Download Weight-loss Medications: Controversies and Benefits

Weight-loss Medications:
Controversies and Benefits
Karen Lilyquist, RN, RD, PhD, LD
Sarah Coffin, RD, MS
Goal and Objectives
The goal of this weight-loss medication program is to educate dietitians, dietary managers,
fitness professionals, health educators, physical therapists and physicians about the risks,
benefits and appropriateness of FDA-approved weight-loss medications. After studying the
information presented here, you will be able to:
• Discuss the pros and cons of the use of prescription drugs in the treatment of
obesity
• Identify appropriate candidates for weight-loss drugs as part of a comprehensive
program
• List FDA-approved weight-loss drugs and explain the pharmacological effects of
the weight-loss drugs in the body
See “How to Earn Continuing Education Credit” at the end of this course.
“I’ve tried everything to lose weight on my own. What about weight-loss drugs?”
If your job involves weight-management counseling, this question probably sounds familiar.
Whether you support or oppose the use of prescription drugs as a treatment for obesity, it is
clear: the issue is here to stay. Typically, medications for weight loss are prescribed after
conventional diet, exercise and lifestyle methods tried for at least six months fail.1,2 Because
of the growing epidemic of obesity, diet failures, and new pharmacological developments for
weight-loss products showcased in professional journals, television reports, consumeroriented magazines and national newspapers, weight-loss medications have remained at
center stage. At least 30 prescription weight-loss medications are in research and
development. Will one be the “magic bullet” for permanent, safe weight reduction?
There aren’t any reputable statistics regarding the use of prescription weight-loss
medication.3 In an older study, prevalence of prescription diet drug use in U.S. adults from
1996 to 1998 was estimated at 2.5% (4.5 million). In 2001, other researchers used data from
insurers and estimated use of prescription diet drugs at 2.4%. What is known is that far fewer
people are using these medications than are approved for them, and use is significantly higher
among women than men.4 Approximately 25% of the users have a BMI <27, suggesting that
25% are using the medications inappropriately.5
In an era of direct marketing of prescription medications where consumers are urged to “Ask
Your Doctor about … [Drug],” consumer demand can be stimulated quickly. The lessons
learned from the commercial success of the infamous phen-fen (phentermine-fenfluramine)
will not be forgotten. In 1992, 60,000 fenfluramine prescriptions were written. In 1997, in
part as a result of an aggressive marketing campaign, 10 million were written for the
combination phen-fen.6 That September, drug companies withdrew fenfluramine from the
U.S. market due to the incidence of heart valve defects in those taking the medication.
As we search for the solution to chronic overweight and obesity problems, it is crucial that
healthcare providers of various disciplines understand these clients are under tremendous
pressure to seek drug therapy. Friends and family members often hold strong opinions, from
very positive comments to suggestions that they cannot control their eating habits through
some sort of weakness or laziness. Obesity and overweight are multi-faceted problems,
involving diet and lifestyle choices, but also complex biochemical processes and
overwhelming environmental influence (e.g., availability and advertisement of high-calorie
foods). Helping people obtain unbiased and credible information about weight-loss
medications is an important role for healthcare providers.
Pros and Cons
The use of prescription drugs in the treatment of obesity is controversial. Those who support
their use argue that obesity is an incurable disease. Some compare it to hypertension — also
incurable, but often well controlled with anti-hypertensive medication. Proponents of drug
treatment for the obese argue that obesity can be similarly controlled, but not cured, with
medication.
Proponents also suggest that the small amount of weight loss attributable to the medication
improves insulin sensitivity, blood glucose levels, blood lipid levels and blood pressure. They
suggest that medications can help “kick start” weight-loss efforts that also include lifelong
changes in diet and physical activity patterns.7
Those who oppose the use of medications argue that they are of no real value in maintaining
long-term weight loss and that the risks outweigh the benefits. Many question if the relatively
small amount of weight loss resulting from prescription medications is clinically significant.
Others see it as another “quick fix.” Most suggest that in theory, medication can be used as
part of a comprehensive treatment program, but in practice, medication is a monotherapy.
Organizational recommendations have also been mixed. Clinical Guidelines on the
Identification, Evaluation, and Treatment of Overweight and Obesity in Adults concluded that
weight-loss medications can complement a comprehensive treatment program that includes a
low-calorie diet, physical activity and behavior therapy in carefully selected patients (an
update of this report is expected soon).8
In its 2009 position paper on weight management, the Academy of Nutrition and Dietetics
concluded:9
FDA-approved weight-loss medications may be part of a comprehensive weight
management program. RDs should collaborate with other members of the healthcare
team regarding the use of FDA-approved weight-loss medications for people who meet
the NHLBI (National Heart, Lung and Blood Institute) criteria. Research indicates that
pharmacotherapy may enhance weight loss in some overweight and obese adults.
