2. REFERENCES
• Patel DK, Dunican KC. Obesity. In: Zeind CS, Carvalho
MG, ed. Applied Therapeutics : The Clinical Use of
Drugs. 11th ed. Philadelphia : Wolters Kluwer Health;
2018: 756-67.
• Venkatrao M, Nagarathna R, Majumdar V, Patil SS, Rathi
S, Nagendra H. Prevalence of Obesity in India and its
Neurological Implications: A multifactor analysis of a
nation-wide cross-sectional study. Annals of
Nerosciences, 2021 May 29; 27(3-4):153-61. doi:
10.1177/0972753120987465
3. • CDC official webpage
https://www.cdc.gov/obesity/
Accessed on Apr 10, 2022
• NHLBI official webpage
https://www.nhlbi.nih.gov/health/educational/wec
an/healthy-weight-basics/obesity.htm
Accessed on Apr 10, 2022
4. CONTENTS
• Introduction
• Obesity related health conditions
• Etiology and pathophysiology
Genetic factors
Hypothalamus dysregulation
Peripheral hormones regulating
eating behavior
Neurotransmitters
Medications
• Management and Treatment
Non-pharmacologic therapy
Pharmacologic therapy
Short-term therapy
Long-term therapy
Medical devices for treatment of
obesity
Surgery
Investigational agents
6. • Obesity is a chronic disease that is characterized by
excess body fat accumulation which may impair health.
• The prevalence of obesity has become an epidemic.
• Prevalence of obesity in India is 40.3%.
• Zonal variations were seen as follows: south had the
highest at 46.51% and east lowest at 32.96%.
• Obesity was higher found to be higher in females
(41.88%) than in males (38.67%).
7. • It is recognized by the World Health Organization
(WHO) and US Federal government as a growing
problem that is burdening our healthcare organizations
and economy.
• Analyses estimate the total annual US economic costs
associated with obesity are in excess of $215 billion
with worldwide impact to be around $2 trillion.
8. • Overweight and obesity are defined by body mass
index (BMI), a measure of weight in relation to
height.
• BMI is calculated as weight (in kg) divided by
height (in metre) squared.
9. Weight status BMI
Underweight <18.5
Normal ≥18.5 to <25
Overweight ≥25 to <30
Obesity ≥30
Obesity class BMI
I ≥30 to <35
II ≥35 to <40
III ≥40
10. • Measurement of waist circumference is used
to access for increased abdominal fat
accumulation and to determine health risk.
• Waist circumference greater than 40 inches (or
102 cm) in males and 35 inches (or 88 cm) in
females are associated with increased risk of
metabolic diseases.
11. • The waist-to-hip ratio can also be used to assess
the risk of obesity related disorders.
• A waist-to-hip ratio of >1 in males and >0.8 in
females indicates high intra-abdominal fat.
• It is superior to both BMI and waist circumference
in determining obesity related cardiometabolic
risk.
12. QUES1: S.B. is a 48 year old female, her height is 168
cm, current weight is 91 kg and waist circumference is
96 cm. How is obesity assessed in a patient like S.B.? Is
she obese?
ANS: The preferred method to assess obesity is to
measure BMI. Measurement of WC will aid in estimating
the risk of obesity related comorbidities.
• S.B.’s BMI is 32.2 which is obesity class I.
• Her WC is more than 88 cm which predisposes her to
an increased risk of obesity related comorbidities.
15. • Genetic factors:
• The study by Wardle et al has demonstrated the
heritability estimate of 77% for BMI, 76% for waist
circumference and 60% for waist-to-hip ratio.
• In mice, it was observed that they became obese as a
result of mutations in certain genes. Some of these
have now been characterized, including the ob
(obesity), tub (tubby), fat and db (diabetes) genes.
• Mice that are homozygous for mutant forms of these
genes – ob/ob mice and db/db mice – eat excessively,
have low energy expenditure, become grossly fat and
have numerous metabolic and other abnormalities.
16. • Hypothalamus dysregulation:
• At the beginning of the 20th century it was observed
that patients with damage to the hypothalamus tended
to gain weight.
