PHARMACOTHERAPY

OF OBESITY
 By:
dr. Asmaa Magdy Abdelraof
lecturer of public health at faculty of medicine,
Beni-Suef University.
Clinical nutrition consultant.
• Defining Obesity
• “The excess accumulation of fat(adipose tissue) throughout the body”
• Male : 12- 18% , > 22%
• Female : 20 – 30% , > 32%
 GUIDE FOR SELECTING OBESITY
TREATMENT

BMI Category (kg/m2)

Treatment 25-26.9 27-29.9 30-34.9 35-39.9 >40

Diet, + + + + +
Exercise,
Behavior
Tx
Pharmaco With co- + + +
-therapy morbiditie
s
Surgery With co- +
morbiditie
 Goals of therapy

◼ The ideal outcome is a return to normal bodyweight, but this is unrealistic.

◼ Effective therapy:
• Weight loss > 2 kg during the 1st month
• Weight loss > 5% below baseline by 3 to 6 months
• Remain at this level
◼ Weight loss of 10 – 15 % : very good response.
◼ Weight loss > 15% : Excellent response
Treatment Goals

• ◼ Reduce body weight.

• ◼ Prevent further weight gain (minimum goal).
• ◼ Maintain lower body weight in the longterm.
 ◼ Each medication is
associated with variation in
response. None produces
excellent weight loss in
every patient.
 It is important for practitioners to know
that the intensity of lifestyle intervention
diet and physical activity greatly affects total
weight loss.
◼ Remember that these medications can have targeted effects on outcomes
independent of weight loss. So weight loss efficacy is only one reason to choose a
particular medication. Additional health benefits might accrue independent of
weight loss decrease blood pressure ,improved lipid profile and so on.
◼ Not all medications work in every patient. We need to evaluate
for efficacy after 12-16 weeks.
◼ As with any medication, if there is not a satisfactory response,
these medications should be stopped.
◼ But when satisfactory weight loss occurs and then plateaus,
this is not a sign of tolerance or loss of efficacy.
◼ In clinical trials, when the drug is withdrawn, weight
regain occurs. Maintenance of lost weight is a sign of
success. To promote long-term weight loss maintenance

◼ Assess efficacy and safety monthly for the first three

months, then every three months thereafter.

◼ At three months, if loss is 5% or more, continue. If not,

discontinue and seek alternative approaches
◼ Despite the recognition that moderate weight loss is
beneficial and may be more easily achievable, patients
usually have self-defined goal weights that are considerably
higher. Therefore, health professionals need to encourage
their patients to target more realistic initial weight loss goals.
◼ In general, weight loss after age 65 is not
advised; actuarial tables show no benefit and
possible harm due to loss of LBM. In fact, in
the obese older adult, sarcopenia (loss of
muscle mass) is the strongest predictor of
disability and inability to perform daily
activities. A BMI below 23 is considered
below desirable in older adults .
Many anti-obesity drugs have been withdrawn
because of poor efficacy and/or severe side
effects :
• Amphetamines : high risk of dependence
• Fenfluramine : in 1997 risk of pulmonary hypertension and
valvular heart disease
• β3 adrenergic agonists : poor efficacy and sympathetic side effects
• Thyroxine : adverse effects including cardiac arrhythmias.
• Rimonabant : in 2008, risk of depression, psychosis
• Sibutramine : in 2010 due to cardiovascular safety concerns
Non prescription
Weight Loss
Products
 Product Claim Effective Safety
Blocks absorption of Ineffective for weight Possibly safe, may cause
Chitosan dietary fat loss bloating
Increases calories burned, Insufficient reliable Likely safe
Chromium decreases appetite, and evidence to rate
builds muscle
Conjugated Reduces body fat and Ineffective for weight Possibly safe
builds muscle loss
linoleic acid(CLA)
Decreases appetite and Possibly effective Unsafe due to
Ephedra (Ma
increases fat burned cardiovascular risk and
Huang) banned by FDA
Green tea extract Increases calorie and fat Ineffective for weight Possibly safe
metabolism and loss
decreases appetite
Raspberry ketones Increases lipolysis Insufficient reliable Likely unsafe especially
evidence to rate for hypertension
Garcinia cambogia Blocks enzymes in body Ineffective for weight Reports of liver
which convert glucose to loss damageassociated
fat. Also increases
serotonin in brain,
limiting appetite and
providing extra energy
Five long-term weight loss drugs were listed as
approved by the FDA for non-syndromic
obesity:

Orlistat (Xenical) (FDA 1999).