The National Association to Advance Fat Acceptance (NAAFA) strongly discourages people
of any size from taking drugs for weight loss. It bases its position on the fact that there are
negative health effects associated with the drugs, and that the consumer has not been
protected from dangerous weight-loss drugs in the past. NAAFA also condemns obesity
research and drug manufacturers who profit from inadequately tested weight-loss drugs.10
It is important that practitioners consider the use of pharmacological intervention for
unsuccessful clients because of overwhelming evidence that obesity contributes to health
problems, and that obesity continues to surge unabated in this country. The challenge for all
healthcare practitioners is to help people achieve their weight-loss goals safely, and weightloss medication may be part of that plan.
Selection and Continuance Criteria
Candidates for weight-loss drugs should meet the following:8
• BMI at or above 30 kg/m2
• BMI 27 kg/m2 to 29.9 kg/m2 with comorbidities (e.g., type 2 diabetes,
hypertension, heart disease, obstructive sleep apnea or metabolic syndrome)
Those with a BMI < 25 kg/m2 should not be prescribed weight-loss medications since the risk
of the medication outweighs any medically significant benefit. In addition, these medications
should not be used in combination with other anorectic agents, including prescribed drugs,
OTC preparations and herbal products.
Short-term clinical trials show obese subjects instructed in dietary management and treated
with anorectic drugs lose more weight on average than those treated with placebo and diet.
Studies of weight-loss medication also show high dropout rates, averaging 30% to 40%, and
that a major barrier is that people do not take the medication as prescribed.11 Those who
begin drug treatment as part of a comprehensive program should be evaluated to determine if
the treatment is being successful.
Success is measured as follows:8
• Drug therapy results in the loss of more than 2 kg of weight in the first month
•
•
Drug therapy results in a 5% weight loss by six months
Improvement of comorbid conditions
Available Weight-loss Medications
Most approved drugs are known as anorexiants (medications that suppress appetite). There is
one approved drug that blocks intestinal fat absorption. Most appetite suppressant drugs are
approved for short-term use of 12 to 16 weeks.
FDA-Approved Weight-Loss Drugs11,12
Generic Name
Trade Names
Description
Orlistat
Xenical (prescription), Alli (OTC) Blocks intestinal fat absorption
Approved for long-term use
Phentermine
Adipex-P, Fastin, Phentride,
Stimulates the release of
Obenix, Oby-Cap, Oby-Trim,
norepinephrine; mild anorexiant
Suprenza, Ionamin
Short-term appetite suppressant
Diethylpropion Anorex, Nobesine, Prefamone,
Short-term appetite suppressant,
Regenon, Tenuate, Tenuate Dospan stimulant
Benzphetamine Didrex
Short-term appetite suppressant,
stimulant
Phendimetrazine Bontril PDM, Plegine,
Short-term appetite suppressant,
X-Trozine, Prelu-2, Melfiat,
stimulant
Adipost, Obezine, Statobex,
Anorex-SR
Lorcaserin
Belviq
Short-term appetite suppressant,
stimulant
Phentermine and Qsymia
Short-term appetite suppressant,
topiramate
stimulant
Sibutramine*
Long-term appetite suppressant
(only available in Europe)
*Only available outside the U.S. as Reductil. The U.S. trade name was Meridia; it was
withdrawn from the U.S. market at FDA request in October 2010.
Orlistat
Orlistat (Xenical, Alli) is the only drug approved by the FDA for long-term use; it is available
by prescription and OTC. Xenical, which contains 120 mg of orlistat, is available via
prescription only. Alli, which contains 60 mg of orlistat, is available OTC.13 (The information
discussed below refers to prescription-strength orlistat only.)
Xenical has a unique mode of action — the inhibition of pancreatic lipase, which results in
reduced absorption of dietary fat. Approximately 30% of the dietary fat consumed is blocked
when the diet contains about 30% of total calories from fat. Consuming Xenical with a low-
fat diet has little effect on fat absorption or blockage. If a patient consumes 2000 kcal/day,
with 30% of calories from fat, the recommended dose of Xenical would likely result in a 200
to 300 kcal/day deficit.14 Xenical should be avoided in those with chronic malabsorption and
cholestasis.15
Xenical is most effective and produces the fewest adverse effects when the meal contains a
fairly even distribution of carbohydrate, protein and fat. Medication intake should be adjusted
to dietary intake. Xenical is effective when taken during a meal or up to one hour after a meal
so adjusting medication is not difficult. If a meal is missed or is very low in fat, Xenical can
be omitted. A high-fat meal (greater than 30% of calorie from fat) should be avoided. Taking
a dose of Xenical with a high-fat meal will likely result in greater GI adverse effects.14
Xenical itself is not absorbed; therefore, adverse effects are associated with the malabsorption
of fat. Unabsorbed fat remains in the GI tract, and adverse effects include fatty stools,
increased number of bowel movements, oily spotting, soft or liquid stools, and fecal urgency.
These symptoms tend to subside over time. The decrease in symptoms may be a result of
learning how to alter the amount of fat consumed. It should not be underestimated how
uncomfortable these adverse effects can be, especially in social and work situations.
Clinicians should encourage open discussion of the negative consequences of using the drug.
