This document summarizes recent advances in obesity, including potential new drug targets. It discusses drugs currently in development like tesofensine, setmelanotide, semaglutide, and velneperitide that act on targets such as serotonin-norepinephrine-dopamine reuptake, melanocortin receptors, GLP-1 receptors, and neuropeptide Y receptors. The document also mentions exploring cannabinoid type 1 receptor blockers with limited brain penetration to avoid the psychiatric side effects that led to previous drugs being withdrawn.
Anti-Obesity Pharmacotherapy: Where are we now? Where are we going?InsideScientific
Obesity is a treatable chronic disease. With nearly 2 billion individuals worldwide classified as being overweight and 650 million as having obesity, it is critical to optimize implementation of existing treatment interventions and develop novel therapies to mitigate the obesity pandemic. Anti-obesity medications are one of the essential tools in our medical toolbox to help patients achieve their health and weight goals.
In this webinar, Dr. Jastreboff discusses current use of anti-obesity pharmacotherapy, mechanisms involved, and agents in various stages of development with considerations for next steps. The presentation aims to inspire development of innovative therapeutics while optimizing use of existing agents to address the urgent need to effectively and sustainably treat millions of individuals with obesity around the world.
Key Topics Include:
- Understand the role of anti-obesity pharmacotherapy in the treatment of obesity
- Describe current anti-obesity pharmacotherapy
- Discuss anti-obesity medications under development
GLP-1 is an incretin (hormone that increases insulin secretion in response to a meal), which is a 30-amino acid peptide secreted in response to the oral ingestion of nutrients by intestinal L cells.
GLP-1 receptors (GLP-1R) are located in islet cells, central nervous system, and other organs. GLP-1 is metabolized by the enzyme dipeptidyl peptidase-4 (DPP-4).
Incretin effect is a phenomenon whereby a glucose load delivered orally produces a much greater insulin secretion than the same glucose load administered intravenously.
This presentation is an overview of the entire GLP-1 system, followed by an introduction to leveraging its therapeutic potential using GLP-1 analogues (Exenatide, Liraglutide, Lixisenatide, Albiglutide, Dulaglutide) and DPP-4 inhibitors (Sitagliptin, Vildagliptin, Saxagliptin, Linagliptin, Anagliptin, Teneligliptin, Alogliptin, Trelagliptin, Omarigliptin).
Shashikiran Umakanth delivered this talk at Manipal on 30th November, 2015
Anti-Obesity Pharmacotherapy: Where are we now? Where are we going?InsideScientific
Obesity is a treatable chronic disease. With nearly 2 billion individuals worldwide classified as being overweight and 650 million as having obesity, it is critical to optimize implementation of existing treatment interventions and develop novel therapies to mitigate the obesity pandemic. Anti-obesity medications are one of the essential tools in our medical toolbox to help patients achieve their health and weight goals.
In this webinar, Dr. Jastreboff discusses current use of anti-obesity pharmacotherapy, mechanisms involved, and agents in various stages of development with considerations for next steps. The presentation aims to inspire development of innovative therapeutics while optimizing use of existing agents to address the urgent need to effectively and sustainably treat millions of individuals with obesity around the world.
Key Topics Include:
- Understand the role of anti-obesity pharmacotherapy in the treatment of obesity
- Describe current anti-obesity pharmacotherapy
- Discuss anti-obesity medications under development
GLP-1 is an incretin (hormone that increases insulin secretion in response to a meal), which is a 30-amino acid peptide secreted in response to the oral ingestion of nutrients by intestinal L cells.
GLP-1 receptors (GLP-1R) are located in islet cells, central nervous system, and other organs. GLP-1 is metabolized by the enzyme dipeptidyl peptidase-4 (DPP-4).
Incretin effect is a phenomenon whereby a glucose load delivered orally produces a much greater insulin secretion than the same glucose load administered intravenously.