• In the 1940s, it was also shown that discrete lesions in
the hypothalamus of rodents caused them to become
obese or exhibit unusual feeding behavior.
• Hypothalamus plays a key role in body weight
regulation by controlling satiety, hunger and in turn
food intake.
17. • Although other sites in the brain such as the nucleus
accumbens, the amygdala and the nucleus tractus
solitarius (NTS) are also crucial.
• Within the hypothalamus, the arcuate nucleus, situated in
the floor of the third ventricle, is a key site.
• It receives input from peripheral satiety sites (e.g.,
gastric and pancreatic peptides released secondary to
food passing through GIT), leptin released by adipocytes,
and from the catecholamine neurotransmitter system in
the brain.
• It also has extensive reciprocal connections with other
parts of the hypothalamus involved in monitoring energy
status, in particular the paraventricular nuclei and the
18. • Neuropeptides:
• Appetite is regulated in part via orexigenic
neuropeptides (namely, Neuropeptide Y and Agouti
related peptide) which signal hunger and
anorexigenic neuropeptides (namely, α-MSH) which
signal satiety within the hypothalamus.
• POMC (pro-opiomelanocortin) is a precursor protein
to α-MSH (α-melanocyte stimulating hormone).
• α-MSH binds to melanocortin-3 and melanocortin-4
receptors to suppress appetite.
• Research on melanocortin-4 receptor agonists is
ongoing, but trials with melanocortin-3 receptors
agonists have failed to suppress feeding.
19. • Peripheral hormones regulating eating behavior:
• Ghrelin:
• Released from stomach before meals.
• Increases appetite via stimulation of neuropeptide
Y and Agouti related peptide.
• Peptide tyrosine tyrosine (peptide YY) and
pancreatic polypeptide:
• Released from pancreas and act as appetite
suppressant.
20. • Amylin:
• Pancreatic hormone released in response to
eating and functions as anorectic hormone.
• GLP-1:
• Secreted from gut in response to food intake and
works to reduce food intake.
• Cholecystokinin:
• Secreted from small intestines in response to
food intake and works to reduce food intake.
21. • Nesfatin-1:
• An 82 amino acid peptide derived from a precursor
molecule nucleobindin 2.
• Produced by many central and peripheral tissues
like hypothalamus, GIT and adipose tissue.
• Decrease appetite by inhibiting orexigenic NPY
neurons.
22. • Leptin:
• It is a protein synthesized by adipocytes which acts
on receptors of hypothalamus to act as an afferent
satiety signal in the brain.
• It reduces the food intake, body fat and weight by
reducing NPY activity.
• Leptin and leptin-like products have been
investigated for promotion of weight loss, but leptin
resistance impedes its clinical utility.
23. • Neurotransmitters:
• Serotonin:
• Serotonin acts an appetite suppressant by stimulating
serotonin 2C (5-HT2C) receptors on the anorexigenic
neurons (POMC) in the arcuate nucleus of
hypothalamus.
• Dopamine:
• Agents that increase dopamine activity (e.g.,
apomorhine, a dopamine agonist; levodopa, a
metabolic precursor of dopamine; amphetamine, a
stimulator of release of dopamine from presynaptic
stores) have been shown to have an anorexic effect.