A recent study questioned 566 clients who were prescribed Xenical six months earlier.16
Many had stopped taking the drug; a minority were taking the drug inconsistently. The
findings demonstrate that those who lost the most weight showed a decreased belief that there
was a medical solution to weight loss, a decrease in unhealthy eating habits, an increased
belief in taking control of their treatment and an increased belief that the adverse effects of
the drug were a result of both the dietary choices (too much fat) and the drug itself. The fact
that some taking the drug came to the conclusion that they had to decrease fat to prevent the
oily stools forced them to focus on the behavioral aspects of their weight problem and what
they needed to do to lose weight.16
Xenical blocks fat absorption, which includes the absorption of the fat-soluble vitamins, so
supplemental fat-soluble vitamins are needed to ensure adequate amounts are absorbed. The
vitamin supplement is usually taken before bedtime, separate from Xenical, to ensure
maximum absorption. At a minimum, supplemental fat-soluble vitamins should precede or
follow a dose of Xenical by two hours.
A 2007 meta-analysis of overweight and obese people reported that subjects who took orlistat
lost an average of 2.9 kg (6 lb), or 2.9% more than those who received a placebo.11
Approximately 21% of the subjects in all the studies reviewed lost at least 5% of their body
weight; 12% of the subjects lost 10% or more.
Studies show that diabetics who took orlistat, when compared to a placebo, reduced waist
circumference, BMI, blood pressure, fasting glucose and hemoglobin A1c, and improved
some blood lipids (cholesterol, LDL).11 However, orlistat slightly lowered HDL
concentration. As expected, the most frequent adverse effects were GI problems. No studies
reported fat soluble vitamin deficiencies.11
Not all research suggests orlistat therapy is better than alternate weight reduction or weight
management therapies. A recent study compared two potential weight-loss therapies: a lowcarbohydrate, ketogenic diet (LCKD), and orlistat therapy combined with a low-fat diet
(O+LFD). Main outcomes measures were body weight, blood pressure, fasting serum lipid
and glycemic parameters. LCKD led to similar improvements as O+LFD for body weight,
serum lipid levels, and glycemic parameters and was more effective in lowering blood
pressure.12
In 2009 and 2010, the FDA reviewed the safety of orlistat because of reports of serious liver
damage in people taking it. After the review, the FDA issued new warnings about the
possibility of liver injury to both the prescription-strength and OTC orlistat. In 2010, the
FDA required the manufacturer to add a warning about the potential for liver injury to the
labels of Xenical and Alli.17 It is advised that people taking orlistat should be aware of signs
and symptoms that could indicate liver damage.
Phentermine
Phentermine is a stimulant that is similar to an amphetamine, and works by stimulating the
release of norepinephrine to produce an anorectic effect. It has been approved for short-term
use since the 1960s, with as many as 50 million prescriptions written worldwide. It is
designed to be used together with diet and exercise to treat obesity in people with risk factors
such as high blood pressure, high cholesterol and diabetes. Despite its widespread use, the
number of published studies regarding phentermine is small. One long-term study (36
weeks), three short-term studies and a 40-year history of use would suggest it is relatively
safe. Adverse effects have been described as minor, usually agitation or insomnia.6
A recent study documented the prescribing habits of physicians specializing in the treatment
of obesity. Thirty percent of those surveyed responded. Of these (n = 266), almost all
prescribed medications; all recommended phentermine.18 Phentermine is marketed under
several names including Adipex-P, Obenix, Oby-Cap, Oby-Trim, Phentride, Fastin, Suprenza
and Ionamin.
Is phentermine effective? In the long-term study, 108 obese women were assigned to one of
three groups: continuous treatment (36 weeks), intermittent treatment (alternating four weeks
of phentermine treatment and four weeks of no drug treatment), or placebo. All received
behavioral modification, were weighed weekly and were instructed on a 1000 kcal/day diet.
Those who received phentermine for 36 weeks lost an average of 12.2 kg (about 27 lb). The
intermittent treatment group lost 13 kg (about 29 lb), and those receiving a placebo lost 4.8
kg (about 11 lb). Short-term studies reported similar results.6
Phentermine should not be tainted by association with the fenfluramines (the “fen” of phen-
fen). The mechanism of action of phentermine is not the same as the fenfluramines, which are
highly reactive to the serotonin receptor sites in heart valves.
In the late 1990s, phen-fen (phentermine+fenfluramine) became very popular; many
consumers demanded prescriptions from their physicians. The use of fenfluramines spread
like wildfire; they were featured on the cover of Time magazine. In 1997, reports of heart
valve changes in patients using fenfluramines began to emerge. In some cases, the valve
abnormalities were asymptomatic and could only be detected with echocardiograms. In
September 1997, fenfluramine and dexfenfluramine were voluntarily withdrawn from the
U.S. market because of the incidence of valvular regurgitation (the backward flow of blood
due to incomplete valve closure). Initial reports suggested that as many as one-third of those
taking the drugs exhibited changes, although a data review has shown that the incidence was
not that high; valvular regurgitation was an adverse effect in 2% to 12% of fenfluramine
users.19
Duration was an important factor. Those who used fenfluramines for less than four months
(considered short-term) had a lower prevalence of heart valve changes than those who used
them for more than four months. Both medications remain off the market. The American
College of Cardiology recommends that those who have used fenfluramine or
dexfenfluramine (with or without phentermine) get a physical exam to determine if
echocardiography is necessary.19
Given the risk of valvular abnormalities, why did the FDA approve fenfluramines? The
adverse effect was totally unexpected, and there was nothing in the medical literature that
suggested it would occur. In fact, the heart valve defects were discovered by sonographers in
Fargo, North Dakota, who thought that there might be a connection between their obese
patients’ valve defects and the use of phen-fen.20
The lessons learned from phen-fen, coupled with the history of addictive diet drugs, have
many practitioners feeling uneasy about the safety of weight-loss drugs; however, no other
weight-loss medications have the same mechanism as the fenfluramines. All the drugs
currently approved by the FDA for weight loss have minor adverse effects; serious adverse
effects are rare.
