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THE MEDICAL TREATMENT OF OBESITY - ECHO Ontario
Transcript of THE MEDICAL TREATMENT OF OBESITY - ECHO Ontario
THE MEDICAL TREATMENT OF OBESITY
Session # 1
January 9th, 2020
January 9, 2020
DISCLOSURES
Disclosures:
Grants/Research Support: Novo Nordisk Canada, Valeant, Servier, Sanofi
Speaker’s Bureau/Honoraria: Boehringer-Ingelheim, Eli Lilly, Novo Nordisk Canada, Sanofi,
AstraZeneca, Jansen, Valeant, Bausch Health, Abbott, Sutherland Global Services Canada ULC
Consulting Fees: Boehringer-Ingelheim, Eli Lilly, Novo Nordisk Canada, Sanofi, AstraZeneca,
Jansen, Valeant, Bausch Health, Abbott
Liviu Danescu MD, FACE
These slides were prepared and originally presented by:
Dr. Stephen A. Glazer MD FRCPC FCCP Humber River Regional Hospital
*Slides have been modified for today’s sessionSpecial thanks to Jennifer Brown from the Ottawa BCOE
ACKNOWLEDGEMENTS
1) How do we define obesity?▪ Obesity as a chronic disease
▪ Assessment and management options
2) Patient engagement strategies▪ Bariatric centres of excellence
3) Medications for obesity management▪ Meal replacements: Optifast®
▪ Medications: Orlistat, Liraglutide, Buproprion/Naltrexone
4) Questions
OBJECTIVES
HOW DO WE DEFINE OBESITY?
OBESITY: HISTORICAL APPROACHES
ALT = alanine aminotransferase; BMI = body mass index; FPG = fasting plasma glucose; NAFLD = non-alcoholic fatty liver disease.Adapted from Jensen MD et al. J Am Coll Cardiol. 2014;63:2985-3023; Lau DCW et al. CMAJ. 2007;176:1103-6; CDA Guidelines. Can J Diabetes. 2013;37(suppl 1):S1-212.
Body Mass Index (BMI)
Waist Circumference
Obesity-Related Health risk
Male Female
European, Sub-Saharan African, Eastern Mediterranean and Middle Eastern ≥94 cm ≥80 cm
South Asian, Chinese, Japanese, South and Central American ≥90 cm ≥80 cm
25 to <29.9 30 to <34.9 35 to <40 ≥40
Overweight Class I Class II Class III
Obesity
Diabetes FPG, A1c
Hypertension Blood pressure (BP)
Dyslipidemia Lipid profile
NAFLD ALT
Edmonton Obesity Staging System (EOSS) or King’s Criteria
Looks at the health and complication-based conditions (medical,mental and functional) not size or weight alone
OBESITY: NEW APPROACHES
FACTORS AFFECTING WEIGHT
http://kim.foresight.gov.uk/Obesity/Obesity.html
Biology
Food Production
Food Intake
Social InfluencesIndividual Physiology
Individual Activity
ActivityEnvironment
OBESITY IS A CHRONIC DISEASE
CMA. CMA recognizes obesity as a disease. 2015. https://www.cma.ca/En/Pages/cma-recognizes-obesity-as-a-disease.aspx.
Canadian Medical Association (CMA) declared obesity a chronic disease in 2015 ▪ Multiple factors contributing to body weight
(genetics, physiology/metabolism, environmental, psychosocial, etc)
▪ Excessive adipose tissue affecting health (medical, mental and functional health)
▪ Other organizations have also declared obesity a chronic disease: ▪ American Medical Association (AMA)
▪ World Health Organization (WHO)
▪ World Obesity Foundation (WOF)
OBESITY IS A COMPLEX CHRONIC DISEASE
CHF = congestive heart failure; GERD = gastroesophageal reflux disease; PCOS = polycystic ovarian syndrome.1. Catenacci VA et al. Clin Chest Med. 2009;30:415-444. 2. Wang C et al. Diabetes Care. 2011;34:1669-1675. 3. Lauby-Secretan B et al. N Engl J Med. 2016;375:794-798.
HEALTH BENEFITS OF WEIGHT LOSS
Cefalu et al. Diabetes Care. 2015; 38:1567-1582.
OBESITY: EXPECTATIONS
Adapted from www.drsharma.ca & Ryan et al. Arch Intern Med. 2010 Jan 25;170(2):146-54.
