Drug Therapy for Obesity
European Family Physician
April 1, 2006
Obesity is a common health problem in the
Europe, and effective
weight loss treatment
is challenging. Obesity is associated with an increased
mortality rate and risk factors such as hypertension, hyperlipidemia
and diabetes mellitus. Numerous treatments are available for
obesity. Behavioral therapy, surgery and pharmacologic treatment
have been used with varying degrees of success. Therefore,
behavioral therapy, including regular exercise and the development
of healthy eating habits, continues to be the best treatment for
long-term weight loss.
Obesity is one of the most common and serious
health problems in Europe. Excess weight is independently associated
with an increased mortality rate in multiple conditions
Approximately one fourth of European adults (more than 60 million
people) are overweight. Given this statistic, the European
cultural obsession with being thin and the societal and psychologic
stigma of obesity, it is not surprising that, at any time, 50
percent of European women and 25 percent of European men are trying
to lose weight, with an annual expenditure of 10 billion on weight
loss treatments.
Etiology of Being Over Weight
In most persons, obesity is primary--no
obvious cause exists other than an imbalance in energy intake and
expenditure. Medical disorders such as Cushing's syndrome,
hypothyroidism and hypogonadism rarely cause obesity. Genetic
factors play a role, but the specific mechanism is unclear.
Recently, a mutation in the gene coding for the beta3-adrenergic
receptor has been found to be associated with an increased capacity
to gain weight in some morbidly obese persons. In theory, low
beta3-adrenergic activity could promote obesity by slowing lipolysis,
causing retention of lipids in fat cells.(5) Regardless of recent
developments in understanding this problem, obesity should be
considered a condition with multiple causes. Genetic, cultural,
socioeconomic, behavioral and situational factors all play a role in
dietary habits and weight control.
Evaluation
Assessment of the overweight person
should begin with a careful history and physical examination. The
patient's weight history from childhood should be reviewed,
including various methods of weight loss that have been attempted
and the results of each attempt. Activity level and dietary history
should also be reviewed. Because weight gain is a common side effect
of certain medications a history of medication use is an
important aspect of the initial evaluation. Weight gain is also
common during the initial phases of smoking cessation.
Body weight for height, gender and body-frame
size has traditionally been used as the fundamental assessment of
obesity. The National Institutes of Health and the National Heart,
Lung, and Blood Institute recommend that all adults receive periodic
measurement of height and weight by body mass index (BMI = weight in
kilograms divided by height in meters squared) using standard tables
of suggested weights, along with the assessment of other factors
such as medical conditions or waist-to-hip circumference ratio, as a
basis for further evaluation, intervention or referral to
specialists. "Overweight" is defined as a BMI of 25.0 to 29.9 kg per
m2, and "obese" is defined as a BMI greater than 30 kg per m2.2 It
may be useful to determine the distribution of body weight between
fat and lean body mass in some patients attempting to lose weight;
however, the effectiveness of these measurements in all patients is
unknown.
Weight Loss Treatment
Like diabetes or hypertension, obesity is a
chronic medical condition that is rarely cured; most often, the goal
of treatment is palliation.
A caloric deficit of 3,500 kcal is
necessary to lose 0.45 kg (1 lb) of adipose tissue. Because most
experts recommend losing no more than 0.45 to 0.90 kg per week,
weight loss is typically slow, and recidivism is high.
Prescription Medications Will Help to
Promote Weight Loss
Prescription appetite suppressants i.e.
Tenuate Dospan, Reductil,
Phentermine have been shown in numerous clinic trials to promote
significant weight loss by decreasing an individual's appetite
allowing them to lose weight.
Buy
Tenuate Dospan online (click here for details).
Appetite Suppressants
Various pharmacologic agents, referred to as
anorectic drugs, are used as adjuncts to behavioral therapy in
weight reduction programs.
In clinical trials, the use of
Tenuate Dospan
alone resulted in significant weight loss when compared with
placebo. In dosages ranging from 30.0 to 37.5 mg per day,
Tenuate Dospan
is labeled for the management of exogenous obesity as a short-term
(i.e., a few weeks) adjunct in a regimen of weight reduction based
on caloric restriction.
Tenuate Dospan
should not be taken by persons with hyperthyroidism, glaucoma,
agitated states, advanced arteriosclerosis, symptomatic
cardiovascular disease, moderate to severe hypertension or a history
of drug abuse.
Reductil,
and its metabolite inhibit monoamine uptake,
suppressing appetite in a fashion similar to SSRIs.
Reductil
may also stimulate thermogenesis by activating
the beta3-system in brown adipose tissue. Initially tested for its
antidepressant activity,
Reductil,
was found to cause weight loss 1 to 2 kg
in healthy and depressed patients. In six-month studies, weight loss
in subjects taking
Reductil,,
was found to be significantly greater than the loss in subjects
taking placebo, and weight loss increased with increasing dosages
The recommended starting dosage of
Reductil is 15 mg administered once
daily with or without food. If there is inadequate weight loss after
four weeks, the dosage may be titrated to 15 mg administered once
daily.