Diethylpropion
Diethylpropion is an appetite suppressant similar to an amphetamine and is sold under the
trade names Anorex, Nobesine, Prefamone, Regenon, Tepanil, Tenuate and Tenuate Dospan.
It is indicated for exogenous obesity for patients with a BMI >30 kg/m2 as a part of a shortterm plan in obese patients who have not been successful with diet and exercise. It is also
recommended to be used with a lifestyle, exercise and diet-modification program.
Diethylpropion stimulates the central nervous system, and may increase heart rate and blood
pressure. Although approved for adults and teenagers, it is not approved for use in children
younger than 16 years. Those with diabetes must be monitored carefully, as it may affect
blood sugar levels. Adverse effects may include dry mouth, upset stomach, anxiety and
increased urination. Diethylpropion comes in various dosages depending on the trade name
prescribed.21
Benzphetamine
Benzphetamine hydrochloride is also prescribed under the trade name Didrex. It is an
anorectic and appetite suppressant, and is indicated for short-term use in managing
exogenous obesity. As with other drugs in this class, a regimen of diet, exercise and lifestyle
changes is recommended. Patients need to have a BMI of at least 30 kg/m2 and to have been
unresponsive to traditional weight-loss recommendations. As with other amphetamine-like
substances, Benzphetamine hydrochloride tablets are contraindicated in patients with
advanced arteriosclerosis, symptomatic cardiovascular disease, moderate to severe
hypertension, hyperthyroidism, known hypersensitivity or idiosyncrasy to sympathomimetic
amines, and glaucoma. Benzphetamine should not be given to patients who are in an agitated
state or who have a history of drug abuse. It should be used carefully with diabetics as it can
affect blood sugar levels. Adverse effects may include shortness of breath, chest pain,
confusion and increased blood pressure.22
Phendimetrazine Tartrate
Phendimetrazine tartrate is an anorectic agent with similar activity as other amphetamine type
medications for weight loss. Trade names include Bontril PDM, Obezine, Adipost, Statobex,
Anorex-SR, Plegine, Prelu-2, X-Trozine and Melfiat. It is indicated for short-term use in the
management of exogenous obesity after traditional diet, exercise and lifestyle changes have
failed. Patients using phendimetrazine tartrate should have an initial BMI ≥ 30 kg/m2 or ≥ 27
kg/m2 in the presence of other risk factors including controlled hypertension, diabetes, and
hyperlipidemia.23 Actions of the medication include central nervous system stimulation and
elevation of blood pressure. Adverse effects may include sleep disorders, dry mouth, anxiety
and GI complaints. Tachyphylaxis and tolerance has been found in all drugs in this class that
have been examined for these phenomena.
Lorcaserin
After the phen-fen scare, no weight-loss drugs were approved for many years. Lorcaserin was
approved initially in 2009, but the FDA rejected final approval due to evidence of breast and
brain tumors in rats, marginal weight loss in diabetics and psychosis. 24 After further testing
and trials, lorcaserin (Belviq) was FDA approved in 2012. It was the first new weight-loss
medication approved in 13 years.
Lorcaserin is a serotonin agonist and works by suppressing the appetite center of the brain.
Specifically, it activates brain receptors for serotonin, a neurotransmitter that signals satiety
and satisfaction. It is indicated for patients with BMI >30 kg/m2 or >27 kg/m2 with the
presence of comorbid diseases including type 2 diabetes, hyperlipidemia and hypertension.
Reported adverse events are low, but weight lost while on the medication is not sustained
after the pill is discontinued. Long-term effectiveness is not known as the drug is relatively
new.25
Trial data submitted to the FDA showed that half the dieters without type 2 diabetes lost at
least 5% of starting weight (an average of 12 lb), compared with only 23% of those taking
placebo. Healthy diet and lifestyle are recommended when taking this medication. If people
taking lorcaserin do not lose at least 5% of their body weight after 12 weeks, discontinuation
of the medication is recommended. Possible adverse effects may include mood changes,
agitation, shortness of breath, slow heart rate and GI complaints. Despite FDA approval,
some advisory panel members still feel there is a lingering uncertainty about the connection
between lorcaserin and heart valve disease and tumors. They question whether the potential
benefits of lorcaserin outweigh the potential risks.24
Qsymia
Qsymia, formerly known as Qnexa (phentermine/topiramate), is another weight-loss
medication approved by the FDA in 2012. It is a combination of two compounds: topiramate
(Topamax), which is an anticonvulsant and phentermine, which is an appetite suppressant.