Phentermine-topiramate (Qsymia) (FDA
2012).
Naltrexone-bupropion (Contrave) (FDA
2014).
Liraglutide (GLP-1 once daily) (FDA 2014).
Semaglutide injection (GLP-1 once weekly)
(FDA2021).
 Weight Loss Drug Approved For How It Works Common Side Effects
Stomach pain, gas,
diarrhea, and leakage
of
oily stools Lowered
Inhibits fat-
gastrointestinal soluble vitamin
lipase, which reduces absorption;
Orlistat Sold as the supplements
Xenical by Xenical: adults and amount of fat are typically
prescription; over- children ages 12 and absorbed recommended and
The counter version older from food by should
sold as Alli: adults only approximately 1/3— be taken >2 hours
Alli up to apart
150 to 200 calories from drug Note: Rare
less cases of severe liver
per day injury
reported. Should not
be
taken with
Precautions:
◼ First, orlistat. This is a remarkably safe drug and is available over
the counter .
◼ You must be aware that if the patient is not absorbing fat, that patient
is not absorbing fat-soluble vitamins, and it is generally
recommended that patients take a multi-vitamin with this drug.
◼ The drug should not be prescribed to patients with chronic
malabsorption.
◼ There are increased cases of gall bladder disease associated with
orlistat and the weight loss that it produces.
◼ Finally, rare cases of liver failure have been reported in patients
taking orlistat.
Mechanism of action: GLP-1 receptor agonist
 given by injection and requires dose titration. Inject subcutaneously
in the arm, thigh or abdomen at any time of day. It comes in a pen
with a dial. Start at 0.6 mg and increase weekly by 0.6 mg. The
second week dose is 1.2 mg, the third 1.8 mg, the fourth 2.4 mg,
and the fifth week is 3 mg. You may slow the weekly titration if the
patient is experiencing GI (gastrointestinal) side effects.

 Common side effects including nausea , abdominal pain, dyspepsia,

constipation or diarrhea and headache.
Precautions:
1- should not be prescribed to patients with a personal or family history of
medullary thyroid carcinoma or
multiple endocrine neoplasia type 2. Liraglutide, and all GLP-1 receptor
agonists, cause medullary thyroid tumors
in rodents. The relationship to human thyroid cancer is unknown.

2-The GLP-1 receptor agonists, as a class, are associated with increased

risk of pancreatitis, as is liraglutide, and it
should not be given to patients with a history of pancreatitis. If patients get
pancreatitis while on liraglutide, of course you should stop the drug and not
restart it.

3-There are increased cases of gall bladder disease in the Phase 3 studies of
liraglutide for weight management,
at a slightly greater rate than that which could be explained by weight loss
alone.
4- Hypoglycemia can occur with liraglutide-induced weight loss, especially
in diabetic patients taking insulin secretagogues.

5- There are more reports of suicidal ideation in liraglutide-treated

patients than placebo in the weight loss studies, but the numbers were very
small.

6-The GLP-1 receptor agonists are associated with increased risk of renal
failure, thought to be associated with nausea, vomiting and dehydration.

7-GLP-1 receptor agonists are associated with increases in heart rate, on

average 1-2 beats per minute, of uncertain significance
Efficacy: The large response of semaglutide on weight loss from
baseline is greater than other anti-obesity therapies and could be
comparable to certain types of bariatric procedures.

Safety: In STEP 8, rates of AEs (which were mostly GI- related) were
similar with semaglutide 2.4 mg and
liraglutide 3.0 mg (95.2%vs. 96.1%). Of note, rates of discontinuation
due to of AEs were lower with
semaglutide than with liraglutide.
The occurrence of cholelithiasis was consistent with the known associations
between rapid weight loss and increased risk of cholelithiasis, and with
previous reports of gall bladder related disorders with GLP-1RAs.
There were no notable increases in the incidence of acute pancreatitis with
semaglutide 2.4 mg.
In terms of AEs, diabetic retinopathy events were reported in 4.0% of
patients receiving semaglutide 2.4 mg, 2.7% with semaglutide 1.0 mg and
2.7% with placebo.

semaglutide has restrictions for some patient populations, such as:

⬢ Those with personal or family history of medullary thyroid carcinoma.
⬢ Caution should be utilized for those with gastroparesis.
⬢ An individual has a history of acute pancreatitis, semaglutide should not
be used and should be discontinued if a patient develops acute pancreatitis
after initiation.
The medication stimulates 5-HT2C receptors on the pro-opiomelanocortin (POMC) neurons in
the arcuate nucleus; this causes the release of alpha-melanocortin-stimulating hormone (alpha-
MSH), which acts on melanocortin-4 receptors in the paraventricular nucleus to suppress appetite.
Weight Loss Adults Approved How It Works Common Side Effects
Drug For
Lorcaserin Adults Acts on the Headaches, dizziness,
Sold as serotonin feeling tired, nausea,
Belviq receptors in the dry mouth, cough,
brain. This may and constipation.
help you eat less Should not be taken
and feel full after with selective
eating smaller serotonin reuptake
amounts of food. inhibitors (SSRIs)
and monoamine
oxidase inhibitor
(MAOI) medications
◼ Dose 10 mg twice daily oral.
◼ Belviq is a selective 5-HT2C receptor agonist. 5-HT2C receptors are
located almost exclusively in the brain and can be found in the
hypothalamus where appetite is controlled.
The activation of 5-HT2C receptors in the hypothalamus increases
proopiomelanocortin (POMC) production and, consequently, promotes
weight loss through satiety. While it is generally believed that 5-HT2C
receptors help to regulate appetite, as well as mood and endocrine
secretion, the exact mechanism of appetite regulation is not yet known.

