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Am Fam Physician. 2002;66(7):1279-1280

Questions Addressed

  • What are the effects of drug treatments for obesity in adults?

Trade off between benefits and harms
Unknown effectiveness
Sibutramine plus orlistat
Likely to be ineffective or harmful
Fenfluramine plus phentermine
To be covered in subsequent issues ofClinical Evidence
Ephedrine-caffeine, olestra, acarbose, cholecystokinin agonists, neuropeptide Y antagonists, beta3-adrenergic agonists, leptin, growth hormone, surgery
DefinitionObesity is a chronic condition characterized by an excess of body fat. It is most often defined by the body mass index (BMI), a mathematical formula that is highly correlated with body fat. BMI is weight in kilograms divided by height in meters squared (kg per m2). People with a BMI between 25 and 30 kg per m2 are categorized as overweight, and those with a BMI greater than 30 kg per m2 are categorized as obese.1
Incidence/PrevalenceObesity has increased steadily in many countries since 1900.2 In the past decade, the prevalence of obesity in the United States has increased from 12 percent in 1991 to 17.9 percent in 1998.3
Etiology/Risk FactorsThe etiology of obesity includes genetic and environmental factors. Obesity may also be induced by drugs (e.g., high-dose glucocorticoids), or be secondary to a variety of neuroendocrine disorders such as Cushing's syndrome and polycystic ovary syndrome.4
PrognosisObesity is a risk factor for several chronic diseases, including hypertension, dyslipidemia, diabetes, cardiovascular disease, sleep apnea, osteoarthritis, and some cancers.1 The relation between increasing body weight and the mortality rate is curvilinear, with mortality rate increasing in people with low body weight. Whether this is caused by increased mortality risk at low body weights or by unintentional weight loss is not clear.5 Results from five prospective cohort studies and 1991 national statistics suggest that the number of annual deaths attributable to obesity among U.S. adults is about 280,000.6
Clinical AimsTo achieve realistic gradual weight loss and prevent the morbidity and mortality associated with obesity, without undue adverse effects.
Clinical OutcomesWe found no studies that used the primary outcomes of functional morbidity or mortality. Proxy measures include mean weight loss (kg), number of people losing 5 percent or more of baseline body weight, and number of people maintaining weight loss.

Drug Treatments


We found good evidence from systematic reviews and subsequent randomized controlled trials (RCTs) that sibutramine is more effective than placebo for promoting modest weight loss in healthy, diabetic, and hypertensive obese adults (BMI 25 to 40 kg per m2). Weight regain occurs after stopping treatment. We found no evidence about safety beyond two years of treatment. Limited evidence suggests that phentermine and mazindol, compared with placebo, result in modest weight loss over short periods in people more than 15 percent overweight. Weight regain was found after stopping treatment and after longer treatment periods. We found no major evidence of serious adverse events associated with phentermine or mazindol. We found insufficient evidence about diethyl-propion, fluoxetine, or sibutramine plus orlistat for weight loss. Dexfenfluramine, fenfluramine, and the combination of fenfluramine plus phentermine have been associated with valvular heart disease and pulmonary hypertension. Phenylpropanolamine has been associated with increased risk of hemorrhagic stroke.


Three systematic reviews and one subsequent RCT have found that orlistat plus a low-calorie diet modestly increases weight loss in adults with obesity compared with placebo plus diet. We found no evidence about effects on weight following discontinuation or on long-term adverse effects.

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