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dexfenfluramine, and phenylpropanolamine have been withdrawn because of se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.