24. Associated with
weight loss
Associated with
minimal weight
gain or weight
neutral
Associated with
weight gain
Glucose-
lowering
Biguanides
(Metformin)
GLP-1
analogues
(albiglutide/
dulaglutide/
exenatide/
liraglutide/
lixisenatide)
SGLT-2
inhibitors
(canagliflozin/
dapagliflozin/
empagliflozin/
ertugliflozin)
Amylin
analogues
α-glucosidase
inhibitors
(acarbose,
miglitol &
voglibose)
DPP-4
inhibitors
(alogliptin/
linagliptin/
saxagliptin/
sitagliptin/
vildagliptin)
Insulin
Sulfonylureas
(esp. Glyburide)
Meglitinides
(repaglinide &
nateglinide)
Thiazolidinedio
nes
(rosiglitazone &
pioglitazone)
Common drugs and their effect on weight
25. Associated with
weight loss
Associated with
minimal weight
gain or weight
neutral
Associated with
weight gain
Antipsychotics Quetiapine,
aripiprazole,
ziprasidone
Clozapine,
olanzapine,
risperidone
Antidepressants NDRI (Bupropion) Fluoxetine,
imipramine
MAOIs, TCAs,
SNRIs (venlafaxine
& duloxetine)
paroxetine,
fluvoxamine,
mirtazapine
Antiepileptics Topiramate,
zonisamide,
felbamate
Lamotrigine Valproate,
vigabatrin,
gabapentin,
pregabalin,
carbamazepine
26. Associated with
weight loss
Associated with
minimal weight
gain or weight
neutral
Associated with
weight gain
Antihypertensiv
es
ACEI, ARBs,
CCBs
β-blockers (esp.
propranolol),
α-blockers
(prazosin,
terazosin)
Anti-
inflammatory
NSAIDs,
DMARDs
Corticosteroids
Antihistamines 2nd generation 1st generation
Contraceptives Barrier
methods,
OCPs
Injectables (esp.
medroxyprogester
one)
28. • Obesity is a chronic disease that requires life-long
efforts for successful treatment.
• The goals of weight loss and management are to
prevent weight gain, reduce body weight and maintain
weight loss over a long period of time.
• Weight loss is recommended for patients who have
obesity (i.e. BMI ≥30 kg/m2) or are overweight (i.e. BMI
≥25 kg/m2) with an obesity related comorbid
condition or have an increased waist circumference.
29. • An appropriate initial goal for weight loss is 5-
10% of the baseline body weight within 6 months.
• The initial treatment plan must include reduced
calorie diet, increased physical exercise, and
behavioural modifications.
• These non-pharmacologic measures must be
attempted and maintained for at least 6 months
before considering pharmacotherapy.
31. • Diet:
• Caloric recommendations for women seeking to loose
weight are 1200-1500 kcal/day and 1500-1800
kcal/day for men alternatively a deficit of 500-750
kcal/day is associated with weight loss.
• Exercise:
• Increased physical activity will contribute to negative
energy balance that is needed for weight loss.
• Overweights should have at least 30 min of
moderate-intensity exercise daily.
32. • Behavior therapy:
• Frequent individual or group counselling sessions
(>14 per month) with a trained interventionist
(registered dietician, nutrition counsellor, exercise
specialist, health counsellor, psychologist or other
trained professional).
33. QUES2: S.B. states that she has been overweight since she
was a toddler. She reports that she never received dietary
counselling from a medical professional and has always
dieted on her own by restricting fat intake. She expresses
a desire for weight loss therapy. What are appropriate
goals for S.B.’s weight loss? What should the initial
treatment plan include?
ANS: An appropriate initial goal for weight loss is 5-10%
of the baseline body weight within 6 months. So
appropriate goal for S.B. is to lose 4.55-9.1 kg within 6
months.
The initial treatment plan must include reduced calorie
diet (1200-1500 kcal/day), moderate intensity physical
35. • Obesity is a chronic, life-long illness that may require long-
term medication therapy.
• Medication should only be considered for patients with BMI
≥30 kg/m2 without risk factors or BMI ≥27 kg/m2 with an
obesity related comorbid condition like hypertension, type 2
diabetes, obstructive sleep apnea, dyslipidemia, etc.
• Medications should not be considered as replacement for
diet, exercise and behavioural modification but rather as
adjunctive therapy.
• Currently marketed anti-obesity drugs act by suppressing
appetite or by reducing fat absorption.
37. • FDA has approved several weight loss drugs for short
term use defined as <12 weeks.
• These include:
Phentermine
Phendimetrazine
Benzphetamine
Diethylpropion
• Of these agents, phentermine is most commonly
prescribed and is frequently prescribed, off-label, for
long-term therapy.
38. • Phentermine is approved for adjunctive therapy in patients
older than 16 years of age, at a dosage of 18.75 to 37.5 mg
taken 2 hours after breakfast.