Contraindications and precautions

◼ Safety data lacking for patient with depression.
◼ Unproven concern for potential cardiac valvulopathy.
◼ Contraindicated in pregnancy.
◼ Mechanism of action: bupropion inhibits dopamine and
noradrenaline reuptake while naltrexone an opioid antagonist act
to antagonize the feed back loop that limits Bupropion’s anorexic
effects.

◼ It reduce appetite with possible decrease fat absorption.

 Contraindications and precautions
1- Bupropion, being used as an antidepressant and for smoking cessation,
has been associated with
neuropsychiatric symptoms, and in younger (less than 24 years) depressed
patients, increased risk of suicidality.
Thus, the combination carries a boxed warning on its US label regarding
suicidality, and prescribers should bear this in mind when prescribing for
weight loss in younger depressed individuals.

2- Bupropion also lowers seizure threshold, and should not be given to

patients with a history of seizures.

3-Bupropion also is shown to produce increases in mean blood pressure and

pulse, especially early on in treatment when naltrexone/ bupropion is
prescribed for weight management. So, it should be monitored during the
first two weeks, especially blood pressure and pulse.
◼ The drug should not be prescribed within 14 days of taking an MAOI
(monamine oxidase inhibitor), because of the bupropion component.

4-Naltrexone is an opioid antagonist. Patients who require opioids

chronically should not take this drug.

5-Rare cases of hepatotoxicity have been associated with naltrexone,

6- Narrow-angle glaucoma may be exacerbated by bupropion.

◼ As with all weight management medications, naltrexone /
bupropion is contraindicated in pregnancy.
Dose of Contrave
Approved in the US only

◼ Mechanism of action: phentermine has Sympathomimetic effect as

increasing noradrenaline release and decrease reuptake in hypothalamic
nuclei so decrease food intake it may increase resting energy expenditure

◼ Topiramate has anticonvulsant effect(GABA receptor modulation,

carbonic anhydrase inhibition, glutamate antagonism) reduce body weight by
promoting taste aversion and decrease caloric intake.

3.75 mg phentermine/ 23mg topiramate increase dose every 2 weeks

according to tolerability.
A mix of two drugs:
phentermine (suppresses your appetite and curbs your desire to eat) and
topiramate (used to treat seizures or migraine headaches). May make you
feel full and make foods taste less appealing.

Side effects: Tingling of hands and feet, dizziness, taste alterations dysgeusia
(particularly with carbonated beverages), trouble sleeping, constipation, dry
mouth,
and increased heart rate.
Note: Sold only through certified pharmacies.
May lead to birth defects. Do not take Qsymia if you are pregnant or
planning a pregnancy
It is very important
to remember
1- Pregnancy: Obtain a negative pregnancy test before prescribing phentermine
/ topiramate ER and monthly while on therapy

2-On breast feeding: Do NOT prescribe

3- History of seizures: Naltrexone SR / bupropion SR is contraindicated.

Taper phentermine / topiramate ER slowly when discontinuing to avoid

precipitating seizure.

4- History of kidney stones: Avoid: Phentermine / topiramate ER, orlistat.

5- With glaucoma: Contraindicated: Phentermine /topiramate ER.

(Angle closure glaucoma associated with naltrexone SR / bupropion SR).

6- For hypertension: Naltrexone SR / bupropion SR and phentermine /

topiramate ER can increase blood pressure.

7- With arrhythmia: Naltrexone SR / bupropion SR, phentermine / topiramate

ER, liraglutide can all increase heart rate.
8- With depression: Naltrexone ER/bupropion ER is the recommended
drug for patients with obesity and comorbid mood disorders. However,
caution is required when using naltrexone ER/bupropion ER in patients
taking antidepressants.

◼ Although liraglutide at a high dose, resulted in mood disorders worsen

slightly. However, because there is less interaction with antidepressants,
liraglutide should be considered first for patients taking antidepressants.

◼ As phentermine/topiramate CR can cause mood disorders, it should be

avoided in patients with mood disorders.
◼ Treatment should focus on behavior and lifestyle treatment for the
entire family, including nutrition support and increased physical
activity.

◼ For children 12 and older, use of weight loss medications is

appropriate(liraglutide and orlistat)

◼ Naltrexone ER/bupropion ER in younger (less than 24 years) it

caused adverse mental and nervous system responses with increased
risk of suicidality.
◼ The recommendations for exercise from the American College of Sports
Medicine differ for weight loss versus weight maintenance. Physical
activity of fewer than 150 minutes per week has a minimal effect on
weight loss,
whereas physical activity of greater than 150 minutes per week usually
results in modest weight loss (defined
as 2 to 3 kg), and physical activity between 225 and 420 minutes per
week is likely to result in the greatest
weight loss (5 to 7.5 kg).
Thank you