome. However, for patients who cannot achieve a reduction in weight (5% to 10% of initial body weight) and cardiometabolic risk factors with lifestyle modification alone, physicians should consider adjunctive long-term pharmacotherapy. A variety of approved and investigational pharmacologic agents have been shown to reduce weight and modify metabolic syndrome components, including sibutramine, orlistat, metformin, and rimonabant. Data from four phase 3 trials suggest that rimonabant, the first cannabinoid receptor inhibitor, modulates cardiometabolic risk factors, both through its impact on body weight and through direct pathways that are not related to weight loss.