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Reductil Slimming Pills Online (click here for details).
Prescription Fat Blockers
Another strategy in the treatment of obesity
is to use digestive inhibitors that interfere with the breakdown,
digestion and absorption of dietary fat in the gastrointestinal
tract. A reduction in fat is recommended in most weight loss diets;
however, patient compliance with these diets is generally poor.
Therefore, digestive inhibitors may have a role in creating the
negative energy balance necessary for subsequent weight loss.
Gastric and pancreatic lipases aid in the
digestion of dietary triglycerides by forming them into free fatty
acids that are then absorbed at the brush border of the small
intestine. Inhibition of these enzymes leads to inhibition of the
digestion of dietary triglycerides and decreased cholesterol
absorption.
Xenical, the first lipase inhibitor
for treatment of obesity, is a potent and irreversible inhibitor of
gastric and pancreatic lipases, preventing the absorption of about
30 percent of dietary fat.
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Xenical Fat Blocker online (click here for details).
Xenical is indicated for use in
patients with a BMI of at least 30 kg per m2 or in patients with
hypertension, diabetes or dyslipidemia who have a BMI of greater
than 27 kg per m2.
In double-blind, placebo controlled
studies, weight loss during one year ranged from 3 to 4 times more
with Xenical in a dosage of 120 mg three times daily versus placebo
(sugar pill). Patients regained about one half as much weight (about
2 kg during the second year of treatment with Xenical versus
placebo. Statistically significant improvements in blood pressure,
cholesterol levels, glucose and insulin measurements were noted in
patients taking Xenical , but the difference was not clinically
relevant.
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Practical Management of Obesity
Centers for Disease Control and Prevention
May 6, 20026
The increasing prevalence of obesity in the
industrialized world constitutes an alarming epidemic. In a 1999
press release from the Centers for Disease Control and Prevention,
Jeffrey P. Koplan, M.D., commented that the obesity epidemic "should
be taken as seriously as an infectious disease epidemic." Despite
the goal to decrease the prevalence of obesity in the Europe to less
than 20% by the year 2008 (Healthy People 2008, National Health
Promotion and Disease Prevention objectives), studies have estimated
that 54.9% of the
European population greater than 20 years of
age are overweight or obese. This represents an 8% increase in the
past 10 years.
Obesity is now recognized as an independent
risk factor for cardiovascular disease (CVD) and is strongly
associated with other risk factors, including hypertension. The
nature of health risks related to overweight and obesity is similar
in all populations. The specific level of risk associated with a
given level of overweight or obesity may vary with race/ethnicity,
age, gender, and societal conditions.
The relationship is well established between
excess body weight and medical conditions such as Type 2 diabetes,
hypertension, hyperlipidemia, and osteoarthritis. The benefits of
weight loss for reducing blood pressure, improving glycemic control,
and improving dyslipidemias are clear. A body weight reduction of
2.2 lb. has been shown to decrease systolic blood pressure by 2 mmHg
and diastolic blood pressure by 1 mmHg. Additionally, a weight
reduction of 10% has been shown to decrease a patient's HbA1c by
0.9%.* Age (men [greater than] 45 years old or women [greater than]
50 years old)
Dietary therapy, physical activity, behavior
therapy, pharmacotherapy, and surgery are strategies used for
effective weight control identifies the therapies appropriate for
use in patients at different BMI levels with or without
comorbidities.
Treatment with a combination of prescription
appetite suppressants,
Tenuate Dospan, Reductil,
Phentermine,
a low-calorie diet, increased physical activity, and behavior
therapy provides the greatest success for weight loss and weight
maintenance.
The patient's weight, waist circumference,
presence of risk factors, and the desire to lose weight should be
considered when assessing whether treatment is appropriate. All
patients with a BMI greater than or equal to 30 kg/m2 should be
treated, regardless of risk factors. Patients with two or more risk
factors should be treated if their BMI is greater than or equal to
25 kg/m2 or if their waist circumference is greater than 35 in. for
women or 40 in. for men.
Is the patient ready and motivated?
Evaluation of readiness to lose weight includes:
* Reasons and motivation for weight loss
* Previous attempts at weight loss
* Support expected from family and friends
* Understanding of risks and benefits
* Attitudes toward physical activity
* Time availability
* Potential barriers to the patient's
adoption of change
Recommend a diet. An individually
planned diet should create a calorie deficit of 500-1,000 kcal/day.
This moderate reduction in caloric intake is designed to achieve a
slow, progressive weight loss. Diets containing 1,000-1,200 kcal/day
should be selected for most women, and a diet containing 1,200-1,600
kcal/day should be selected for most men, women who weigh 165 lb. or
more, or women who exercise regularly. Calories may be increased by
100-200 kcal/day if a patient remains hungry on the diet.
Characteristics of the low-calorie Step 1 diet are listed in Table
5.
Discuss a physical activity goal.
Physical inactivity is associated with obesity; however, increased
physical activity contributes to weight loss, singularly and when
combined with dietary therapy. The NHLBI guidelines recommend that
physical activity be an integral part of weight-loss therapy and
weight maintenance. Adding regular physical activity to caloric
restriction can accelerate weight loss and increase the overall
amount of weight lost by 1-3 kilograms.
