New approvals and pipeline drugs for obesity

1. RECENT ADVANCES
IN
OBESITY
Shreya Gupta

2. INTRODUCTION
• Word obesity is derived from the Latin word “obesus” meaning
“having eaten until fat”
• For adults, WHO defines Overweight : BMI ≥ 25 kg/m2
Obese : BMI ≥ 30 kg/m2
• Revised guidelines for India, Overweight : BMI ≥ 23 kg/m2
Obese : BMI ≥ 25 kg/m2
• Worldwide prevalence (WHO): In 2016, > 1.9 billion adults
were overweight, of these
650 million were obese.
• Indian prevalence (ICMR) : In 2015, >135 million adults were
obese.

3. 2013 AHA/ACC/TOS Guidelines for the
Management of Overweight and Obesity in
Adults.
Disease Riska (Relative to Normal
Weight and Waist
Circumference)
Classification of Overweight and
Obesity by Body Mass Index, Waist
Circumference, and
Associated Disease Risk
Men
≤40 in (≤102 cm) >40 in (>102 cm)
Women
BMI (kg/m2) Obesity Class ≤35 in (≤89 cm) >35 in (>89 cm)
Underweight < 18.5 - - -
Normal weightb 18.5- 24.9 - - Increased
Overweight 25- 29.9
30- 34.9 I
Increased
High
High
Very high
Obese 35- 39.9 II Very high Very high
Extremely obese ≥ 40 III Extremely high Extremely high
a Disease risk for type 2 diabetes, hypertension, and cardiovascular disease.
b Increased waist circumference can also be a marker for increased risk even in persons of
normal weight.

4. ETIOPATHOGENESIS
• Obesity occurs when there is increased energy storage
resulting from an imbalance between energy intake and
energy expenditure over time.
• The specific etiology for this imbalance is multifactorial, with
genetic and environmental factors contributing to various
degrees.
• In a small minority of individuals, excess weight may be
attributed to an underlying medical condition or an
unintended effect of a medication.

5. Genetic factors
1. Syndromic: Prader-Willi, Wilms’ tumor,
Simpson-Golabi-Behmel, Cohen, Bardet-
Biedl, Carpenter, and Wilson-Turner
syndromes
2. Non syndromic: LEP, LEPR, POMC, NPY,
MC4R, UCP1-3 genes
Environmental factors
1. Sedentary lifestyle
2. High-fat foods
3. Cultural factors
4. Socioeconomic status
5. Religious beliefs
Medical conditions
1. Cushing syndrome
2. Growth hormone deficiency
3. Insulinoma
4. Leptin deficiency
5. Psychiatric disorders
Medications
1. Anti convulsants: carbamazepine,
gabapentin, valproic acid
2. Antidepressants: mirtazapine, TCAs
3. Antipsychotics : clozapine, haloperidol.
olanzapine, quetiapine, risperidone
4. Hormones: steroids, insulin,
medroxyprogesterone
OBESITY

6. Anatomic location Increased eating Decreased eating
Arcuate nucleus of
hypothalamus
NPY
AgRP
α MSH Insulin
GLP-1 CART
PYY Leptin
Paraventricular
nucleus of
hypothalamus
NPY
AgRP
α MSH
CRH
CCK
Lateral
hypothalamus
Orexin
MCH
Hypothalamus NE α2
5 HT 1A
NE α1 and β2
5 HT1B , 5HT2c
Histamine H1 and H3
Nucleus accumbens Dopamine
Brainstem
(hindbrain)
NPY
AgRP
Opioids
Leptin
α MSH
CCK
Vagus nerve Ghrelin Leptin GLP-1
CCK PYY
Effects of Various Neurotransmitters, Receptors, and Peptides on Food
Intake

7. Overweight/ obese
BMI ≥ 25kg/m2
Patient motivated to maintain
or lose weight
Secondary obesity
Secondary obesity (eg.
Hypothyroidism, Cushing
syndrome, hypothalmic causes
Counsel regarding risks of
overweight and obesity
Medical workup of cause, initiate
treatment
Assess degree of obesity
and concurrent risk
factors: HTN,
dyslipidaemia, CHD, type
2 DM, sleep apnoea,
increased WC
BMI ≥25 <27
BMI ≥27 <30
BMI ≥30 <35
BMI ≥35 <40
BMI ≥ 40
Drug therapy
Lifestyle
therapy
Weight
maintenance
Surgery
With or without risk factors
≥2 risk factors
≥1 risk factor
≤ 1 risk factor
≤ 1 risk factor
≥2 risk factors
No risk factor
No
Yes
No
TREATMENT ALGORITHM FOR OBESITY
Yes