• Most common adverse effects associated with phentermine
are dry mouth and insomnia.
• Phentermine is also associated with risk of developing
cardiovascular diseases and pulmonary hypertension and is
therefore contraindicated in patients with cardiovascular
diseases and hypertension.
• It has an abuse potential and is considered as schedule IV
drug which further limits its use as a weight loss agent.
39. • Diethylpropion, phendimetrazine and benzphetamine
exhibit appetite suppressing effects similar to
phentermine but are less widely prescribed.
• They also share adverse effects and contraindications
similar to phentermine.
• The abuse potential with drugs is high, with
diethylpropion classified as schedule IV drug and
benzphetamine and phendimetrazine classified as
schedule III drugs.
40. QUES 3: S.B. returns to her physician for follow-up 6 months
later. She has managed to lose 7 kg and is at a weight of 84 kg.
based on her BMI of 29.8 kg/m2 , her weight is classified as
overweight. She also has a medical history of hypertension,
sleep apnea, osteoarthritis, and depression. Her current
medications include hydrochlorthiazide, metoprolol, naproxen
and bupropion. Although she has achieved her goal with 7.7%
weight loss, she is disappointed as her weight loss has
plateaued. She still wants to lose additional weight. She asks the
physician about short-term anti-obesity medications that can
help accelerate her weight loss. Would a short-term agent be
appropriate for S.B.?
ANS: No. S.B.’s physician should not prescribe a short-term
weight loss medication to S.B. as they are contraindicated in
hypertensive patients. Also, short-term agents will not provide
42. Drug Dosing
Orlistat 60-120 mg PO TID
Lorcaserin 10 mg PO BD
Liraglutide 0.6 mg SC daily x 1 week increase
dose by 0.6 mg weekly until
therapeutic dose of 3 mg daily
Phentermine/Topiramate 3.75/23 mg PO QAM x 2 weeks
then 7.5/46 mg PO QAM x 12
weeks. Then evaluate weight loss,
if less than 3% dose may be
titrated to 11.25/ 69 mg PO QAM
x 2 weeks then 15/92 mg PO
QAM.
Naltrexone/Bupropion 8/90 mg PO QAM x 1 week then
8/90 mg PO BD x 1 week then
16/180 mg PO QAM and 8/90 mg
PO QPM X 1 week then 16/180 mg
PO BD.
43. ORLISTAT
• Orlistat is FDA approved drug for the long term
management of obesity as an adjunct to lifestyle
modifications.
• It inhibits the dietary fat absorption by inhibiting
the GI (both gastric and pancreatic) lipase
activity.
• This results in excretion of 30% of ingested fats
in feces.
44. • Orlistat has no systemic absorption, no CNS effects
and no appetite suppressant effects.
• The therapeutic activity of orlistat takes place in
stomach and small intestine and effects are seen as
soon as 24-48 hours after dosing.
45. • Adverse effects:
• The most common side effects associated
with orlistat are GI problems:
• Loose/fatty/oily stools
• Oily spotting
• Increased defecation frequency
• Fecal urgency
• Fecal incontinence
• Flatus with discharge
• Bloating
• Cramping
46. • As GI adverse effects are worse with the high fat
diet, orlistat may enhance the dietary
compliance with low fat diet.
• The most common non-GI side effect is
headache observed in 6% patients receiving
orlistat.
• Rare cases of oxalate induced acute kidney
injury and liver injury have also been reported
with the use of orlistat.
47. • Orlistat may reduce the absorption of fat soluble
vitamins (A, D, E, K) and the patient on orlistat should
take a multivitamin supplement, that contains these
vitamins, once a day at least 2 hours before or after the
administration of orlistat.
• Orlistat may also reduce the absorption of lipophilic
drugs including amiodarone, valproate, lamotrigine,
cyclosporine.
• It is contraindicated in pregnancy and in patients with
chronic malabsorption syndrome and cholestasis.
48. LORCASERIN
• Lorcaserin is FDA approved drug for long term obesity
management as an adjunct to lifestyle modification.