The FDA rejected Qnexa in 2009 due to concern over dangerous arrhythmias and psychiatric
disturbances. More recent trials have shown the combination of the two drugs to be effective
and relatively safe, and one study has shown an improvement in blood pressure and reduction
in sleep apnea.26,27
Qsymia is recommended only for obese patients with a BMI > 30 kg/m2, or 27 kg/m2 who
also have high blood pressure, type 2 diabetes or high cholesterol. Exercise and lifestyle
changes are also recommended when using this drug. Adverse effects include tingling in the
fingers and toes, and constipation. Since the drug may also elevate heart rate, the FDA
doesn’t recommend the drug for patients with glaucoma, hyperthyroidism, recent heart
disease or stroke.
Qsymia comes in four strengths, ranging from 3.75 mg to 15 mg. Trials of Qsymia showed
that after a year of taking the drug, patients lost an average of 7% to 9% of their body weight.
If patients do not lose at least 3% of their body weight, a dose increase is recommended. If
those patients do not lose at least 5% of their body weight in 12 weeks, they should stop the
drug.28
Contrave
Contrave is a weight-loss medication that has not yet gained approval from the FDA due to
concerns about the cardiovascular profile. Contrave is a combination of two drugs, bupropion
(Wellbutrin), which is an appetite suppressant and antidepressant and naltrexone (ReVia),
which works by blocking opioid receptors to decrease cravings.29 Recent reports suggest the
manufacturer of Contrave may submit another drug application for FDA approval in the
second half of 2013.
The FDA requested a randomized, double-blind, placebo-controlled trial of sufficient size
and duration that would show that the risk of major adverse cardiovascular events in
overweight and obese subjects treated with Contrave does not adversely affect its benefit-risk
profile. In February 2012, the company agreed to a Special Protocol Assessment for the
Contrave outcomes trial; in June 2012, the Light Study was initiated. FDA approval is
expected in 2014.30
Sibutramine
Sibutramine (Meridia [U.S. trade name]) was an appetite suppressing weight-loss medication
approved by the FDA for long-term use. Sibutramine was an example of a serotoninnorepinephrine reuptake inhibitor: because cellular uptake is inhibited, serotonin and
norepinephrine continue to circulate in the blood and have an anorectic effect.
In 2010, following an FDA review of the SCOUT (Sibutramine Cardiovascular Outcomes)
study, Abbott Laboratories voluntarily removed sibutramine from the U.S. market, at the
request of the FDA. SCOUT showed an increased risk of heart attack and stroke in patients
who received long-term treatment and who had pre-existing cardiovascular conditions,
compared with those taking a placebo.31
The FDA had safety concerns when it approved sibutramine initially, but at the time, the
FDA believed the benefit of weight loss was greater than the risk of increased blood pressure
and heart rate. Outside of the U.S., this drug is sold under the name of Reductil.
Effectiveness of Medication
Weight loss. The effect of any obesity medication on weight loss is modest (realistically 3%
to 8% of initial body weight). For most users, weight-loss medications alone will not help
them reach the often-recommended 10% reduction in body weight. People report that they
hope to lose 30% of original body weight; this level of reduction is not likely to be achievable
with the use of weight-loss medications alone.7 Britain’s National Institute for Health and
Clinical Excellence recommends that weight-loss medication treatment be discontinued if a
5% loss in weight has not occurred in three months.11
Reduction of disease risk. Unfortunately, there is a limited amount of information about the
effects of weight-loss medications on disease risk. This is a result of the typical study
protocol, which generally excludes obese patients with clinical conditions such as type 2
diabetes, hypertension or dyslipidemias, especially if these conditions are being treated with
medications. It is known that weight loss itself reduces blood pressure, elevated blood
glucose and elevated blood lipids. One 2008 study suggests that a weight loss of 10 kg is
associated with a decrease in blood pressure of 10 mmHg, total cholesterol of 10%, LDL
cholesterol of 15%, triglycerides of 30%, fasting glucose of 50% and an increase in HDL
cholesterol of 8%.15
Effectiveness and the clinical significance of any weight loss has always been a troubling
issue for the FDA. In 1938, the Food, Drug, and Cosmetic Act required drugs to show
evidence of safety but not effectiveness. It was not until 1962 that the act was amended to
require evidence of effectiveness. The critical question today is (although there is no FDA
mandate that it be answered): “Do the benefits outweigh the risks?”32
Although the FDA has struggled with finding a way to judge the effectiveness of weight-loss
medications, the easily quantifiable way is to measure pounds lost in both treatment and
placebo groups. Scientists in the 1970s were unable to define a way to determine if weight
loss was “clinically significant.” In other words, if the treatment group loses an average of 5
lb and the placebo group loses an average of 2 lb (this difference is statistically significant),
then the drug is considered effective.