8. PAST ANTI- OBESITY DRUGS
DRUG APPROVED MECHANISM REASON FOR
WITHDRAWAL
Amphetamine 1947 Central NE release Abuse potential
Aminorex 1965 Central NE release Pulmonary HTN
Fenfluramine 1973 Serotonin agonist Heart valvulopathy
Phenylpropanolamine 1976 α adrenergic agonist Haemorrhagic stroke
Caffeine and ephedra 1994 Non selective
adrenergic agonist
Cardiac, psychiatric SEs
Sibutramine 1997 NE/serotonin reuptake
inhibitor
MI, stroke, death
Rimonabant 2005 Cannabinoid 1
antagonist
Depression and suicide

9. KEY CONCEPTS
• BMI and waist circumference(WC), measured regardless of sex
are independent predictors of obesity-related disease risk.
• Weight loss of even 5% of total body weight can significantly
improve blood pressure, lipid levels and glucose tolerance in
overweight and obese patients.
• High probability of weight gain after discontinuation of therapy.
• Pharmacotherapy should be discontinued if weight loss of at
least 5% is not achieved after 12 weeks of maximum dose
therapy with lorcaserin, phentermine-topiramate or bupropion-
naltrexone.
• Discontinue liraglutide if atleast 4% weight reduction is not
achieved after 16 weeks of therapy

10. CURRENT NON-PHARMACOLOGICAL THERAPY
FOR OBESITY
Source: Jensen MD, Ryan DH, Apovian CM, Ard JD, Comuzzie AG, Donato KA, et al. 2013 AHA/ACC/TOS Guideline for
the Management of Overweight and Obesity in Adults. Circulation. 2013;129.

11. CURRENT PHARMACOLOGICAL THERAPY
FOR OBESITY
Drug Mechanism of
action
Contraindications Side effects
Phentermine Appetite- suppressant
drug
Causes NE release+
minor DA release
Cardiovascular disease,
hyperthyroidism,
glaucoma, agitated
states, pregnancy
Insomnia, dry mouth,
constipation, agitation,
HTN
Orlistat Modulates dietary
absorption of fats by
reducing fat hydrolysis
& absorption by
inhibiting gastric &
pancreatic lipases
Chronic malabsorption
syndrome, cholestasis,
pregnancy
Oily spotting, flatus with
discharge, diarrhoea,
faecal urgency
Phentermine/
Topiramate
Topiramate:
neurostabilizer,
enhance
thermogenesis
Phentermine: appetite
suppressant
Glaucoma,
hyperthyroidism
pregnancy
Parasthesia, dizziness,
dysguesia, insomnia,
constipation, dry mouth

12. Drug Mechanism of action Contraindications Side effects
Lorcaserin Selective 5-HT2c
receptor agonist
Causes elevation of
satiety, reduction in
craving and impulsivity
Pregnancy Non diabetics: headache,
dizziness, fatigue, nausea,
dry mouth
Diabetics: hypoglycemia,
headache, back pain,
cough, fatigue
Naltrexone/
Bupropion SR
Bupropion: stimulates
POMC
Naltrexone: blocks
orexigenic effects of β
endorphin activity
Uncontrolled HTN,
seizures, chronic
opioid use,
pregnancy
Nausea, constipation,
headache, insomnia, dry
mouth, diarrhoea
Liraglutide GLP-1 receptor agonist
Directly stimulates
POMC and other
anorexigenic neurons
Activates reward
system: ventral
trigeminal area, nucleus
accumbens
Personal/family
history of medullary
thyroid Ca, MEN
type 2, pregnancy
Nausea, hypoglycemia,
diarrhoea, constipation,
decreased appetite,
dyspepsia, abdominal pain