• It is selective serotonin 2C (5-HT2C) receptor agonist.
• It promotes the feeling of satiety by activating 5-HT2C
receptors on the anorexigenic proopiomelanocortin
neurons in the hypothalamus.
49. • Lorcaserin is available as 10 mg tablets and is
dosed at 10 mg twice daily.
• If the patient does not experience >5% weight loss
after 12 weeks of therapy, the drug should be
discontinued.
• The efficacy of lorcaserin has been demonstrated in
three phase 3 clinical trials: BLOOM, BLOSSOM and
BLOOM-DM.
• Lorcaserin was shown to produce an average
weight loss of 5.8% of initial weight after 1 year and
7.2% after 2 years.
50. • The most common adverse effects associated with
lorcaserin in patients without diabetes are:
• Dizziness
• Fatigue
• Headache
• Nausea
• Dry mouth
• Constipation
51. • In patients with diabetes the most common adverse
effects are:
• Headache
• Back pain
• Fatigue
• Hypoglycemia
• Cough
53. • In the past non-selective serotonergic agonists
(fenfluramine and dexfenfluramine) were withdrawn
from the market due to adverse cardiac events,
especially valvulopathy.
• Locaserin has not been shown to predispose the
patient to develop valvulopathy.
• Based on the serotonergic activity of lorcaserin, it is
advised to avoid lorcaserin with other serotonergic
drugs such as SSRI, SNRI, MAO inhibitors and
triptans.
54. • Lorcaserin is an inhibitor of CYP2D6, so caution should
be used when co-administering lorcaserin with drugs
metabolized by this enzyme.
• The use of dextromethorphan is of particular concern
because it is metabolized by CYP2D6 and may have
serotonergic effects.
• Lorcaserin is contraindicated in pregnancy.
55. LIRAGLUTIDE
• Liraglutide is FDA approved injectable medication for
long term obesity management as an adjunct to
lifestyle modification.
• It is glucagon-like peptide-1 (GLP-1) receptor
agonist.
• Activation of GLP-1 receptor in CNS promotes the
feeling of satiety, thereby reducing food intake.
56. • If the patient has not produced ≥4% weight loss by
16 weeks of therapy, the drug must be
discontinued.
• The efficacy of liraglutide has been demonstrated
in three phase 3 clinical trials: SCALE Maintenance,
SCALE Obesity and Pre-Diabetes, and SCALE
Diabetes.
• The results of SCALE Maintenance trial indicate
that by 12 weeks of therapy, liraglutide produces
an average weight loss of 6% greater than placebo;
in other 2 trials it has produced 3.9-5.4% weight
loss after 56 weeks of therapy.
57. • The most common adverse effects associated with
liraglutide are:
• Nausea/Vomiting
• Diarrhea
• Constipation
• Dizziness
• Dyspepsia
• Headache
• Abdominal pain
• Hypoglcemia
• Fatigue
• Decreased apetite
• Increased lipase
58. • In order to reduce the GI side effects, liraglutide is
initiated at doses of 0.6 mg daily SC, with weekly
increments of 0.6 mg to reach an effective dose of 3
mg daily over a 5 week period.
• Liraglutide is associated with an increased risk of
• medullary thyroid carcinoma and
• acute pancreatitis.
• It is contraindicated in
• Pregnancy
• Hypersensitivity to liraglutide
• Personal/family history of medullary thyroid
carcinoma
• Personal/family history of multiple endocrine
59. PHENTERMINE/TOPIRAMATE ER
• Phentermine/topiramate ER is a combination drug
that has been approved by FDA for long term obesity
management as an adjunct to lifestyle modification.
• Phentermine is a sympathomimetic agent that
functions as an appetite suppressant by increasing
the concentration of norepinephrine in the CNS.
• The mechanism by which topiramate leads to weight
loss are still unknown.
60. • Dosing:
• The therapy is initiated at a dose of phentermine 3.75
mg/ topiramate 23 mg daily for 14 days, after which the
dose is increased to phentermine 7.5 mg/ topiramate 46
mg daily for 12 weeks.