MANAGING WEIGHT IS TRICKY
Thermogenic Adaptation
▪ Energy expenditure ↓ after weight loss
▪ Homeostatic drivers in brain adapt to want to conserve energy and increase body weight
Hormonal Adaptation
▪ Hunger hormones ↑▪ Satiety hormones ↓▪ Desire to eat highly
palatable foods ↑▪ All to defend against
weight loss (adipose loss)
Body weight conservation (adipose tissue): evolutionary protective mechanism to defend against weight loss
Morton GJ, et al. Nature. 2006;443:289-295. Leibel RL, et al. N Engl J Med. 1995;31:621-628. Schwartz A & Doucet É. Obes Rev. 2010;11:531–547. Sumithran P et al. N Engl J Med. 2011;365:1597–1604.
PATIENT ENGAGEMENT
STRATEGIES
MYTHS SURROUNDING OBESITY:THE LIVED EXPERIENCE
“Food causes obesity”
“Obesity is a choice”
“Calories in, calories out”
“Who cares about why?Just eat less”
“It’s just a lack of will power”
UNDERSTAND & LISTEN
Ask for permission to discuss their weight and explore readinessAsk
Assess health status, obesity-related risks (BMI + EOSS) and root causes to their weight gain (metabolic, functional, mental health, environment) Assess
Advise on health risks and benefits of treatment options.
Aim for focus on improving HEALTH rather than simply weight lossAdvise
Agree on health outcomes and behaviour-related goalsAgree
Assist in accessing appropriate resources, providers, programs to support patients goals/behavioursAssist
Refer to the 5A‘s of Obesity Management for research and resources on use in Primary Care: https://obesitycanada.ca/resources/5as/
EXPECTATION MANAGEMENT: ALIGNING HCP/PATIENT EXPECTATIONS
HCP = healthcare professional.
Foster et al. Am J Clin Nutr. 2005;82(suppl):230S-235S.
-5-10%- 30%
Patient Expectations HCP Expectations
▪ Discuss patient goals prior to treatment to identify unrealistic expectations
▪ Discuss biological/physiological limitation
▪ Shift goals beyond weight loss▪ Improvement in metabolic and
cardiovascular measures▪ Improvements in quality of life measures
COUNSELLING WITHOUT PERCEIVED JUDGEMENT IMPROVES PATIENT OUTCOMES
Patients who received weight-management
counseling were
5xmore likely to attemptweight loss than those
who did not, and achieve clinically
significant weight loss
Patients who did notperceive judgment
during counseling were more likely to achieve
≥10% weight loss compared with patients who did
perceive judgment
aA US cross-sectional, internet-based survey in 600 adults with overweight/obesity (BMI ≥25 kg/m2) to assess differences
in weight-loss attempts and clinically significant weight loss (≥10%) based on receipt of HCP counseling and perceived judgment.
BMI = body mass index; HCP = health care professional.
Gudzune KA et al. Prev Med. 2014;62:103-107.
PUTTING THE PATIENT FIRST
DO SAY OR WRITE
DON’T SAY OR WRITE
“Patients living with…”
▪ Obesity▪ A higher weight▪ Weight problems
▪ Obese ▪ Fat*▪ Extremely obese▪ Super or morbid obese
~20%of patients who perceive weight stigma from their
health care provider would avoid future
appointments or seek out a new health care
provider
Obesity Action Coalition. http://www.obesityaction.org/wp-content/uploads/People-First.pdf. Accessed July 20, 2016; 2. Puhl R et al. Int J Obes (London). 2013;37:612-619.
CANADIAN CENTRES OF EXCELLENCE IN BARIATRIC MEDICINE
HOSPITAL MEDICAL PROGRAMS
Case Management
•Patient assessment by physicians or nurse practitioner with expertise in bariatric medicine
Registered Dietitian
Social Worker, Psychologist or Behaviourist
Kinesiologist, Exercise Physiologist, Physiotherapist, Occupational Therapist
Access to pharmacotherapy counselling
MEDICATIONS FOR OBESITY
MANAGEMENT
WHEN IS PHARMACOTHERAPY APPROPRIATE?
Pharmacotherapy (Based on 2006 CPG)
BMI ≥27 kg/m2 + risk factors orBMI ≥30km/m2
Adjunct to lifestyle modifications consider if patient has not lost 0.5kg (1lb) per week by 3 – 6 months after lifestyle changes
UPDATED Canadian CPG for
Obesity Management coming
early 2020
ORLISTAT
1.Heck et al. Pharmacotherapy. 2000; 20(3): 270-279. 2. Hadvary et al. Biochem J. 1988; 256:357-361. 3. Borgstrom et al. Biochim Biophys Acta. 1998; 962:308-316. 4. Hadvary et al. J Biol Chem. 1991; 266(4):2021-2027. 5.Ransac et al. Eur J Biochem. 1991; 202:395-400.
