Pharmacologic options for the treatment of obesity

Past and current drug therapies for weight loss are discussed. More than 50% of Americans can be categorized as overweight or obese. Obesi ty is associated with increased mortality and with comorbidities such as hy pertension, hyperglycemia, dyslipidemia, coronary artery disease, and certa in cancers. According to guidelines for identification, evaluation, and tre atment of obesity, patients with a body mass index (BMI) of greater than or equal to 30 kg/m(2) should attempt to lose weight. Patients with a BMI of greater than or equal to 25 kg/m(2) plus two or more risk factors or patien ts with an excessive waist circumference plus two or more risk factors shou ld also attempt to lose weight. The initial goal is a 10% weight reduction in six months achieved through lifestyle changes. if lifestyle changes alon e are not effective, then drug therapy may be indicated. Pharmacotherapeuti c options for obesity have decreased over the past few years. Fenfluramine, dexfenfluramine, and phenylpropanolamine have been withdrawn because of se vere adverse effects, leaving only sympathomimetics, sibutramine, and orlis tat as anorectics with FDA-approved labeling. Phentermine has been shown to cause a 5-15% weight loss if given daily or intermittently. Compared with sibutramine and orlistat, phentermine is cheaper, and specific formulations allow once-daily administration. However, phentermine is indicated only fo r short-term treatment, and tolerance often develops. Common adverse effect s associated with phentermine are dry mouth, insomnia, increased blood pres sure, and constipation. Sibutramine increases norepinephrine and serotonin levels in the CNS and should not be taken with many antidepressants because of the risk of increased norepinephrine and serotonin levels. Its use is a lso contraindicated in patients with cardiovascular disease. Orlistat is no t systemically absorbed: therefore, it does not cause the systemic adverse effects or drug interactions of phentermine and sibutramine. Orlistat has a cholesterol-lowering effect not seen with other diet medications. However, the three-times-daily administration and frequent gastrointestinal effects limit its use. Sibutramine, phentermine, and orlistat have both positive and negative prop erties. Choosing among the medications will depend on concurrent disease st ates and medications, ease of administration, and cost.