• Now evaluate the weight loss if it is less than 3%, the drug
should be discontinued or the dose is escalated to
phentermine 11.25 mg/ topiramate 69 mg for 14 days
followed by phentermine 15 mg/ topiramate 92 mg for 12
weeks.
• Again evaluate the weight loss, if the patient has not
experienced the weight loss of ≥5% discontinue the drug.
61. • The efficacy of phentermine/topiramate has been
demonstrated in two phase 3 clinical trials and one
expansion trial: CONQUER, EQUIP and SEQUEL (an
extension of CONQUER trial).
• Phentermine/topiramate ER 7.5/46 mg was shown to
produce an average weight loss of 7.8% of initial
body weight after 1 year and 9.3% after 2 years.
• Phentermine/topiramate ER 15/92 mg was shown to
produce an average weight loss of 9.8% of initial
body weight after 1 year and 10.5% after 2 years.
62. • The most common adverse effects associated with
phentermine/topiramate are:
• Dizziness
• Dysgeusia
• Insomnia
• Paresthesia
• Dry mouth
• Constipation
• Birth defects, especially oral clefts if taken during the
first trimester of pregnancy.
63. • Phentermine/topiramate ER is contraindicated in
• pregnancy,
• in patients with
glaucoma,
hyperthyroidism,
MAOI use within past 14 days and
hypersensitivity to sympathomimetic amines.
64. NALTREXONE/BUPROPION
• Naltrexone/bupropion is a combination drug that has
been approved by FDA for the long term obesity
management as an adjunct to lifestyle modification.
• Bupropion, an antidepressant that inhibits
norepinephrine and dopamine reuptake, has a known
side-effect of weight loss when used for the treatment
of depression and smoking cessation.
65. • The weight loss caused by bupropion is the result of
appetite suppression induced by the stimulation of
proopiomelanocortin neurons in the hypothalamus.
• Naltrexone, an opioid receptor antagonist, enhances
this appetite suppression by blocking opioid receptors
on the same proopiomelanocortin neurons.
66. • Naltrexone/bupropion are available as combination
8/90 mg tablets.
• The treatment is initiated at a dose of 1 tablet every
morning.
• This dose is titrated over a course of 4 weeks to a dose
of 2 tablets twice daily, for a total dose of 32/360 mg.
• If the patient has not experienced a weight loss of ≥5%
after 12 weeks of therapy at the maintenance dose, the
drug should be discontinued.
67. • The efficacy of naltrexone/bupropion has been
demonstrated in four 1-year phase 3 clinical trials: COR-I,
COR-II, COR-BMOD and COR-Diabetes.
• Naltrexone/bupropion 32/360 mg has shown to produce
an average weight loss of 6.1% to 6.4% of initial body
weight.
• When couple with intensive behaviour modification, the
patients experienced an average weight reduction of 9.3%
of initial body weight.
68. • The most common adverse effects associated with
naltrexone/bupropion are:
• Nausea/vomiting
• Constipation
• Diarrhea
• Headache
• Insomnia
• Dry mouth
• Slight increase in blood pressure and heart rate have
also been reported in phase 3 clinical trials, thus these
parameters should be monitored during therapy
• FDA has approved black box warning for suicidal
thoughts and behaviour
69. • Bupropion is an inhibitor of CYP 2D6; so caution should be
used when co-administering naltrexone/bupropion with
drugs metabolized by CYP2D6.
• It is contraindicated in:
• Pregnancy
• Uncontrolled hypertension
• Seizure disorders
• Anorexia nervosa/ bulimia nervosa
• Sudden discontinuation of alcohol, barbiturates,
benzodiazepines, antiepileptic drugs
• Chronic opioid use
• Use of MAOI within 14 days
• Patients currently taking any other bupropion containing
products
70. QUES 4: S.B. realizes that her obesity is a chronic condition
and inquires about long-term therapy for weight loss. What
options are available for long term maintenance of obesity in
case of S.B.?
