This document outlines Dr. Sahil Kumar's presentation on anti-obesity drugs. It begins with introducing the global rise of obesity and discusses mechanisms that control energy balance like leptin and the hypothalamus. Historical anti-obesity drugs are reviewed along with contemporary FDA-approved options like orlistat, lorcaserin, phentermine-topiramate, naltrexone-bupropion, and liraglutide. The document also explores future developments in anti-obesity drug research and development.
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
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
Inpatient Plant Based Nutrition: Review of the History and Challenges for Ap...EsserHealth
Plant Based nutrition has been show to be one of the most powerful methods to revers and prevent many of the most common cardiometabolic diseases today. In this talk learn about the long history of plant based nutrition in the inpatient setting and about clinics still functioning today. Also review some of the most common challenges keeping it from application in the inpatient setting in most health care settings.
Comparitive Study of the Efficacy and Tolerance of Prokinetic Drugs - Metaclo...pharmaindexing
Comparitive Study of the Efficacy and Tolerance of Prokinetic Drugs - Metaclopramide and Cinetapride In the Treatment of Functional Dyspepsia - A Randomised Controlled Trial
פירוט הרכיבים הטבעיים שנמצאים ב Cane תוסף תזונה טבעי המסייע לחולי סוכרת להגיע לאיזון ברמות הסוכר שלהם. Cane הוא תוסף תזונה מבית קיורהלייף, חברה הדואגת לאיכות חייהם של החולים במחלות כרוניות.
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What constitutes "Women's Health" issues? All too often this category is hijacked with conversations related exclusively to sex and breast care. In this revealing conversation we review other topics related to women's health and the relationship to "plant based nutrition" and general preventive strategies
Do you know that studies have shown that probiotics goes beyond gut health? Learn more from Dr. Anders Henriksson, Principal Application Specialist through his presentation at the Food for Health Conference held in conjunction with UMass 100th anniversary.
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.
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Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
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
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.
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As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
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These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
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
2. OUTLINE
• INTRODUCTION
• DEFINITION AND MEASUREMENT
• HOMEOSTATIC MECHANISMS CONTROLLING ENERGY BALANCE
• ETIO-PATHOGENESIS OF OBESITY
• TREATMENT OF OBESITY
• PHARMACOTHERAPY OF OBESITY
• HISTORICAL ASPECTS
• CONTEMPORARY ANTI-OBESITY DRUGS
• FUTURE DEVELOPMENTS
• CONCLUSION
21/03/2017 Anti-Obesity Drugs : Dr Sahil Kumar 2
3. INTRODUCTION
• Survival is continuous; Food is intermittent.
• “Globesity” on the rise.
• 2.1 billion people – nearly 30% of the world’s
population – either obese or overweight.
(Lancet. 2014 Aug 30;384(9945):766-81)
21/03/2017 Anti-Obesity Drugs : Dr Sahil Kumar 3
4. INDIAN PERSPECTIVE
• 5% morbidly obese.
• rs12970134
• India’s obesity doubled in last 10 years; Urban-
Rural divide. (NFHS-4, 2015-2016)
21/03/2017 Anti-Obesity Drugs : Dr Sahil Kumar 4
5. DEFINITION AND MEASUREMENT
21/03/2017 Anti-Obesity Drugs : Dr Sahil Kumar 5
Obesity is a state of excess adipose tissue mass.
ICMR
♂:102 cm
(90cm)
♀: 88 cm
(80cm)
6. HOMEOSTATIC MECHANISMS
CONTROLLING ENERGY BALANCE
11/03/2017 Anti-Obesity Drugs : Dr Sahil Kumar 6
• Early 20th Century – hypothalamus damage – wt.
gain.
• 1940s – discrete lesions in rodents – obesity.
• 1953 – hormone from adipose tissue –
hypothalamus.
• Genetic studies in mice – ob (obesity), tub (tubby),
fat, db (diabetes).
• 1994 – Conceptual breakthrough – ob gene cloned;
protein product identified as Leptin.
7. 21/03/2017 Anti-Obesity Drugs : Dr Sahil Kumar 7
• Leptin secreted by adipose cells; acts on hypothalamus.
• Level of Leptin production provides an index of adipose
energy stores.
• “Leptin resistance.”
• The mechanism for leptin resistance is not yet established.
• SOCS3 and PTP1b involved in the leptin resistant state.
12. 11/03/2017 Anti-Obesity Drugs : Dr Sahil Kumar 12
Energy Expenditure
• Energy expenditure is required to maintain
metabolism, physical activity and thermogenesis.
• Symp. Nerv. Sys. (sometimes with thyroid hormone)
in regulation of energy expenditure.
