Obesity is a multifactorial disorder of energy balance, in which long-term calorie intake exceeds energy output. The generally accepted benchmark is the body mass index (BMI).

1. Drugs for obesity
Dr. Nada Mohammed Abd El-latif Hamada
Lecturer of Clinical Pharmacology -Mansoura Faculty of medicine

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Learning Outcomes
By the end of the lecture, the students will be able to:
1. know treatment approaches for obesity.
2. Understand indications of medical treatment of obesity
3. List drugs approved for short-term use.
4. List drugs approved for long-term use.
5. Describe Mechanisms of action and side effects of anti-obesity
drugs.
6. Identify contraindications of anti-obesity drugs.

3. Lecture outline
1. Introduction to obesity.
2. Treatment approaches for obesity
3. Indications of pharmacotherapy
4. Drugs approved for short-term use.
5. Drugs approved for long-term use.
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Obesity is a multifactorial disorder of energy
balance, in which long-term calorie intake
exceeds energy output. The generally
accepted benchmark is the body mass index
(BMI).
The body-mass index (BMI) – (Kg/m2)
Normal: 18-25 Overweight: 25-30
Obese: >30 Morbid obesity: >40
Introduction to obesity

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 Pathophysiology:
The key factor in the development of overweight
and obesity is the imbalance that occurs
between food intake and energy expenditure.
Hormones that signal the status of fat stores (e.g.
leptin). Increasing fat storage promotes leptin
release from adipocytes.
Hormones released from the gut that convey
sensations of hunger (e.g. ghrelin), satiety
(e.g.CCK)

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 This hormonal information together with neural, gustatory, olfactory
and viscerosensory input is integrated in the hypothalamus.
 The arcuate nucleus is a key site.

8.  Leptin
 It is thought to play a key role in the regulation of body weight.
 It is produced (synthesized) by adipose tissue and acts on satiety
centers in the hypothalamus to ↓ appetite (i.e. Leptin induces satiety).
 As such when patients reach a certain peripheral fat mass, leptin acts as
a lipostat reduce food intake.
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9.  Ghrelin
 It stimulates hunger.
 It is produced mainly by the
fundus of the stomach and
pancreas.
 Ghrelin levels ↑ before meals
and ↓ after meals.
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12. Treatment approaches for obesity
The treatment goals for obesity are to:
• prevent additional weight gain.
• reduce and maintain a lower body weight.
• control related comorbid conditions.
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 Management of the obesity involves a variety of
approaches:
1. Lifestyle change (diet, exercise, behavioral therapy)
2. Pharmacotherapy.
3. Bariatric surgery.
N.B. Before initiating therapy, secondary causes of obesity
(eg, hypothyroidism and Cushing syndrome) must be
considered.
Treatment approaches for obesity

14. Indications of pharmacotherapy
1. For patients who have failed to achieve clinically significant weight
loss, defined as ≥ 5% of baseline weight after 6 months of lifestyle
interventions.
2. for individuals with BMI ≥ 30 kg/m2 or
3. BMI ≥ 27 kg/m2 with at least two comorbidities.
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 In general, drugs that have been used for obesity act either:
1. On the gastrointestinal tract, lowering nutrient absorption, or
2. Centrally, reducing food intake by decreasing appetite or increasing satiety
(appetite suppressants).
 Some of the drugs approved to treat obesity have short term indications
and the others have long term indications for usage.

16. Drugs approved for short-term use
1. Phentermine
2. Diethylpropion
 Mechanism of action:
Phentermine (Amphetamine derivatives) decreases food intake as it increases
the release of norepinephrine and dopamine by inhibitig their reuptake.
Diethylpropion has the same effect on norepinephrine.
 Tolerance to their effect develops within weeks.
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17. Adverse effects:
These drugs are classified as controlled substances due to
potential for dependence and abuse.
Dry mouth
Constipation
Insomnia
HR &BP may be increased
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18. Drugs approved for Long-term use
1. Orlistat (Xenical®)
2. Liraglutide(Saxenda®)
3. Phentermine-topiramate (Qsymia®)
4. Naltrexone/bupropion (Contrave®)
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19. 1. Orlistat (Xenical®)
 Orlistat is a pancreatic lipase inhibitor. It inhibits digestion and
absorption of dietary fats leading to weight loss.
 Orlistat is normally used for <1 year. Patients fail to lose at least 5% of
their bodyweight within 3 months, orlistat should be discontinued.
 Adverse effects include:
 Steatorrhea and flatulence.
 Malabsorption of fat soluble vitamins
 Contraindicated in cholestasis and malabsorption syndrome. 19

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2. Liraglutide(Saxenda®)
 It is an injectable long acting glucagon-like peptide-1 receptor agonist,
binding to the same receptors as does the endogenous hormone GLP-1 that
stimulates insulin secretion.
 It is developed principally for treatment of type 2 DM.
 In 2015, it was approved for treatment of morbid obesity in adults.

22. 3. Phentermine-topiramate (Qsymia®)
 Phentermine (mentioned before)
 Topiramate is an antiepileptic drug whose exact mechanism of action is
unknown. It is thought to increase satiety and suppress appetite through
multiple pathways.
 Common adverse reactions include :
 paresthesias, dizziness, suicidal ideation, insomnia, constipation, and dry
mouth.
 Topiramate is associated with birth defects so this combination is
contraindicated during pregnancy. 22

23. 4. Naltrexone/bupropion (Contrave®)
 The exact mechanisms of this opioid antagonist/antidepressant combination
product decreases food intake and weight are not fully known.
 Naltrexone may act by blocking mu receptor in appetite regulating centre.
 Bupropion may reduce activity of dopamine- mediated reward system.
 Common adverse reactions include: nausea, constipation, headache,
vomiting, dizziness, and insomnia.
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24. Examples of drugs withdrawn from market
A number of pharmacological agents that have been marketed for obesity
have been withdrawn because of concerns about safety e.g.
1. Sibutramine (Meridia®): It has been withdrawn in 2010 from the USA
due to an increased risk of cardiovascular events.
2. Lorcaserin (Belviq®): It has been withdrawn in 2020 due to an increased
risk of cancer.
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25. Finally, take home message
Think healthy behave healthy eat healthy
be happy
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26. References
• Rang & Dale's Pharmacology, 10th Edition
[ClinicalKeyStudent].
Retrieved from:
https://www.clinicalkey.com/student/content/toc/3-
s2.0-C20200033281
• Lippincott illustrated reviews: pharmacology. 6th
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