13. NEED FOR NEW DRUGS
• There is a surprisingly huge void in the current
pharmacological treatment options for obesity, despite the
high prevalence and associated costs of obesity.
• Many factors have prevented active drug development,
including the poor safety and efficacy of earlier anti-obesity
drugs.
• Obesity needs to be managed like a chronic disease, with
combination therapies and long-term treatment in order to
achieve sustained success.
• New targets will require an understanding of the complex
circuitry that controls energy homeostasis

14. CENTRALLY ACTING ANTI OBESITY
TARGETS
Recent Advances

15. TESOFENSINE
• Group: Serotonin-norepinephrine-dopamine-reuptake inhibitor
(SNDRI)
• Mechanism of action: Presynaptic reuptake inhibitor of
dopamine, norepinephrine and serotonin
• Half life: 8 days
• Current status: Undergoing PHASE III trial, to study change in
body weight in 372 adults with obesity treated
with placebo, 0.25 or 0.5 mg tesofensine
for 24 weeks, expected to complete in 2018.

16. SETMELANOTIDE
• Group: Melanocortin-4 receptor (MC4R) agonist
• Mechanism of action:
1. Appetite suppressant effects by binding to and activating MC4
receptors in the paraventricular nucleus (PVN) of
the hypothalamus and in the lateral hypothalamic area (LHA),
areas involved in the regulation of appetite.
2. Increases resting energy expenditure in both obese animals and
humans
• Orphan drug status for Prader-Willi-Syndrome
• Route of administration: Once daily subcutaneous injection

17. SETMELANOTIDE
• Current status: Undergoing Phase II trial: Setmelanotide
(RM493) Phase II Treatment Trial in Patients
With Rare Genetic Disorders of Obesity.
(including POMC deficiency, LepR deficiency, Bardet-Biedl
syndrome and Alström syndrome)
• Simultaneously undergoing: Long Term Extension Trial of
Setmelanotide (RM-493) for
Patients Who Have Completed a
Trial of Setmelanotide for the
Treatment of Obesity Associated
With Genetic Defects Upstream of
the MC4 Receptor in the Leptin-
melanocortin Pathway

18. SEMAGLUTIDE
• Group: GLP -1 receptor agonist
• Weekly subcutaneously injectable formulation received
FDA approval in 2017, as adjunct to diet and exercise to
improve glycemic control in adults with type 2 diabetes
mellitus.
• Current status: Undergoing PHASE III trial: Efficacy and
Safety of Oral Semaglutide Versus Placebo
in Subjects With Type 2 Diabetes Mellitus
Treated With Diet and Exercise Only
(PIONEER 1)

19. VELNEPERIT
• Group: Neuropeptide Y Antagonist
• Mechanism of action: Prevents binding of NPY to Y5 receptors,
thus decreasing hunger and increasing
satiety
• Current status: Discontinued, after results showed no
significant benefit over placebo in Phase II trials
• Currently being evaluated in combination with Orlistat:
Double-Blind, Multi-Center, Randomized, Parallel-Group Study to
Assess the Efficacy and Safety of 400 mg of Velneperit (S-2367)
and 120 mg of Orlistat Administered Individually or Combined
Orally Three Times Per Day With a Reduced Calorie Diet (RCD) in
Obese Subjects

20. CANNABINOID TYPE 1 RECEPTOR
BLOCKER
• Activation of cannabinoid type-1 (CB1) receptors by
cannabinoid stimulates orexigenic signaling while antagonism
of CB1 receptors stimulates anorexigenic signaling leading to
inhibition of food intake.
• Older CB1 blocker, Rimonabant has been withdrawn due to
mood fluctuations and suicidal ideation
• Pre-clinical trial : Novel compound AM6545, with limited CNS
penetration is being evaluated in mice, in whom it inhibited
food intake and weight gain without any aversive side effects.