▪ Pancreatic and gastric lipase inhibitor
▪ Naturally produced by Stephomyces toxytricini
▪ Mechanism of action: ▪ Forms covalent bond with active serine site of gastric and
pancreatic lipases in lumen of GI tract
▪ Prevents enzymes from hydrolyzing dietary fat (triglycerides) into absorbable free fatty acids and monoglycerols
▪ Undigested triglycerides are eliminated in feces
▪ Lipase inhibition decreases dietary fat absorption (contributing to lower caloric intake → weight loss)
▪ Peripheral administration of GLP-1 receptor agonists ▪ Reduces short term oral intake
▪ Promotes satiety
▪ Decreases energy intake
▪ Net effect = decreases body weight
▪ Mechanisms of action: ▪ GLP-1 receptors are expressed in the stomach on gastric parietal
cells
▪ Interact with receptors localized to hypothalamic CNS centers that
regulate eating behaviors
▪ Activating neurons in the CNS coupled to gastrointestinal motility
and gastric emptying (ascending neural pathways; vagal afferent
fibers)
LIRAGLUTIDE
1. Shaefer et al. Postgrad Med. 2015; 127(8): 818-826; 2. Elrick et al. J Clin Endocrinol Metab. 1964; 24:1076-1082; 3.Baggio et al. Gastroenterology. 2007; 132: 2131-2157; 4.Nauck et al. J Clin
Endocrinol Metab. 1986;63:492-498; 5.Baggio et al. J Clin Invest. 2014;124(10):4223-4226.
COMBINATION: NALTREXONE AND BUPROPION
1. Naltrexone product information; 2. Wellbutrin SR Product Information.
The hypothalamus (hunger center) to reduce hunger
The mesolimbic reward system to help control cravings
REGULATION OF HUNGER: ROLE OF HYPOTHALAMIC POMC NEURONS
1. Billes SK et al. Pharmacol Res. 2014;84:1-11. 2. Modi, Renuca. Pharmacotherapy III: Contrave for Chronic Weight Management
Hypothalamus
POMC neurons▪ Integrate multiple energy
balance signals
POMC stimulus
POMC neuron
β-endorphin (endogenous opioid)
▪ Released from POMC neuron with α-MSH▪ Binds to µ-opioid receptor to increase food intake and conserve energy (negative feedback
loop)
µ-opioid receptorPOMC negative feedback loop
↓ Appetite↑ Energy Expenditure
α-MSH
MC4-R
α-MSH▪ Released from POMC neuron▪ Binds to MC4-R to decrease food
intake
SYNERGISTIC ACTION OF NALTREXONE & BUPROPION TO ACTIVATE POMC NEURONS TO SUPPRESS APPETITE
1. Billes SK et al. Pharmacol Res. 2014;84:1-11. 2. Modi, Renuca. Pharmacotherapy III: Contrave for Chronic Weight Management
Figure adapted from Billes et al,1 © 2014, and Modi R2, 2018
Hypothalamus
POMC neuron
↑ POMC activity ↓ Hunger↓ Weight
Directly ↑ POMC activity
Indirectly ↑ POMC activity
CHOOSING A MEDICATION: CONTRAINDICATIONS
Orlistat
• Chronic Malabosprtion, Cholestasis, Cyclosporin
Liraglutide
• PHx/FHx medullary thyroid Ca, Multiple endocrine neoplasia syndrome type 2 (MEN2)
• Females – actively trying to conceive
Bupropion/Naltrexone
• HTN, Seizures, Eating Disorder(s), Severe Hepatic Impairment, End-stage Renal Failure
• Use of opiods or opioid agonists, Thioridazine, MAOIs, Tamoxifen
• Abrupt d/c of etoh, sedative and/or antiepileptic drugs
CHOOSING A MEDICATION: CAUTIONS
Orlistat
▪ Nephrolithisais (Ca oxalate)
Liraglutide
▪ Pancreatitis, Gallstones, Arrhythmias
Bupropion/Naltrexone
▪ CYP2B6 inhibitors: Clopidogrel, ticlopidine
▪ Inhibits CYP2D6: SSRI, SNRI, B-Blockers, Type 1 C Antiarrhythmic (proprafenone, flecainaide)
▪ Anxiety, Insomnia, Arrhythmia
CHOOSING A MEDICATION: PATIENT CONSIDERATIONS
Considerations Orlistat Liraglutide Bupropion/Naltrexone
ComorbiditiesPre-diabetesConstipationDyslipidemia
Pre-diabetesType 2 Diabetes
SmokerDesire to decrease ETOH
Depression
Hunger None Yes Yes
Cravings None None to Mild Mild to Strong
▪ Obesity is a complex, chronic disease defined by having excess or abnormal adipose tissue that impairs health
▪ Use comprehensive medical assessment of health factors (medical, mental and functional health) → EOSS instead of BMI alone
▪ Use 5As to obesity management
▪ Medications can be part of obesity management
▪ Lifelong management
SUMMARY
QUESTIONS &
DISCUSSION
REFERENCES
Jensen MD et al. J Am Coll Cardiol. 2014;63:2985-3023;
Lau DCW et al. CMAJ. 2007;176:1103-6;
CDA Guidelines. Can J Diabetes. 2013;37(suppl 1):S1-212
NCD Risk Factor Collaboration. Lancet. 2016;387:1377-96.