This presentation is an overview of the entire GLP-1 system, followed by an introduction to leveraging its therapeutic potential using GLP-1 analogues (Exenatide, Liraglutide, Lixisenatide, Albiglutide, Dulaglutide) and DPP-4 inhibitors (Sitagliptin, Vildagliptin, Saxagliptin, Linagliptin, Anagliptin, Teneligliptin, Alogliptin, Trelagliptin, Omarigliptin).
Shashikiran Umakanth delivered this talk at Manipal on 30th November, 2015
SGLT2I The paradigm change in diabetes managementPraveen Nagula
Just like ARNI, SGLT2I have changed the face of diabetes management and they have a good profile in multimodality management because of pleiotropic effects
Diabetes is often accompanied by high triglyceride and high cholesterol levels. Saroglitazar (Lipaglyn) is a novel molecule that not only reduces elevated TG levels; it also reduces blood glucose levels. This presentation by Dr Vivek Baliga discusses this novel molecule.
Tirzepatide is the new class of anti diabetic drug which was recently approved by US FDA.
It is the first drug which belongs to dual channel agonist. It is best medicine from compared to other diabetes drug
SGLT2I The paradigm change in diabetes managementPraveen Nagula
Just like ARNI, SGLT2I have changed the face of diabetes management and they have a good profile in multimodality management because of pleiotropic effects
Diabetes is often accompanied by high triglyceride and high cholesterol levels. Saroglitazar (Lipaglyn) is a novel molecule that not only reduces elevated TG levels; it also reduces blood glucose levels. This presentation by Dr Vivek Baliga discusses this novel molecule.
Tirzepatide is the new class of anti diabetic drug which was recently approved by US FDA.
It is the first drug which belongs to dual channel agonist. It is best medicine from compared to other diabetes drug
DEFINITION AND MEASUREMENT Obesity is a state of excess adipose tissue mass. Although often viewed as equivalent to increased body weight, this need not be the case—lean but very muscular individuals may be overweight by numerical standards without having increased adiposity.
Body mass index (BMI), which is equal to weight/height2 (in kg/m2 )
Body weights are distributed continuously in populations, so that choice of a medically meaningful distinction between lean and obese is somewhat arbitrary. Obesity is therefore defined by assessing its linkage to morbidity or mortality
power point presentation on obesity by Rajeshwaree Netha (Doctor of pharmacy).
contents included are Introduction,pathophyisiology,clinical presentation (signs and symptoms of obesity disorder) ,Treatment,goals of treatment, general approach, Pharmacological treatment, and Evaluation of therapeutic outcomes.
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).
“... good health is more than just exercise and diet. It’s really a point of view
and a mental attitude you have about yourself.”
....Albert Schweitzer
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
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.
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
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
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.
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
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.
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
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.
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.
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• Park BY, Lee H, Woo S, Yoon M, Kim J, Hong Y, et al. Reduction of Adipose Tissue
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Editor's Notes
Abdominal obesity (AO) was defined as a waist circumference (WC) ≥90 cm for men and ≥80 cm for women with or without GO.
WHR 0.88 males, 0.8 females
While the precise definition of
childhood obesity is still lacking, the Endocrine Society clinical practice guideline currently classifies
children and adolescents ages 2 to 18 years with a BMI at the 95th percentile or above as obese, and
those with a BMI between the 85th and 94th percentiles as overweight
Because BMI may
overestimate the degree of excess body fat in some clinical situations (eg, edematous states, extreme
muscularity, muscle wasting, and short stature), the assessment of body composition in such cases
often requires clinical judgment.
BMI is an acceptable measure of obesity and is the practical method of defining obesity in the
clinic and epidemiologic studies; however, it does not always correspond to excess fat. There are
well-established differences in the relationship between BMI and obesity-related risks among
disparate racial, sex, and ethnic groups.
Psychiatric disorders, such as depression, binge eating disorder, and s schizophrenia
This combination is recommended
as first-line therapy for all patients with BMI more than or equal to 25 kg/m2 by The Endocrine
Society Clinical Practice Guidelines for the Pharmacological Management of Obesity (graded as
strong recommendation with high quality evidence).35 Although the difference is subtle, it should be
noted that the AHA/ACC/TOS Guidelines for the Management of Overweight and Obesity in Adults
do not recommend weight loss therapy for patients with BMI between 25 and 29.9, unless the patient
has CVD risk factors.5 Weight loss will require significant effort on the part of the patient to change
their lifestyle and comply with the management plan.