21. ZONISAMIDE-BUPROPION
• Zonisamide : Antiepileptic agent with properties of sodium
channel modulation, carbonic anhydrase inhibition, and
enhancement of dopamine and serotonin transmission, used to
treat partial seizures with weight loss as a side effect.
• Bupropion: Dopaminergic agent, approved for the treatment of
depression and smoking cessation, also decreases appetite and
weight loss as monotherapy.
Rationale for combination:
1. All 3 major neurotransmitters that regulate appetite and energy
homeostasis being targeted
2. Zonisamide-induced sedation, psychomotor slowing, cognitive
dysfunction, fatigue and depression coupled with its anti-seizure
properties complement well to the insomnia, psychomotor
agitation and anti-depressive effects of bupropion

22. • Current status: Completed Phase II trial
• Results:
 Out of 729 patients enrolled, those in the treatment arm had
greater weight loss (bupropion 360 mg + 120 mg zonisamide
dosage −6.1%; bupropion 360 mg + 360 mg zonisamide − 7.5%)
compared to placebo (1.4%) in 24 week phase trial
 Monotherapy with zonisamide weight loss was 3.2% with 120
mg and 5.3% with 360 mg and with bupropion 2.3 % with 360
mg
 In the buproprion 360 mg + 120 mg zonisamide group, 46.9%
of patients lost > 5% of initial bodyweight and 60.4% in the
buproprion 360 mg + zonisamide 360 mg group

23. PERIPHERAL ANTI OBESITY TARGETS
Recent Advances

24. CETILISTAT
• Group: Pancreatic Lipase inhibitor
• Mechanism of action: Inhibition of pancreatic lipase reduces
this conversion and the absorption of free fatty acids in the
intestine, resulting in increased excretion of triglycerides in
the urine.
• Current status: undergoing Phase III trials in USA and Europe
• In Phase II trial it was as effective as orlistat with superior
safety profile and less GI side effects.

25. RESVERATROL
• Group: SIRT1 activator
• SIRT1 (silent information regulator 1 proteins) or Sirtuins,
participate in lipid metabolism and insulin resistance. SIRT1
suppresses expression of PPARγ that is responsible for fat storage.
• Mechanism of action: Resveratrol is allosteric activator of
SIRT1, also increases the mitochondrial
activity in brown adipose tissue and
skeletal muscle.
• Current status: Undergoing Phase III trial: Effect of Resveratrol
on Insulin Resistance and Inflammatory
Mediators in Obese and Type 2 Diabetic Subjects

26. AMYLIN MIMETICS
• Amylin, a pancreatic B-cell hormone, acts as a centrally acting
satiety signal, reducing food intake, slowing gastric emptying,
and reducing postprandial glucagon secretion by exerting an
effect through the area postrema.
• Amylin signal exerts a control over energy pathways by
decreasing the expression of orexigenic neuropeptides
a) Davalintide (AC2307) : Amylin mimetic, was evaluated for
obesity and psychiatric disorders.
Current status : Discontinued for both uses in 2012.
b) NN9838: Currently undergoing Phase 1 trial

27. DUAL AMYLIN AND CALCITONIN
AGONISTS (DACRA)
• Human amylin receptor subtypes are complexes of the
calcitonin receptor with receptor activity-modifying proteins.
• Because of their mechanism of action, amylin mimetics
coupled with calcitonin receptor agonists known as dual
action amylin and calcitonin receptor agonists (DACRA) are
novel anti-obesity drug discovery targets.
• DACRA KBP 088 and KBP 042 are currently undergoing
Pre- clinical trials.
• Both have showed improved glucose tolerance and alleviated
hyperinsulinemia with sustained weight loss effects and
reduction in adipocyte hypertrophy in high-fat diet fed rats.

28. DUAL ACTION GLP-1/GLUCAGON
RECEPTOR CO-AGONISTS
• Glucagon was first noted to reduce food intake in humans over
50 years ago, likely related to its effects on decreasing meal size
and increasing satiety.
• Co-administration of GLP-1 agonist and glucagon noted an
anorectic effect with neuronal activation in the area postrema
and central nucleus of the amygdala in contrast to the
hyperglycemic effect of glucagon monotherapy.
• Oxyntomodulin: Natural GLP-1/Glucagon dual receptor agonist,
produced by enteral L-cells; known to suppress appetite,
decrease food intake and increase energy expenditure.
• The clinical utility of OXM is limited, mainly because of its short
circulating half-life.