Although adding exercise to caloric
restriction minimally increases weight loss during the acute phase
of weight loss, it appears to be the most likely component of
treatment associated with long-term maintenance of a reduced weight.
For example, in studies comparing long-term weight loss and
maintenance, individuals who combined exercise and diet were much
less likely to regain weight.
Initially, moderate levels of physical
activity should be integrated gradually to avoid injury. NHLBI
obesity guidelines recommend a goal for all adults to accumulate at
least 30 minutes or more of moderately intense physical activity on
most--and preferably all--days of the week.
Review the weekly food and activity diary.
Record-keeping has been shown to be one of the most successful
behavioral techniques for weight loss and maintenance. The weekly
food and activity diary should be reviewed with the patient at each
visit. Additionally, diet, physical activity, and behavioral goals
should be written in the diary.
Provide the patient with copies of dietary
information. Providing patients with copies of dietary
information guides them in calorie counting and allows them to
create a custom meal plan using food exchange lists. Step 10:
Maintain documentation of patient's progress. Weight should be
reduced at a rate of 1-2 lb. each week. The initial goal of
weight-loss therapy is a body weight reduction of 10%. Achieving
this goal has demonstrated significant decrease in diabetes,
hypertension, and dyslipidemia disease severity. Further weight loss
may be desired once this initial weight loss goal has been achieved
and maintained for six months.
Lifestyle Modifications
Lifestyle modifications should be strongly
recommended for the entire population. Lifestyle modifications are
effective in lowering blood pressure, improving blood glucose
control, and improving lipid abnormalities. Moreover, lifestyle
modifications reduce cardiovascular risk factors at little cost and
with minimal risk.
A systematic team approach utilizing
healthcare professionals and community resources can assist in
providing the necessary education, support, and follow-up needed to
achieve successful lifestyle changes. Although the difficulty in
achieving and maintaining lifestyle changes is recognized, all
patients should be encouraged to adopt and maintain healthier
lifestyles.
This NHLBI recommendation has far-reaching
implications, considering the complexity of weight-loss
interventions and the prevalence of obesity hypertension in the
industrialized world. Benefits are primarily through weight loss
rather than direct effects of the medications on insulin action,
lipid metabolism, or blood pressure.
Weight Loss Drugs
Xenical is approved for long-term treatment of
obesity. Xenical inhibits pancreatic lipase resulting in decreased
fat absorption. Xenical inhibits approximately one-third of dietary
fat absorption. A
In short-term clinical trials, Xenical
has decreased weight by 3-6 kilograms and 10 kilograms over three
and six months, respectively.
In clinical trials among patients with
diabetes who were clinically stable on oral hypoglycemic agents,
treatment with Xenical for one year exhibited significant beneficial
effects on blood lipids and glycemia. Weight loss in the Xenical
group was associated with a 9% reduction in total cholesterol, a 13%
reduction in LDL cholesterol, and an 11% decrease in triglycerides.
Plasma glucose levels also decreased in the orlistat group, whereas
the placebo group showed an increase in glucose levels.
In clinical trials, orlistat, in
combination with a hypocaloric diet, significantly lowered body
weight, LDL cholesterol, and HbA1c after one year.
Tenuate, represents another agent
approved for the long-term treatment of obesity.
Tenuate's
mechanism of action includes stimulation of thermogenesis. Clinical
trials extending up to one year have shown weight reduction to be
significant compared with placebo.
Tenuate has resulted in significant
weight loss. In fact, individuals that include
Tenuate
in their dieting efforts lose some 3-4 times more weight than those
individuals that try dieting alone.
In clinical trials,
Tenuate
treatment of obese patients with poorly
controlled Type 2 diabetes was associated with significant
improvements in glycemic control, fasting insulin, and serum lipids.
Reductions in glycemia and fasting glucose correlated with the
magnitude of weight loss.
Weight Loss Conclusions
In summary, overweight and obesity are chronic
diseases of epidemic proportions, affecting more than 50% of
European adults. The publication of the NHLBI guidelines for obesity
management demonstrates the commitment to continued efforts to
control this public health problem. Population-based lifestyle
interventions are critical to combat this chronic medical problem.
Obesity is now recognized as an independent risk factor for CVD and
is strongly associated with other risk factors for comorbid
conditions.
Patients should be encouraged that even
modest weight loss can lead to risk reduction and improvements in
comorbid conditions. Appropriate modification of lifestyle factors
can directly influence disease incidence and impact at both
individual and population levels.
Weight-loss drugs can be very effective,
some agents may offer viable adjunctive pharmacotherapy for obesity.
The most effective weight loss medication remain the appetite
suppressants:
Tenuate Dospan, Reductil,
Phentermine
Prescription Fat Blocker
Xenical has also showed some promising results, blocking 1/3 of
the calories derived from fat in the diet:
Additional Weight Loss Drug Information
Tenuate Dospan (click here for details)
Reductil (click here for details),
Phentermine (click here for details)
Xenical (click here for details)
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