• Both ‘white’ and ‘brown’ fat cells have a major role in
thermogenesis.
• Mitochondrial uncoupling proteins (UCP).
• Noradrenaline (β3), increases PPAR-γ, ↑ UCP-1.
13. 11/03/2017 Anti-Obesity Drugs : Dr Sahil Kumar 13
ETIO-PATHOGENESIS OF OBESITY
• Dietary and socio-cultural factors.
• Genetic susceptibility.
• Specific syndromes.
• Deficiencies in synthesis/ action of leptin.
• Defects in hypothalamic neuronal systems.
• Defects in systems controlling energy expenditure.
• Decreased thermogenesis caused by dysfunction of
proteins that uncouple oxidative phosphorylation.
15. TREATMENT OF OBESITY
•GOAL: To improve obesity-related comorbid conditions
and to reduce the risk of developing future comorbidities.
•Treatment approaches-
1) Lifestyle modification (meal plan, physical activity
and behavioral interventions).
2) Pharmacotherapy.
3) Surgery.
21/03/2017 Anti-Obesity Drugs : Dr Sahil Kumar 15
16. PHARMACOTHERAPY OF OBESITY
AACE/ACE Guidelines (2016)
• Pharmacotherapy - adjunct to lifestyle therapy and not alone.
• Adding pharmacotherapy produces greater wt. loss & wt. loss
maintenance.
• Short-term t/t (3-6 mo) with weight loss medications is not
recommended.
• Consider differences in efficacy, adverse effects, warnings, as well as
weight-related complications and medical history.
• An algorithm for medication preferences that would apply to all
patients cannot currently be scientifically justified.
21/03/2017 Anti-Obesity Drugs : Dr Sahil Kumar 16
17. Indication for Pharmacotherapy
•BMI ≥ 30 kg/m².
OR
•BMI ≥ 27 kg/m²- For patients who have concomitant
obesity-related diseases and for whom dietary and
physical activity therapy has not been successful.
•Drug therapy is adjunctive to lifestyle intervention.
18. PHARMACOTHERAPY: HISTORICAL ASPECTS
21/03/2017 Anti-Obesity Drugs : Dr Sahil Kumar 18
•Soranus of Ephesus (second century AD): Laxatives and
Purgatives.
•1920s and 1930s- Thyroid hormone.
•1933 - 2,4-Dinitrophenol (DNP).
•Late 1930s - Benzedrine. “Rainbow pill" regime.
19. 21/03/2017 Anti-Obesity Drugs : Dr Sahil Kumar 19
• Amphetamines - Second World War. Outlawed - Late 1950s.
•Phentermine (1959) and Fenfluramine (1973).
• 1992 - Fen-phen - 10% weight loss.
• Mid-1990s - Dexfenfluramine (1996).
• Valvular Heart Disease in up to 30% patients.
•1997 - Withdrawal of Fen-phen and dexfenfluramine.
21. ORLISTAT
• Lipostatin (Streptomyces toxytricini).
• MOA: Lipase inhibitor (irreversible).
• PK: Virtually all of it excreted in faeces.
• Dose: 120 mg three times a day.
• A/E: Malabsorption of dietary fat, flatus with
discharge, fecal urgency, fatty/oily stool, and
increased defecation. Fat-soluble vit D and E and
β-carotene.
• Interaction – Cyclosporin.
21/03/2017 Anti-Obesity Drugs : Dr Sahil Kumar 21
22. •Orlistat also reported to be effective in patients suffering
from type 2 diabetes. (Curran & Scott, 2004)
21/03/2017 Anti-Obesity Drugs : Dr Sahil Kumar 22
XENDOS
Torgerson, et al. Diabetes Care, 2004.
23. LORCASERIN
•Lorcaserin- selective 5-HT2C receptor agonist.
•MOA: ↓ food intake through pro-opiomelanocortin.
•Dose: 10 mg Two times a day.
•BLOOM trial: Weight loss was 3.6%.
•No difference in the development of valvulopathy between
drug-treated and placebo-treated participants at 1 year.
•A/E: headache, dizziness, and nausea.
21/03/2017 Anti-Obesity Drugs : Dr Sahil Kumar 23
24. PHENTERMINE-TOPIRAMATE (PHEN/TPM)
• Approved by FDA (2012), not by EMA.
• MOA: Not well understood.
• EQUIP and CONQUER trials: Wt loss 9.3% and 8.6%
respectively.
• Dose: 15mg/90 mg (PHEN/TPM) once a day
• A/E: Paresthesias, dry mouth, constipation,
dysgeusia, insomnia.
21/03/2017 Anti-Obesity Drugs : Dr Sahil Kumar 24
25. NALTREXONE-BUPROPION
•MOA: Combined to dampen the motivation that food
brings (dopamine effect) and the pleasure of eating
(opioid effect).