29. SYNTHETIC NOVEL DUAL ACTION ANALOGUES
• MEDI0382
Completed Phase II trial : Phase 1/2, Randomized, Double-blind,
Placebo-controlled, Multiple-
ascending-dose Study to Evaluate the
Efficacy, Safety, and Pharmacokinetics
of MEDI0382 in Overweight and Obese
Subjects With a History of Type 2
Diabetes Mellitus.
Primary end points:
1) Change from baseline to day 41 in glucose area under the curve
at 0–4 h after a mixed-meal tolerance test (MMTT), assessed in
all participants who received at least one dose of study drug.
2) Change from baseline in body weight in kg to end of treatment

30. Results:
 Glucose AUC 0–4 h post MMTT decreased significantly with
MEDI0382 versus placebo.
 Reduction in bodyweight was significantly greater with
MEDI0382 than with placebo (p=0·0008).
 No serious adverse events with MEDI0382
Other molecules undergoing Phase 1 trials:
a) G530S (glucagon analogue+ semaglutide)
b) GG Co agonist 1177

31. TRIPLE GLUCAGON-GIP-GLP-1 AGONIST
• Aim for development of single molecules which promote their
biological action through simultaneous agonism at multiple
key metabolic receptors.
• Underlying principle:
 The anorectic action of central GLP-1 receptor agonism
synergizes with the action of glucagon to increase energy
expenditure, resulting in a net loss of body weight.
 The combined glycemic action of GLP-1R and GIP receptor
(GIPR) agonism restrains the hyperglycemic effect of glucagon,
improves insulin sensitivity, and results in body weight
improvements.
• Tri agonist 1706: currently in Phase 1 trial

32. PEPTIDE YY (PYY)
• PYY is a 36-amino-acid anorexigenic peptide secreted from the
enteroendocrine L cells of the ileum and colon in response to
feeding
• Reduces appetite and decrease food intake by decreasing gastric
motility, increasing satiety, and inhibiting NPY receptors.
• Obese patients have lower PYY levels and its rise in PYY is
blunted post-prandially.
• Failure to sustain elevated PYY levels has also been implicated in
weight regain post-bariatric surgery.
• NNC0165-1562
• GT-001 Undergoing Phase 1 trial

33. LEPTIN ANALOGUES
Metreleptin
• Injectable human recombinant leptin analogue
• Mechanism of action: Improves hyperglycemia and
hypertriglyceridemia and decreases
hepatic fatty steatosis, has demonstrated
a role in congenital or acquired
lipodystrophic disorders
• Current status: Approved in Japan for metabolic disorders
including lipodystrophy and in the USA in 2014 as
the first and only treatment of patients with non-
HIV-related forms of generalized lipodystrophy
such as leptin deficiency and congenital or
acquired lipodystrophy

34. LIMITATIONS:
• Development of anti-metreleptin antibody might occur and
has been implicated in possible weight regain or loss of
efficacy associated with metreleptin treatment.
• The drug is thus contraindicated in patients with general
obesity not associated with congenital leptin deficiency due
to lack of efficacy and immunogenicity with neutralizing
activity reported in these patients.

35. PAZ 320
• Group: Carbohydrate hydrolysing inhibitor
• Mechanism of action: Blocks the enzymatic breakdown of
complex carbohydrates into simple sugars, resulting in the
reduction in the intestinal absorption of glucose, fructose
and other monosaccharides.
• Current status: Undergoing Phase III trial for
type 2 diabetes and obesity.

36. ALSL1023
• Group: Matrix metalloproteinase inhibitor
• Mechanism of action: MMPs are endoproteinases that
participate in tissue remodelling and
angiogenesis. Similar to neoplastic
tissues, growth and development of
adipose tissue are thought to be
angiogenesis-dependent. High levels of
MMP are associated with obesity.
• Current status: A Randomized, Double-Blind, Placebo
Controlled, Multicenter, 12-week Phase III Study to Evaluate
Efficacy and Safety of ALS-L1023 Tablet in Patients With
Abdominal Obesity of Metabolic Syndrome
• No results posted yet.