But does that 3-lb difference in weight loss by those who took the weight-loss medication
have any positive clinical significance on health, such as lowering blood pressure or blood
lipids?32
The inability to answer that clinically significant question bothered scientists in the 1970s,
but it becomes even more critical today because millions more people are obese and weightloss medication use is higher than three decades ago. FDA guidelines for critical evaluation
of weight-loss drugs were written in 1996 and are in need of updating to address clinical
significance and the risk-to-benefit ratio.33 Although more studies are being conducted to
determine the effect of a weight-loss medication on health outcomes, especially those at risk
for or already diagnosed with type 2 diabetes, the number of studies conducted is still small.
NAAFA advocates that the FDA should deny approval of any weight-loss medication that
does not show health benefits. This organization suggests that the FDA pose the same
question for weight-loss medications as it does for other drugs: Does this treatment
improvement health? Approval at the present time is based only on the ability to produce
weight loss.
All healthcare providers prescribing or recommending a weight-loss program that includes
the use of medications should read the package insert and full prescribing information
carefully as many medications are contraindicated when combined with current medications
and preexisting conditions such as diabetes, kidney failure and others. Most weight-loss
medications are only advised for short-term use along with diet, exercise and lifestyle
changes. Addiction is a potential adverse effect when used for longer periods of time. All
require frequent follow-up with a physician, as well as other healthcare providers including
registered dietitians, psychologists, exercise physiologists and others.
Medications: Only One Part of the Treatment Plan
A reasonable expectation for an obese adult using a weight-loss medication is that 3% to 8%
more weight will be lost than without its use. Of course, drugs alone are not the answer, and
exercise and changes in diet are to be complimentary treatments.
Lifestyle modification (including regular exercise and reduced-calorie diet) has been shown
to increase weight loss more effectively than drug use alone. Studies suggest that this may
also be true in adolescents and children, but there are far fewer studies upon which to draw
conclusions. Xenical is the only prescription weight-loss drug approved for use in adolescents
older than 12 years; Alli is not approved for adolescents under the age of 18. Use of weightloss medications with children and adolescents must be done on a case-by-case basis.33
Whether the potential risks of weight-loss medication for such a small amount of weight loss
(3% to 8% more weight than without the use of drugs) outweigh the benefits is not known;
however, it is known that maintenance of any weight loss requires a commitment to routine
exercise, diet and lifestyle changes. Many people cannot or do not maintain, so they regain
the lost weight. One recommendation is that weight-loss medications be prescribed or
continue to be prescribed only to those who are committed to daily activity/exercise and
healthy eating. This strategy allows the medication to become part of the treatment plan and
not a “quick fix.”
Future Possibilities
In 2011, Americans spent approximately $61 billion on weight-loss products, including
weight-loss programs, special foods, diet soda, appetite suppressants, gym memberships, diet
books, exercise DVDs and surgery.34 Sales of obesity drugs in the U.S. more than tripled in
2007, reaching $421 million. Alli alone accounted for 71% of total sales.35 Insurance
coverage of weight-loss medications varies. Insurers may cover part of the cost for patients
who meet the criteria for obesity and are under a physician’s supervision.
By one estimate, sales for weight-loss medications in the U.S., Europe and Japan will reach
$3.1 billion in 2020; another estimate projects that sales will reach $10.7 billion by 2017.36,37
That number could increase if new, approved, safe medications are more effective than those
currently on the market.
Use of non-prescription weight-loss supplements is also common. A 2002 survey found that
11% of women and 6% of men used supplements in the previous year. Nearly 74% of
supplements contained stimulants — ephedra, caffeine and/or bitter orange. One in 10 users
reported using a weight-loss supplement for more than 12 months, suggesting that it is an
integral part of weight-loss strategy. Long-term use was more common in men than in
women. Unfortunately, many respondents did not talk to a healthcare provider about taking
such supplements, even though many reported they had been diagnosed with a chronic
disease (hypertension, heart disease or diabetes).38 In a 2005/2006 survey of weight-loss
supplement use, it was found that many of the users thought these products were evaluated by
the FDA for safety and effectiveness, which they were not.39
The race to develop new weight-loss drugs continues. Pharmaceutical companies are
researching a variety of compounds, such as hormones and neurotransmitters, that help to
regulate food intake and gene-food interactions For now, consumers should be aware that
weight-loss medications are not the magic bullet, have adverse effects and produce more
weight loss when used with lifestyle modifications than when used alone.40
Recent data suggests a comprehensive program of lifestyle modification including diet,
physical activity and behavioral therapy can result in a mean initial loss of 7% to 10% in the
obese.41 In addition, patients must have realistic expectations. There is no magic drug that can
help people lose all excess weight in a short period of time. It is important for healthcare
providers to educate patients on what is a reasonable amount of weight loss. Anyone who
promotes more than 20% of weight loss in less than 12 months is setting up the patients for
failure and disappointment.
Gannett Education guarantees that this educational activity is free from bias.
References
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2. Bray GA, Ryan DH. Drug treatment of the overweight patient. Gastroenterology.
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pills among U.S. adults in 1996-1998. Ann Intern Med. 2001;134(4):282-286.
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9. Seagle HM, Strain GW, Makris A, Reeves RS. Position of the American Dietetic
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10. National Association to Advance Fat Acceptance (NAAFA). Weight-loss drugs. NAAFA
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11. Rucker D, Padwal R, Li SK, Curioni C, Lau DC. Long term pharmacotherapy for obesity
and overweight: updated meta-analysis. BMJ. 2007;335(7631):1194-1199.