Severely obese individuals will require more
energy, at least at the start of dietary restriction. Adherence to the LCD has been shown to result in
an average weight loss of 8% after 6 months
The challenge is to develop a diet plan that leads to consistent adherence by the patient
and sustained weight loss and maintenance.
it was originally developed to
treat Alzheimer’s and Parkinson’s diseases, efficacy criteria
were not met and the unintended side effect of weight loss
was observed in multiple clinical trials
24-week phase IIb double-blind, placebocontrolled
trial [24] of Empatic in 729 patients with obesity
(BMI 27–45 kg/m2), patients 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%) and monotherapy with zonisamide
(3.2% on 120 mg and 5.3% 360 mg) and bupropion 360 mg
(2.3%). 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
Glucagon is a catabolic hormone involved in raising blood glucose through glycogen breakdown and glucose release by hepatocytes
Patients received once-daily subcutaneous injections of the study drug at doses of no more than 300 μg for 22 days or less in the MAD portion of the study, and a dose of no more than 200 μg for 41 days or less in the phase 2a portion
Leptin, a hormone produced by adipocytes, was initially thought
to be a successful treatment for obesity as early animal studies
linked leptin deficiency to severe obesity. However, on the contrary,
persons with obesity are leptin-resistant and have higher
levels of leptin
Previous indication for hypothalamic amenorrhea
has been discontinued [66].
Similar to neoplastic tissues, growth and development of adipose tissue are thought to be angiogenesis-dependent. Since visceral adipose tissue (VAT) is associated with development and progression of nonalcoholic fatty liver disease (NAFLD), we hypothesized that angiogenesis inhibition would attenuate obesity-induced NAFLD
Expansion of adipose tissue requires continuous remodelling of capillary networks. Since obesity involves the pathological formation of angiogenetic vessels, inhibiting angiogenesis could be a novel treatment target . Vwas primarily used as a therapy for solid tumours.
Approximately 60 g of dietary carbohydrates consumed daily part of the typical western diet are indigestible. The gut microbiota possesses specific glycoside hydrolases, enabling them to ferment and hydrolyse indigestible polysaccharides and produce SCFA as a metabolite within the distal colon (Moran and Shanahan, 2014). This function and subsequent generation of SCFA provides approximately 10% of the host’s daily energy requirements (Schwiertz et al., 2010). Butyrate, propionate and acetate account for 95% of the biologically significant SCFA produced (Bauer et al., 2016). Colonocytes utilise butyrate as their primary energy source, the liver utilises propionate in gluconeogenesis after it has entered the portal circulation and acetate is circulated systemically to various peripheral tissues (Gao et al., 2009; Bauer et al., 2016). Butyrate production is typically attributed to Firmicutes, whilst propionate synthesis is generally associated with Bacteroidetes (Moran and Shanahan, 2014). In the obesogenic state, faeces contain an increased quantity of SCFA, in particular, propionate (Schwiertz et al., 2010). This increase in faecal SCFA content is proposed to be due to a change in microbiota composition, rather than differences in diet and/or SCFA absorption within the colon (Schwiertz et al., 2010; RahatRozenbloom et al., 2014). Interestingly, Rahat-Rozenbloom et al. (2014) reported a higher proportion of Firmicutes than Bacteroidetes in the overweight cohort, which would correlate with an increase in butyrate production rather than propionate production. Hence, further studies are required to determine the differences between obese and lean individuals and why there is an increase in faecal SCFA content. Furthermore, it is interesting that SCFA, which have been demonstrated to possess anti-carcinogen properties, are increased in the obesogenic state, given that a high-fat high-carbohydrate diet is one predisposing factor attributed to the development of colorectal cancer (Bindels et al., 2012; Grima and Dixon, 2013; Irrazábal et al., 2014). Hence, further studies are required to determine the role SCFA play with respect to the development of colorectal cancer in obesity, as it could be argued that possessing a profile mirroring a slightly overweight state, where SCFA production is slightly increased, could be gastroprotective and that increased weight leading to obesity, may be detrimental.