37. NOVEL APPROACHES FOR OBESITY
Recent Advances

38. BELORANIB
• Group: Methionine aminopeptidase 2 (MetAP2) inhibitor
• Analogue of the natural chemical compound fumagillin
• Mechanism of action: Inhibits angiogenesis, converts stored
fats into useful energy and reduce the
production of new fatty acid
molecules.
• The development of this drug was terminated during phase
2 due to increased incidence of thromboembolic events.

39. • The gut-brain axis is a complex neurohumoral communication
network imperative for maintaining metabolic homeostasis.
• It is comprised of the CNS, enteric nervous system (ENS), the
autonomic nervous system (ANS) and its associated
sympathetic and parasympathetic branches, neuroendocrine
and immunological systems, including the gut microbiota.
• Role of gut microbiota is being increasingly implicated in obese
individuals, with respect to dietary changes, microbiota
composition and energy harvesting mechanisms.
GUT- BRAIN AXIS: ROLE OF MICROBIOTA

40. INFLUENCES OF MICROBIOTA IN
OBESITY

41. ROLE OF BACTERIOTHERAPY
PREBIOTICS
• Prebiotics, such as oligofructose,
increase numbers of Akkermansia,
Faecalibacterium , Bifidobacterium,
and Lactobacilli
• Improve gut-barrier function through
GLP2 mediated pathway and increase
in endocannabinoid signalling
• Induce weight-loss and reduce food
intake, by improving gut nutrient-
sensing mechanisms
• Associated with improved EEC
differentiation and concentrations of
GLP1, GIP and PYY, which increase
satiety, decrease food consumption
and adiposity
PROBIOTICS
• Probiotics, such as Bifidobacterium
and Lactobacillus
• Increase vagal activity
• Decrease LPS and TLR 4 induced
inflammation
• Improve gut barrier function
• Decrease gut permeability
• Increase in both satiety and body
self-esteem scores
• Decrease in both food cravings and
depression

42. ROLE OF OXYTOCIN IN OBESITY
• Has potential anoxerigenic and antiobesity effects.
• In animals: Central and peripheral administration of oxytocin
reduces appetite and, in a longer-term, body weight,
by increasing energy expenditure.
• In humans: Blood oxytocin levels significantly lower in
obese versus normal-weight individuals, and several
obesity-related parameters (BMI,WC, WHR,
cholesterol, and HOMA IR) negatively
correlate with oxytocin plasma concentrations
• In women, obesity also underlies the need to administer higher
doses of IV OT to induce labor

43. • Intranasal oxytocin in humans reduces energy-driven and
reward-driven consumption. It has also shown lowering of insulin
resistance and fasting insulin levels.
• Clinical studies on the Prader–Willi syndrome (PWS) have shown
loss-of-function changes in the oxytocin circuit, including a
decrease in the number and size of hypothalamic oxytocin
neurons and dysregulation of oxytocin release which contribute
to key symptoms of abnormal social behavior, excessive food
intake, and food cravings.
• The intranasal oxytocin regimen has been found to improve both
social and food-related behaviors in PWS children
ROLE OF OXYTOCIN IN OBESITY

44. ROLE OF METFORMIN IN OBESITY
• Metformin is not a weight reducing agent on its own; many
researchers have concluded that metformin might halt the
weight gain in diabetics or from medications like insulin,
thiazolidinedione, sulfonylureas, antipsychotics, etc.
• The weight changes are more prominent in patients with
impaired glucose tolerance, unlike in non- diabetic obese
people in whom mixed results have been seen with metformin.
• Mechanistic explanation of metformin and weight loss has been
attributed to:
1. Modest reduction in the carbohydrates uptake in the gut
2. Modulation of the vicious cycle of the insulin resistance,
3. Reduction in leptin levels,
4. Augmentation of the GLP-1 effects on fat cells

45. BROWN ADIPOSE TISSUE
• Brown adipose tissue (BAT) oxidizes chemical energy to produce
heat energy. This heat energy can act as a defense against
hypothermia and obesity.
• Overall thermogenic capacity is about 100-300 kcal/day.
• Brown fat selective genes like UCP-1, CIDEA and PPARGC1A are
involved in thermogenesis.
• Potential targets for BAT activation:
1. Several peptides including thyroid hormone (T3)
2. PRDM16 protein, present in white adipose tissue, leads to the
production of brown fat-like adipocytes within white adipose
tissue, called beige cells (also called brite cells). These beige
cells have a brown adipose tissue-like phenotype and actions,
including thermogenic processes seen in BAT.