Ans: As S.B. is a known case of HTN, so she should not be
prescribed phentermine/topiramate and
naltrexone/bupropion as they will exacerbate her
hypertension. Also, she is already taking bupropion which
will duplicate with naltrexone/bupropion and may cause
serotonin syndrome with lorcaserin.
So, orlistat and liraglutide are two available options for her
of which she could choose the most appropriate agent based
71. Supplement Proposed mechanism Adverse effects
Chitosan A cellulose type polysaccharide
reported to bind dietary fat and
prevents absorption
Bloating, constipation,
diarrhea, flatulence,
heartburn, nausea.
Should be avoided in
patients with shellfish
allergy.
Caffeine Increased thermogenesis by inhibiting
breakdown of cAMP
Insomnia, tachycardia,
irritability, anxiety
Green tea Polyphenols and caffeine act
synergistically to reduce fat absorption
and lipogenesis, and cause
thermogenesis
Insomnia, tachycardia,
irritability, anxiety,
Reports of
hepatotoxicity
Guarana
(Brazilian cocoa,
Paullinia cupana)
Seeds contain 2.5-7% caffeine which
enhance thermogenesis
Insomnia, anxiety,
irritability, tachycardia
Yerba mate
(Ilex
paraguariensis)
Yerba mate is a herbal tea made from
leaves of ilex paraguariensis containing
caffeine
Insomnia, anxiety,
irritability, tachycardia
Dietary supplements for weight
loss
72. Glucomannan
(Konjac)
Prevents fat absorption and
prolongs/promotes the satiety
Bloating, flatulence,
nausea
Hydroxycitric acid
(Garcinia cambogia)
Acts by:
i- Competitive inhibition of ATP citrate
lyase enzyme involved in fat synthesis
ii- Increasing the release or availability
of serotonin in the brain causing
appetite suppression
Reports of
hepatotoxicity,
rhabdomyolysis, may
inhibit platelet
aggregation.
Hoodia Appetite suppressant Unknown
Citrus aurantium
(bitter orange,
Seville orange, sour
orange)
Contains synephrine (structurally
similar to epinephrine)
Increased BP and HR
Reports of angina,
increased QT interval,
seizures, ischemic
colitis.
Inhibits CYP 3A4
leading to drug
interactions.
73. QUES 5: S.B. began long-term therapy with orlistat 120 mg
and lost an additional kg in 6 months. After 6 months, S.B.’s
weight loss began to taper and she regained 2 kg such that
1 year later her total net weight loss is 6 kg. S.B.’s current
weight is 78 kg but she is disappointed that she has
regained weight and inquires about dietary supplements for
weight loss. How would you advise S.B. with regard to
dietary supplements?
ANS: Numerous dietary supplements for weight loss are
available in the market. But reliable data on efficacy of these
agents is limited and safety data are lacking. Clinical data do
not support the use of these agents. So, S.B. should be
advised against the use of dietary supplements for weight
74. QUES 6: S.B. was no longer able to continue orlistat and she
slowly regained the lost weight. Two years after discontinuing
orlistat, she regained 7 kg. her current weight is 85 kg. she is
frustrated that she has regained weight despite compliance
with comprehensive lifestyle interventions. She asks whether
her results are usual?
ANS: S.B.’s weight regain after discontinuing orlistat is typical.
Trials have shown that weight loss achieved with anti-obesity
drugs is unlikely to be sustained after discontinuation. Weight
regain is expected as the underlying pathology of obesity is
unchanged.
75. MEDICAL DEVICES FOR TREATMENT OF
OBESITY
• A device called as the vBloc Maestro Rechargeable
System has recently been approved by FDA as a
treatment option for patients with extreme obesity
(BMI ≥ 40 kg/m2 or ≥ 35 kg/m2 with comorbid
conditions) who have failed to survive atleast one
supervised weight management program within the
past 5 years.
• The device is surgically implanted into the abdomen
where it emits intermittent electrical pulses to block
the signalling by vagus nerve.
76. • In a recent randomized, double-blind, sham
controlled clinical trial, the vBloc system produced a
weight loss of 9.2% of initial body weight, compared
to a weight loss of 6.0% with the sham technology.