12. Yancy WS Jr, Westman EC, McDuffie JR, et al. A randomized trial of a lowcarbohydrate diet vs orlistat plus a low-fat diet for weight loss. Arch Intern Med.
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15. Pagotto U, Vanuzzo D, Vicennati V, Pasquali R. Pharmacological therapy of obesity. G
Ital Cardiol (Rome). 2008;9(4 Suppl 1):83S-93S.
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17. Questions and answers: orlistat and severe liver injury. U.S. Food and Drug
Administration Web site.
http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProvi
ders/ucm213040.htm. Updated May 27, 2010. Accessed August 8, 2013.
18. Hendricks EJ, Rothman RB, Greenway FL. How physician obesity specialists use drugs
to treat obesity. Obesity (Silver Spring). 2009;17(9):1730-1735.
19. Drew BS, Dixon AF, Dixon JB. Obesity management: update on orlistat. Vasc Health
Risk Manag. 2007;3(6):817-821.
20. Weissman NJ. Appetite suppressants and valvular heart disease. Am J Med Sci.
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21. Diethylpropion. Drugs.com Web site. http://www.drugs.com/cdi/diethylpropion.html.
Accessed August 8, 2013
22. Benzphetamine. Drugs.com Web site. http://www.drugs.com/cdi/benzphetamine.html.
Accessed August 8, 2013.
23. Drugs and medications: phendimetrazine tartrate cr oral uses. WebMD Web site.
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November 2012. Accessed August 8, 2013
24. New drug lorcaserin wins vote from FDA panel: panelists still cite need for continued
research on heart valve risk. WebMD Web site.
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25. FDA panel backs approval of weight loss drug lorcaserin. Time Health and Family Web
site. http://www.healthland.time.com/2012/05/11/fda-panel-backs-approval-of-weight-lossdrug-lorcaserin. Published May 11, 2012. Accessed August 8, 2013.
26. Results from phase 3 EQUATE Trial of VIVUS' Qnexa highlighted at European
Congress on Obesity. Drugs.com Web site. http://www.drugs.com/clinical_trials/resultsphase-3-equate-trial-vivus-qnexa-highlighted-european-congress-obesity-7185.html. Updated
2009. Accessed August 8, 2013.
27. VIVUS announces positive results from two phase 3 studies; obese patients on Qnexa
achieve average weight loss up to 14.7% and significant improvements in co-morbidities.
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28. Obesity pill Qsymia gains FDA approval. CBS News Web site.
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30. Zacks Equity Research. Update on Orexigen’s Contrave.
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31. James WP, Caterson ID, Coutinho W, et al. Effect of sibutramine on cardiovascular
outcomes in overweight and obese subjects. N Engl J Med. 2010;363(10):905-917.
32. Coleman E. Anorectics on trial: a half century of federal regulation of prescription
appetite suppressants. Ann Intern Med. 2005;143(5):380-385.
33. Freemark M. Pharmacotherapy of childhood obesity: an evidence-based, conceptual
approach. Diabetes Care. 2007;30(2):395-402.
34. Marketdata Enterprises Inc. The U.S. weight loss & diet control market. 11th ed. Market
Research Web site. http://www.marketresearch.com/Marketdata-Enterprises-Incv416/Weight-Loss-Diet-Control-11th-6314539/. Released May 1, 2011. Accessed August 8,
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35. Robb D. Analysis of the obesity drug markets in the US and EU: obesity research update
#5. Health Habits Web site. http://www.healthhabits.ca/2008/07/28/analysis-of-the-obesitydrug-markets-in-the-us-and-eu-obesity-research-update-5. Published July 28, 2008. Accessed
August 8, 2013.
36. The obesity drug market will increase more than six-fold over the next decade, increasing
to $2.6 billion in 2020. Fierce Biotech Web site. http://www.fiercebiotech.com/pressreleases/obesity-drug-market-will-increase-more-six-fold-over-next-decade-increasing.
Accessed August 8, 2013.
37. Global anti-obesity drugs market to reach US$10.3 billion by 2017, according to new
report by Global Industry Analysts, Inc. PRWeb Web site.
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.htm. Published November 17, 2011. Accessed August 8, 2013.
38. Blanck HM, Serdula MK, Gillespie C, et al. Use of nonprescription dietary supplements
for weight loss is common among Americans. J Am Diet Assoc. 2007;107(3):441-447.
39. Pillitteri JL, Shiffman S, Rohay JM, et al. Use of dietary supplements for weight loss in
the United States: results of a national survey. Obesity (Silver Spring). 2008;16(4):790-796.
40. Wadden TA, Berkowitz RI, Womble LG, et al. Randomized trial of lifestyle modification
and pharmacotherapy for obesity. New Engl J Med. 2005;353(20):2111-2120.
41. Vetter ML, Faulconbridge LF, Webb VL, Wadden TA. Behavioral and pharmacologic
therapies for obesity. Nat Rev Endocrinol. 2010;6(10):578-588.