46. ACTIVATION OF
BROWN ADIPOSE
TISSUE
OREXIN A
IRISIN
METORIN
FGF21
NATRIURETIC
PEPTIDES
PRDM16
protein
Triiodothyro
nine

47. VACCINES FOR OBESITY
Recent Advances

48. Vaccine Vaccine principle Type of vaccine Vaccination results Species
Adipose
tissue
antigens
To decrease
inflammatory
response by
inducing immune
tolerance toward
self-antigens
Oral
immunization
against adipose
tissue antigens
Reduces waist
circumference.
Decreases
triglycerides and
increases HDL-
cholesterol.
Negligible effect on
body weight.
Human
Somatostatin To prevent inhibitory
effects of
somatostatin, in
order to increase the
endogenous levels
of GH and IGF-1
Chimeric-
somatostatin
No change in food
intake.
10% decrease body
weight gain under
high fat diet.
Mice

49. Vaccine Vaccine principle Type of vaccine Vaccination results Species
Glucose-
dependent
insulinotropic
polypeptide
(GIP)
GIP blockade to
increase fat
oxidation and
improve insulin
resistance.
Immunoconjugate
of GIP covalently
attached to the Qβ
bacteriophage.
Protects against diet
induced obesity.
Decreases fat
accumulation.
Increases resting
energy expenditure.
No changes in
locomotor activity.
Mice
Glucose-
dependent
insulinotropic
polypeptide
(GIP)
GIP blockade to
increase fat
oxidation and
improve insulin
resistance.
Immunoconjugate
of GIP covalently
attached to the Qβ
bacteriophage
Protects against diet
induced obesity.
Decreases fat
accumulation.
Increases resting
energy expenditure.
No changes in
locomotor activity.
Mice
Ghrelin To suppress
endogenous
ghrelin
bioactivity
Ghrelin conjugated
to BSA (plus
adjuvants).
Decreases food
intake by 15%
Decreases body
weight by 10%
Pigs

50. MEDICAL DEVICES FOR OBESITY
Recent Advances

51. MEDICAL DEVICES FOR OBESITY
FDA-regulated medical devices also help treat obesity.
Currently, there are four types of FDA-approved devices
marketed to treat obesity:
• Gastric Band Technique
• Electrical Stimulation Systems
• Gastric Balloon Systems
• Gastric Emptying Systems

52. Lap-Band Adjustable Gastric Banding
System
• Gastric Band - bands are
placed around the top
portion of the stomach
leaving only a small portion
available for food.
• Indicated in obese adults with
BMI ≥40 or BMI ≥35 with one
or more severe comorbidities,
who have been obese for at
least five years and for whom
non-surgical weight loss
methods have not been
successful.

53. Maestro Rechargeable System
• Electrical Stimulation System
- electrical stimulator is
placed in the abdomen to
block transmission of signals
in the vagus nerve (vagal
blocking therapy, or VBLOC
therapy).
• Suppresses neural
communication between the
brain and the stomach
• Indicated in obese adults,
with BMI 40 to 45 or with a
BMI of 35 to 39.9 and one or
more obesity-related health
conditions

54. Gastric Balloon Systems
1) ReShape Integrated
Dual Balloon
BMI of 30 – 40 kg/m2 + ≥ 1
comorbidities
Inflatable balloons are placed in the stomach to take up space.
2) ORBERA Intragastric
Balloon System
BMI of 30 – 40 kg/m2

55. 3) The Obalon Balloon System (the ‘System’)
• This is a swallowable intragastric balloon system delivered via capsule.
• Consists of up to 3 intragastric balloons placed during a 6-month period
• Fully inflated single balloon is an ellipsoid with a volume of
approximately 250cc.
• Indicated in obese adults with BMI of 30 – 40 kg/m2 who have failed to
lose weight through diet and exercise.
• The System is to be used as an adjunct to a moderate intensity diet
and behavior modification program.

