Pharmacologic Options for the Treatment of Obesity

Abstract and Introduction

Past and current drug therapies for weight loss are discussed.

More than 50% of Americans can be categorized as overweight or obese. Obesity is associated with increased mortality and with comorbidities such as hypertension, hyperglycemia, dyslipidemia, coronary artery disease, and certain cancers. According to guidelines for identification, evaluation, and treatment of obesity, patients with a body mass index (BMI) of 30 kg/m² should attempt to lose weight. Patients with a BMI of 25 kg/m² plus two or more risk factors or patients with an excessive waist circumference plus two or more risk factors should also attempt to lose weight. The initial goal is a 10% weight reduction in six months achieved through lifestyle changes. If lifestyle changes alone are not effective, then drug therapy may be indicated. Pharmacotherapeutic options for obesity have decreased over the past few years. Fenfluramine, dexfenfluramine, and phenylpropanolamine have been withdrawn because of severe adverse effects, leaving only sympathomimetics, sibutramine, and orlistat as anorectics with FDA-approved labeling.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 for short-term treatment, and tolerance often develops. Common adverse effects associated with phentermine are dry mouth, insomnia, increased blood pressure, 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 also contraindicated in patients with cardiovascular disease. Orlistat is not 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 properties. Choosing among the medications will depend on concurrent disease states and medications, ease of administration, and cost.

Obesity is a chronic disease with an increasing prevalence world-wide.^[1,2,3,4,5] Reports in the United Kingdom have found a 15% increase in the overweight and obese population between the years of 1980 and 1992^[4] and within the past decade the prevalence has doubled.^[2] Similar increases have been observed in Sweden,^[6] the Netherlands,^[7] and other developed and developing countries.^[1] The United States is no exception to these troubling statistics. The National Heart, Lung, and Blood Institute reported that the percentage of obese people in the United States rose from 12.8% in 1976-80 to 22.5% in 1988-94, resulting in an estimated 97 million overweight adults.^[8] Other sources state that one of every three U.S. adults is overweight or obese.^{[9,10,11,12,13]} The most current data, released by the National Institutes of Health (NIH), state that more than 50% of Americans are overweight or obese, while 20% are obese as defined by a body mass index (BMI) of 30 kg/m² .^[8]

Obesity is associated with increased morbidity and mortality and is estimated to result in approximately 300,000 deaths yearly.^[12] Secondary comorbidities associated with this chronic disease include hypertension, heart disease, type 2 diabetes mellitus, dyslipidemia, stroke, gallbladder disease, osteoarthritis, sleep apnea, and breast, prostate, endometrium, and colon cancers.^[14] Although the exact relationship between obesity and hypertension is not known, estimates from population studies suggest that at least 75% of hypertension is directly associated with obesity.^[15] There is substantial evidence in the literature that blood pressure increases with weight gain, decreases with weight loss, and is responsible for the activation of the sympathetic nervous system, which can ultimately lead to changes in renal structure and function.^[8,15] Lipo-protein metabolism is also affected by obesity. Weight gain results in increased levels of triglycerides and low-density-lipoprotein (LDL) cholesterol and decreased levels of high-density-lipoprotein (HDL) cholesterol. Weight loss has the opposite effect on lipoprotein levels.^[8,15] Obesity has similar effects on insulin-receptor sensitivity in type 2 diabetes mellitus. More than 50% of the variance in insulin sensitivity is directly related to obesity.^[15] As weight increases, so does insulin resistance; with weight loss comes improved glycemic control.^[8,15,16,17]

The economic burden of obesity is substantial. A report published in 1994 estimated the cost of medical expenses and loss of income related to obesity in the United States to exceed $68 billion.^[18] In addition, more than $30 billion each year is spent on diet food, programs, and products to shed unwanted weight.^[19]

Am J Health Syst Pharm. 2001;58(14) © 2001 American Society of Health-System Pharmacists

Cite this: Pharmacologic Options for the Treatment of Obesity - Medscape - Jul 15, 2001.