Clinical Vignette
Maria, 31, is a type 2 diabetic who has struggled with obesity during her entire life. She is
5’2” and weighs 185 lb, with a BMI of 33.8. Maria has a clerical job, which keeps her at her
desk during the day. She has been unsuccessful with diet, exercise and lifestyle changes, and
is now using Orlistat (Xenical), 60 mg with each meal. Her goal is to lose excess weight and
gain better control of her diabetes. She is under the care of an endocrinologist and a
registered dietitian. After she started taking Xenical, she experienced varying levels of
adverse effects, including fatty stools; frequent, soft and often uncontrolled bowel
movements; and diarrhea.
1. How would you advise Maria to lessen the adverse effects she is experiencing?
a. Reduce the dosage of Xenical.
b. Take Xenical only before bed.
c. Eat meals that contain an even distribution of carbohydrate, protein and fat.
d. Expect the uncomfortable adverse effects.
2. Maria takes Xenical in the morning with coffee since she does not eat breakfast. What
advice do you give Maria?
a. This will help her lose weight, as Xenical needs to maintain a steady blood level.
b. She will have more uncomfortable adverse effects.
c. She should not take Xenical if she is not eating fat in a meal.
d. She should stop the medication if she refuses to eat breakfast
3. Which of the following lifestyle factors will increase Maria’s GI adverse effects?
a. Drinking alcohol
b. Smoking
c. Sedentary lifestyle
d. Fat intake of >30% calories
4. If Maria and her physician choose to try another medication, which could affect her
blood sugar adversely?
a. Benzphetamine (Didrex)
b. Phendimetrazine (Anorex)
c. Lorcaserin (Belviq)
d. Qsymia (phentermine and topiramate)
5. What warnings were recently added to the Xenical label?
a. People taking Xenical should be aware of potential signs and symptoms that could indicate
liver damage.
b. People taking Xenical should be aware of potential signs and symptoms that could indicate
kidney damage.
c. People taking Xenical should not take it for more than 12 weeks.
d. Xenical is not safe for diabetics.
Test
1. When should weight-loss medications be used?
a. Upon patient request
b. As a monotherapy
c. With patients with BMI ≥ 30, or BMI ≥ 27 to 29, if comorbidities are present
d. With all overweight type 2 diabetics
2. Proponents of drug treatment for obese people:
a. Argue that the risks of the medications outweigh the benefits
b. Suggest that medications can help “kick start” weight-loss efforts
c. Question if the relatively small weight loss attributed to the prescription is clinically
significant
d. See it as another “quick fix”
3. Which organization strongly discourages the use of weight-loss medications?
a. National Institutes of Health (NIH)
b. Food and Drug Administration (FDA)
c. Academy of Nutrition and Dietetics (AND)
d. National Association to Advance Fat Acceptance (NAAFA)
4. Obesity medications result in a _______loss of body weight.
a. 3% to 8%
c. 12% to 18%
c. Loss of more than 2 kg of weight in the first month
d. A 5% weight loss by six months
5. Which of the following weight-loss medications is the only drug approved by the FDA
for long-term use in the U.S.?
a. Sibutramine (Meridia)
b. Orlistat (Xenical)
c. Phentermine
d. Phen-fen (phentermine-fenfluramine)
6. What is the mechanism of action for orlistat (Xenical)?
a. Increases thermogenesis
b. Blocks the uptake of serotonin and norepinephrine
c. Increases insulin sensitivity
d. Inhibits pancreatic lipase
7. What warnings were recently added to the orlistat label?
a. Orlistat is not safe for diabetics.
b. People taking orlistat should be aware of potential signs and symptoms that could indicate
kidney damage.
c. People taking orlistat should not take it for more than 12 weeks.
d. People taking orlistat should be aware of potential signs and symptoms that could indicate
liver damage.
8. A client mentions that she took phen-fen for about a year. She asks you if she should
be concerned. How would you respond?
a. A year is considered short-term use, so there shouldn’t be any concern.
b. A year is considered long-term use; she should see a physician for a physical exam.
c. If it were a problem you would see symptoms; if you are asymptomatic, don’t worry.
d. The problems associated with phen-fen were overblown by the media; there is nothing to
worry about.
9. Benzphetamine is contraindicated in persons with:
a. Low blood pressure
b. Advanced atherosclerosis
c. Hypothyroidism
d. Tobacco history
10. What medication is expected to receive FDA approval in 2014 as a result of a study
initiated in June 2012 that aims to show safety data regarding patients with
cardiovascular events?
a. Contrave
b. Sibutramine
c. Qsymia (phentermine and topiramate)
d. Alli
11. What are the two weight-loss medications that gained FDA approval in 2012?
a. Sibutramine and orlistat
b. Lorcaserin and Qsymia
c. Lorcaserin and Contrave
d. Contrave and Qsymia
12. Why was Meridia removed from the U.S. market?
a. Increased risk of heart attack and stroke in patients with preexisting cardiac issues
b. Increased risk of breast tumors
c. The manufacturer ceased making the product due to materials shortages
d. Increased risk of aggressive and violent behaviors
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