56. AspireAssist
• Gastric Emptying System - a tube
is inserted between the stomach
and outside of abdomen to drain
food after eating.
• Indicated in patients aged ≥22 ,
with BMI 35 to 55 kg/m2, and have
failed to achieve and maintain
weight loss through
pharmacotherapy.
• Once opened, it takes 5-10
minutes to drain food matter
through the tube into the toilet.
• Removes approx. 30% of the
calories consumed.

57. PREVAILING CONTROVERSIES..
• None of the current FDA approved drugs for obesity have
shown cardiovascular benefit.
• The optimal treatment duration of these drugs remains
unknown.
• As discontinuation of a drug treatment tends to cause weight
regain, continuation of an effective and well tolerated drug
regimen is common practice.
• Personalized pharmacotherapy is the need of the hour, but
recommendations regarding how the current medications can
be individualized to maximize patient benefit are not yet
available.

58. THANK YOU!

59. REFERENCES
• Overweight and obesity [Internet]. World Health Organization. World Health
Organization; 2017 [cited 2018Oct8]. Available from:
http://www.who.int/gho/ncd/risk_factors/overweight_text/en/
• Mohan V, Pradeepa R, Anjana R, Joshi S, Bhansali A, Deepa M, et al. Prevalence of
generalized & abdominal obesity in urban & rural India- the ICMR - INDIAB Study
(Phase-I) [ICMR - INDIAB-3]. Indian Journal of Medical Research. 2015;142(2):139.
• Appropriate body-mass index for Asian populations and its implications for policy and
intervention strategies. The Lancet. 2004;363(9403):157–63.
• Sheehan A, Chen J, Yanovski J, Calis K. Obesity. In: DiPiro J, Talbert R, Yee G.
Pharmacotherapy: A Pathopysiologic Approach. 10th ed. New York: McGraw-Hill;2017.
p.2385-2402
• Srivastava G, Apovian C. Future Pharmacotherapy for Obesity: New Anti-obesity Drugs
on the Horizon [Internet]. SpringerLink. Humana Press; 2018 [cited 2018Oct8].
Available from: https://link.springer.com/article/10.1007/s13679-018-0300-4
• Coulter AA, Rebello CJ, Greenway FL. Centrally Acting Agents for Obesity: Past, Present,
and Future [Internet]. SpringerLink. Humana Press; 2018 [cited 2018Oct8]. Available
from: https://link.springer.com/article/10.1007/s40265-018-0946-y
• Jakab J, Smolić R, Včev A, Smolić M. Drug Treatment of Obesity: From Bench to
Bedside. Drug Discovery - Concepts to Market. 2018

60. • Fasipe O. Recent advances and current trend in the pharmacotherapy of obesity.
Archives of Medicine and Health Sciences. 2018;6(1):99.
• Efficacy and Safety of Oral Semaglutide Versus Placebo in Subjects With Type 2
Diabetes Mellitus Treated With Diet and Exercise Only - Full Text View [Internet].
Search of: Spain - List Results - ClinicalTrials.gov. [cited 2018Oct2]. Available from:
https://clinicaltrials.gov/ct2/show/NCT02906930
• Jall S, Sachs S, Clemmensen C, et al. Monomeric GLP-1/GIP/glucagon triagonism
corrects obesity, hepatosteatosis, and dyslipidemia in female mice. Molecular
Metabolism. 2017;6(5):440-446. doi:10.1016/j.molmet.2017.02.002.
• Center for Devices and Radiological Health. Obesity Treatment Devices [Internet].
U S Food and Drug Administration Home Page. Center for Drug Evaluation and
Research; [cited 2018Oct6]. Available from:
https://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/ObesityDev
ices/default.htm
• Bliss ES, Whiteside E. The Gut-Brain Axis, the Human Gut Microbiota and Their
Integration in the Development of Obesity. Frontiers in Physiology. 2018Dec;9.
• Desilets AR, Dhakal-Karki S, Dunican KC. Role of Metformin for Weight
Management in Patients Without Type 2 Diabetes. Annals of Pharmacotherapy.
2008;42(6):817–26.
• Park BY, Lee H, Woo S, Yoon M, Kim J, Hong Y, et al. Reduction of Adipose Tissue
Mass by the Angiogenesis Inhibitor ALS-L1023 from Melissa officinalis. Plos One.
2015;10(11).