•In a randomized, double-blind, placebo-controlled trial,
1742 enrolled participants - weight loss = 6.1%.
•Dose = 32 mg/ 360 mg (Naltrexone-Bupropion).
•A/E: Nausea, headache, dizziness, vomiting and dry
mouth.
21/03/2017 Anti-Obesity Drugs : Dr Sahil Kumar 25
26. LIRAGLUTIDE
•Liraglutide, GLP-1 receptor agonist.
•MOA: Weight loss effects via hypothalamic neural
activation causing appetite suppression.
•SCALE™ Obesity and Prediabetes trial: 9.2 % weight loss.
•Dose = 3 mg once daily, injected s/c.
•A/E: Nausea, vomiting, change in bowel habits, acute
pancreatitis.
21/03/2017 Anti-Obesity Drugs : Dr Sahil Kumar 26
27. AGENTS WITHDRAWN IN THE LAST DECADE
•Sibutramine (2010) – ↑ Cardiovascular risks.
•Rimonabant (2008) - Serious psychiatric side effects.
21/03/2017 Anti-Obesity Drugs : Dr Sahil Kumar 27
28. FUTURE DEVELOPMENTS
•Cetilistat - inhibits pancreatic lipase, Phase 3 trials.
•GT 389255 - pancreatic lipase inhibitor and fat-binding
hydrogel polymer. Phase-II.
•TM-38837 - antagonist of the CB1 cannabinoid receptor,
phase I.
•Experimental:
•Inhibit anabolic molecules.
•Stimulate catabolic signals.
•Gastric peptides.
21/03/2017 Anti-Obesity Drugs : Dr Sahil Kumar 28
Leptin was approved in the United States in 2014 for use in congenital leptin deficiency and generalized lipodystrophy
Leptin signals through proopiomelanocortin (POMC) neurons in the hypothalamus to induce increased production of α-melanocyte-stimulating hormone (α-MSH),
requiring the processing enzyme PC-1 (proenzyme convertase 1). α-MSH acts as an agonist on melanocortin-4 receptors to inhibit appetite, and the neuropeptide AgRp (Agouti-related peptide) acts as an antagonist of this receptor. Mutations that cause obesity in humans are indicated by the solid green arrows.
Idiopathic cranial hypertension (pseudotumor)
In patients with type 2 diabetes mellitus who are overweight or obese, antidiabetic medications that have additional actions to promote weight loss (such as glucagon-like peptide-1 [GLP-1] analogs or sodium-glucose-linked transporter-2 [SGLT-2] inhibitors) are suggested, in addition to the first-line agent for type 2 diabetes mellitus and obesity, metformin.
In obese patients with type 2 diabetes mellitus who require insulin therapy, at least one of the following is suggested: metformin, pramlintide, or GLP-1 agonists to mitigate associated weight gain due to insulin. The first-line insulin for this type of patient should be basal insulin. This is preferable to using either insulin alone or insulin with sulfonylurea.
Angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and calcium channel blockers, rather than beta-adrenergic blockers, should be considered as first-line therapy for hypertension in patients with type 2 diabetes mellitus who are obese.
In women with BMI of more than 27 kg/m 2 with comorbidities or BMI of more than 30 kg/m 2 seeking contraception, oral contraceptives are suggested over injectable medications because of weight gain with injectables, provided that women are well informed about risks and benefits (ie, oral contraceptives are not contraindicated).
Anorexiants affect satiety and hunger (the biologic sensation that prompts eating). By increasing satiety and decreasing hunger, these agents help patients reduce caloric intake without a sense of deprivation. The target site for the actions of anorexiants is the ventromedial and lateral hypothalamic regions in the central nervous system. The biologic effect of these agents on appetite regulation is produced by augmentation of the neurotransmission of three monoamines: norepinephrine; serotonin and, to a lesser degree, dopamine. The classic sympathomimetic adrenergic agents (benzphetamine, phendimetrazine, diethylpropion, mazindol, and phentermine) function by stimulating norepinephrine release or by blocking its reuptake. Among the anorexiants, phentermine has been the most commonly prescribed.
Xenical/ Alli- Brand names
Behavioral Modification and Lorcaserin for Overweight and Obesity Management (BLOOM) and Behavioral Modification and Lorcaserin Second Study for Obesity Management (BLOSSOM). weight loss was 3.6% and 3.0%, respectively, in the BLOOM and BLOSSOM trials.
*Agents withdrawn in past decade : Sibu (2010), Rimonabant (2008)
World Obesity Day is observed globally on 11 October with the view of promoting practical solutions to end the global obesity crisis
27th US President William Howard Taft