• The most common adverse effects are heartburn,
dyspepsia and abdominal pain.
77. QUES 7: Is S.B. a candidate for implantable medical device?
ANS: S.B.’s current weight is 85 kg and height is 168 cm.
Her BMI is 30.1 kg/m2 which is below the threshold for use
of vBloc. So, she is not a candidate for medical device at
this time.
78. SURGERY
• Surgery may be an option for individuals with extreme
obesity (BMI ≥ 40 kg/m2 or ≥ 35 kg/m2 with comorbid
conditions) who have not responded to lifestyle changes
with or without adjunctive pharmacotherapy.
• For severely obese individuals (>100% more than the
normal body weight), the most effective treatment is a
surgical procedure.
79. • Bariatric surgical procedures either reduce the absorptive surface
of the GIT resulting in malabsorption and/or reduce the stomach
volume so that the person feels full after a small meal.
• Examples:
• Roux-en-Y gastric bypass
• Gastric banding
• Vertical banded gastroplasty
• Biliopancreatic diversion
82. • Gastric bypass has shown to produce a greater weight
loss.
• Mortality rate from bariatric surgery is estimated to be
0.3-1.9%.
• Complications of bariatric surgery include nausea,
stomach ulceration, stenosis, anemia and cholelithiasis.
• Medications such as NSAIDs and bisphosphonates may
cause ulceration and should be avoided.
• Medications that are extended release or delayed
release may not be absorbed owing to changes in
gastric size.
• Medications may need to be administered using liquid
83. Ques 8: S.B. returns to her physician 3 years later. She has gained an
additional 16 kg and her BMI now is 35.4 kg/m2. She reports inability
to maintain her weight with diet and exercise therapy. Lab tests
provide following results:
BP: 154/92 mg Hg
Total cholesterol: 400 mg/dL
TG: 320 mg/dL
HDL: 30 mg/dL
LDL: 260 mg/dL
Is S.B. a candidate for bariatric surgery? What advise will you give
her?
ANS: Although S.B. is a candidate for bariatric surgery based on her
BMI of 35.4 kg/m2 and her comorbid conditions (HTN, obstructive
sleep apnea, osteoarthritis and depression) but its better to consider
alternative pharmacotherapeutic options. S.B.’s fasting glucose
indicates that she might have type 2 DM. liraglutide is an option that
will lower her blood glucose as well produce clinically significant
85. BUPROPION/ZONISAMIDE ER
• In a 24 week phase II clinical trial bupropion/zonisamide
ER has shown to produce a weight loss of 9.9% of initial
body weight as compared to 1.7% weight loss with
placebo.
• Bupropion causes appetite suppression by stimulating
proopiomelanocortin neurons in the hypothalamus.
• Zonisamide acts synergistically by suppressing an
appetite stimulating neural pathway.
• The most common adverse effects are headache,
nausea, insomnia.
86. CETILISTAT
• It is a lipase enzyme inhibitor, i.e., acts by inhibiting
gastric and pancreatic lipase and thereby reducing the
dietary fat absorption.
• It acts similarly to orlistat, with a more tolerable side
effect profile.
• In a 12 week phase II clinical trial, cetilistat produced
a mean weight loss of 4.32 kg when taken at a dose of
120 mg 3 times a day by obese patients with diabetes.
• The most common adverse effects were mild-to-
moderate GI effects.
87. TESOFENSINE
• Tesofensine, an inhibitor of noradrenaline, dopamine,
and serotonin reuptake, was initially developed to
treat neurodegenerative diseases, and was found to
produce a weight loss in obese patients with
Parkinson’s or Alzheimer’s disease.
• The agent when used in combination with caloric
restriction has shown to produce a dose-dependent
weight reduction of up to 10.6% of baseline body
weight after 24 weeks of therapy.
• Adverse effects associated with tesofensine are
nausea, constipation, diarrhea, dry mouth and
88. TAUROURSODEOXYCHOLIC ACID
• It has been shown to produce a weight loss by increasing
the sensitivity to leptin, a hormone that acts to suppress
appetite.
• However, no clinical data is currently available.
