Treatment of Obesity 129may represent relatively favorable outcomes. In addition,
mean weight changes provide only a partial view of long-
term outcome. A fuller perspective may be gleaned from an
examination of categories of partial success. For example,
Kramer, Jeffery, Forster, and Snell (1989) reported an overall
mean weight loss of 2.7 kg at 4.5-year follow-up. However,
an analysis by categories of relative success revealed that ap-
proximately 20% of the subjects maintained losses of 5 kg or
more, suggesting a notable degree of success for a signi“cant
number of individuals.
Pharmacotherapy
Four types of medications have been used to treat obesity.
These include (a) noradrenergic agents, (b) serotoninergic
agents, (c) combined noradrenergic and serotoninergic agents,
and (d) lipase inhibitors. Recent years have witnessed major
changes in the medications available for weight loss. The
serotoninergic drugs, fen”uramine (Pondimin) and dexfen”u-
ramine (Redux), were withdrawn in 1997 due to their associa-
tion with occurrence of heart valve disease (Connolly et al.,
1997), and in 2000, the over-the-counter weight-loss products,
Accutrim and Dexatrim, which contain the noradrenergic
ingredient phenylpropanolamine, were withdrawn due to con-
cerns about increased risk of stroke (FDA, Nov. 6, 2000).
Since 1997, the Food and Drug Administration has approved
two new anti-obesity agents, sibutramine (Meridia; Knoll
Pharmaceutical Company) and orlistat (Xenical; Roche Phar-
maceutical Company). Table 6.4 summarizes the current sta-
tus of drugs used to treat obesity. In the following section, we
describe sibutramine and orlistat, the two newest ant-obesity
agents.
Sibutramine is a combined serotonin and noradrenaline
reuptake inhibitor. Rather than decreasing appetite, sibu-
tramine works by increasing satiety after the onset of eating.
Sibutramine may also produce a small increase in basal meta-
bolic rate (Hansen, Toubro, Stock, Macdonald, & Astrup,
1998). In controlled trials lasting 6 to 12 months, sibutramine
(15 mg per day) produced mean body weight reductions of
6% to 7%, compared to 1% to 2% for placebo (Bray et al.,
1999; Jones, Smith, Kelly, & Gray, 1995). Weight loss occurs
in the “rst six months of use and tends to plateau thereafter.
Sibutramine may also enhance the effects of intensive di-
eting. For example, Apfelbaum et al. (1999) showed that sub-
jects who initially lost 6 or more kg through four weeks of
very low calorie dieting increased their weight losses by an
additional 5.2 kg through the use of sibutramine, whereas
subjects on placebo gained 0.5 kg.
The major drawback of sibutramine lies in its effect on
blood pressure. Sibutramine produces a modest mean
increase in blood pressure (about 2-mm Hg systolic and dias-
tolic at the 15-mg dose). However, some people (approxi-
mately 17%) who take sibutramine experience an increase of
10-mm Hg or more in diastolic systolic blood pressure (com-
pared to 7% of subjects taking placebo). A 2-mm rise in
diastolic blood pressure increases the risk of coronary heart
disease by 6% and increases the risk of stroke by 15% (Cook,
Cohen, Hebert, Taylor, & Hennekens, 1995). Therefore, pa-
tients with a history of heart disease, stroke, hypertension, or
other risk factors for heart disease should not take sibu-
tramine, and those on sibutramine must have their blood
pressure monitored frequently (Hensrud, 2000; Knoll Phar-
maceutical Co., 2000). Other less serious side effects of sibu-
tramine include headache, dry mouth, anorexia, constipation,
and insomnia.
Orlistat is a gastric and pancreatic lipase inhibitor (Roche
Laboratories, 2000). Rather than suppressing appetite or in-
creasing satiety, orlistat works by preventing the digestion
and absorption of up to 30% of fat intake. In a large-scale,
randomized controlled trial (Davidson et al., 1999), treatment
with diet plus orlistat (120 mg, 3 times a day) for two years
produced a 7.6% weight loss while treatment with diet
plus placebo resulted in a 4.2% reduction. Maximum weight
loss with orlistat typically occurs after 8 to 12 months of
treatment, and 25% to 30% of the weight lost during the “rst
year is regained during the following year, despite continued
treatment (Davidson et al., 1999; L. Sjöstrom et al., 1998).
Nonetheless, weight loss after two years of treatment with
diet plus orlistat remains signi“cantly greater than treatmentTABLE 6.4 Current Status of Drugs Used to Treat Obesity
Type of Agent Generic Name Trade Name Current StatusNoradrenergic Benzphetamine Didrex Available
Diethylproprion Tenuate, Available
Tepanil
Mazindol Mazanor, Available
Sanorex
Phendimetrazine Anorex, Available
Obalan,
Wehless
Phentermine Adipex-P, Available
Fastin,
Ionamin
Phenylpropanolamine Accutrim, Withdrawn
Dexatrim
Serotoninergic Dexfen”uramine Redux Withdrawn
Fen”uramine Pondimin Withdrawn
Fluoxetine Prozac, Not approved
Lovan
Combined Sibutramine Meridia Available
noradrenergic
serotoninergic
Lipase inhibitor Orlistat Xenical Available