waist-to-hip ratio WHR
Homeostasis model of IR
Normal oxytocin level:
Challenges: a) Developing ligands that can better target central subpopulations of the OTR
b) Dietary strategies for its use
c) Curbing its involvement in processes like parturition, lactation, sexual behavior, social and emotional processing
Ucp- uncoupling protein/ thermogenin
Fibroblast growth factor (FGF) 21, expressed primarily in the liver, but also found in adipose tissue, skeletal muscle, and pancreas,
Functions as a metabolic regulator with beneficial effects of both weight loss and improved glycemic control .
Acts as a tri- autocrine, paracrine, and endocrine factor.
In white adipose tissue, FGF21 stimulates glucose uptake and adiponectin secretion with browning in susceptible white adipose tissue depots. In brown adipose tissue, FGF21 also stimulates both glucose uptake and thermogenesis.
FGF21 resistance has been seen in obesity, with increase in its circulating plasma levels.
Currently being evaluated as a pre- clinical target in mice.
V6 is an oral tablet preparation of specially processed pig adipose tissue (fat cells) and is currently approved as a dietary supplement
Patients consented to receive twice-daily dose of two V-6 pills and be subjected to routine laboratory and physical check-ups at 2, 4, 8, and 12 weeks intervals
The main limitations of passive immunization approaches include development of acquired tolerance and lack of long-term effectiveness, due to the reduced half-lives of the antibodies and need of periodic administration, as well as the possibility of activation of compensatory pathways of ghrelin production in common with the other methods used for ghrelin inactivation.
BSAbovine serum albumin
(BMI) of 30 – 40 kg/m2 and one or more obesity-related comorbid conditions. It is indicated for use in adult patients who have failed weight reduction with diet and exercise alone
The ReShape Integrated Dual Balloon System is a temporary implant designed to facilitate weight loss by occupying space in the stomach and producing a sensation of satiety. The dual balloon is delivered transorally down the esophagus and placed into the stomach using the ReShape Delivery Catheter. Once positioned, the dual balloon is inflated with a sterile saline and methylene blue solution, sealed with mineral oil, and left in the stomach for a treatment period of up to six (6) months. At the conclusion of treatment, the dual balloon is aspirated using the ReShape Removal Catheter and removed endoscopically.
The Obalon Balloon Kit capsule is administered to the patient using a normal pill swallowing method. Endoscopy is not required for placement. Fluoroscopy or digital x-ray is required during the placement procedure to verify placement of the balloon in the stomach prior to inflation of the device. Patient must be in the erect position during the administration procedure.
For administration, a Balloon Kit is used, which includes a balloon and catheter assembly. Each balloon is contained within a USP grade porcine gelatin capsule, which is attached to a catheter. The balloon capsule delivers the balloon in a similar manner that a medicinal capsule delivers pharmaceuticals. The catheter comes pre-attached to the compacted balloon’s radioopaque, resealing valve. The administration (placement) procedure requires no sedation. The catheter/capsule is swallowed by the patient. The catheter is then attached to the EzFill Dispenser that contains an EzFill Can (a can containing nitrogen-sulfur hexafluoride gas mixture) to fill the balloon. After the patient swallows a balloon capsule, radiography must be done prior to inflation to ensure the balloon is in the stomach (visualized by the radio-opaque marker). The preferred radiographic method is fluoroscopy or digital x-ray since both provide real-time image of the balloon using low levels of radiation with immediate imaging feedback. Once there is radiographic confirmation that the balloon (radiopaque marker) is below the gastroesophageal junction, then the balloon is then inflated. A fully inflated single balloon is an ellipsoid with a volume of approximately 250cc. When 3 balloons are placed, the total balloon volume is approximately 750cc.
Approximately 20 to 30 minutes after meal consumption, the patient attaches the device’s external connector and tubing to the port valve, opens the valve and drains the contents.