NCD Risk Factor Collaboration. http://www.ncdrisc.org/d-adiposity.html.
Twells et al. CMAJ OPEN. 2014; 2(1): 18-26.
Thomas CE et al. Obesity. 2016;24:1955-1961.
Catenacci VA et al. Clin Chest Med. 2009;30:415-444.
Wang C et al. Diabetes Care. 2011;34:1669-1675.
Lauby-Secretan B et al. N Engl J Med. 2016;375:794-798.
Mathew B, et al. J Am Board Fam Med. 2008;21:562-568.
Mokdad AH, et al. JaMA. 2003;289:76-79.
Billes SK et al. Pharmacol Res. 2014;84:1-11.
Hollander P, et al. Diabetes Care. 2013;36:4022-4029.
Apovian CM, et al. Obesity..13;21:935-943
Luppino FS, et al. Arch Gen Psychiatry. 2010;67:220-229.
Parkin DM, et al. Br J Cancer. 2011;105(suppl 2):S77-S81
Calle, EE., et al. N Engl J Med. 1999;341:1097-1105.
CMA. CMA recognizes obesity as a disease. 2015. https://www.cma.ca/En/Pages/cma-recognizes-obesity-as-a-disease.aspx.
Whitlock G, et al. Lancet. 2009;373:1083-1096
Garvey WT, et al. [published online May 24, 2016]. Endocr Pract.
Jensen, MD et al. Circulation 2014: 129;5102-38.
National Heart, Lung, and Blood Institute. 2002. https://www.nhlbi.nih.gov/files/docs/resources/heart/steps.pdf. Accessed July 26, 2016.
Obesity Society. http://www.obesity.org/obesity/resources/facts-about-obesity/infographics/potential-contributors-to-obesity. Accessed April 4, 2017.
Foster et al. Am J Clin Nutr. 2005;82(suppl):230S-235S.
CONTRAVE [product monograph], February 12, 2018, Valeant Canada LP; Laval, QC.
Obesity Action Coalition. http://www.obesityaction.org/wp-content/uploads/People-First.pdf. Accessed July 20, 2016; 2. Puhl R et al. Int J Obes (London). 2013;37:612-619.
Gudzune KA et al. Prev Med. 2014;62:103-107.
Morton GJ, et al. Nature. 2006;443:289-295. 2. Leibel RL, et al. N Engl J Med. 1995;31:621-628.
Schwartz A & Doucet É. Obes Rev. 2010;11:531–547.
Sumithran P et al. N Engl J Med. 2011;365:1597–1604.
Rosenbaum M et al. Am J Physiol Regul Integr Comp Physiol. 2003;285:R183–R192.
Rosenbaum M & Leibel R. L. Int J Obes (Lond). 2010 October ; 34(0 1): S47–S55.
Ryan et al. Arch Intern Med. 2010 Jan 25;170(2):146-54
Lau, et al. 2006 Canadian clinical practice guidelines on the management and prevention of obesity in adults and children. CMAJ. 2007;176(8 suppl):Online-1-117.
Heck et al. Pharmacotherapy. 2000; 20(3): 270-279
22
REFERENCES
Hadvary et al. Biochem J. 1988; 256:357-361.
Borgstrom et al. Biochim Biophys Acta. 1998; 962:308-316.
Hadvary et al. J Biol Chem. 1991; 266(4):2021-2027.
Ransac et al. Eur J Biochem. 1991; 202:395-400.
Xenical (product monograph), November 18, 2015, Hoffmann-La Roche Limited, Mississauga, ON.
Shaefer et al. Postgrad Med. 2015; 127(8): 818-826
Elrick et al. J Clin Endocrinol Metab. 1964; 24:1076-1082
Baggio et al. Gastroenterology. 2007; 132: 2131-2157
Nauck et al. J Clin Endocrinol Metab. 1986;63:492-498
Baggio et al. J Clin Invest. 2014;124(10):4223-4226.
Saxenda (product monograph), July 12, 2017, Novo Nordisk Canada Inc, Mississauga, ON.
CONTRAVE [product monograph], February 12, 2018, Valeant Canada LP; Laval, QC.
Naltrexone product information; Wellbutrin SR Product Information.
Greenway FL, et al. Lancet. 2010;376:595-605;3. Wadden TA, et al. Obesity. 2011;19:110-120
2
REFERENCES