2 MARC-ANDRE CORNIER, MD - Program Chairman Investigations StratificationFront Line Clinical ApplicationsNew Frontiers and Emerging Treatment Paradigms for Optimizing Management of ObesityFocus on Multimodal Interventions for Weight Loss and Novel Pharmacological Strategies Targeting the Central Nervous SystemMARC-ANDRE CORNIER, MD - Program ChairmanAssociate Professor of MedicineDivision of Endocrinology, Metabolism and DiabetesAnschutz Health and Wellness CenterUniversity of Colorado School of MedicineDenver, CO
3 Distinguished Faculty MARC-ANDRE CORNIER, MD - Program ChairmanAssociate Professor of MedicineDivision of Endocrinology, Metabolism and DiabetesAnschutz Health and Wellness CenterUniversity of Colorado School of MedicineDenver, COREKHA KUMAR, MD, MSDiabetes, Endocrinology and MetabolismWeill Cornell Medical CollegeAssistant Professor of MedicineNew York Presbyterian HospitalNew York, NYROBERT J. MALCOLM, MDProfessor, Department of Psychiatry and Behavioral SciencesAssociate Dean for Continuing Medical Education, College of MedicineMedical University of South CarolinaCharleston, SC
4 MARC-ANDRE CORNIER, MD - Program Chairman Investigations StratificationFront Line Clinical ApplicationsCurrent Challenges and Barriers to Optimizing Management of ObesityA Year 2014 Status Report for the Primary Care Physician and Clinical SubspecialistMARC-ANDRE CORNIER, MD - Program ChairmanAssociate Professor of MedicineDivision of Endocrinology, Metabolism and DiabetesAnschutz Health and Wellness CenterUniversity of Colorado School of MedicineDenver, CO
5 Obesity by the Numbers Overweight U.S. adults: 67% U.S. adults with obesity: 33%U.S. children with obesity: 17%Annual U.S. health care expendituresfor obesity: > $ 200 billionU.S. consumer expenditures forweight loss products: > $ 50 billionDaily deaths from obesity complications > 1,000
6 Disproportionate Increase in Severe Obesity Today, more than 1.7 million US adults with BMI>50Sturm R, Pub Health, 2007
7 Complications of Obesity PsychologicalNeoplasticInflammatoryStructuralMetabolicDegenerative65+
8 Long-term Control of Obesity – 2013 1% =750,000U.S. adults
9 Obesity is Counterintuitive Hides in plain sightMost obesity NOT recognized by physicians or the publicNOT mainly in AmericaNOT simply a problem of eating too muchNOT a single disorder – very heterogeneousPossibly 100 or more clinically meaningful subtypesThis recognition is essential to solving the problem
10 Cause of Obesity Historical view Current perspective Lifestyle choice Characterological flaw (willpower, psychology)Current perspectiveComplex physiologyEpidemic from changes in modern environmentGenetic Predisposition (physiology) in the wrong environmentWidely recognized as a diseaseHuge burden of associated illness – a cause of more than 60 medical disorders (including 12 types of cancer)Devastating effect on efficacy and quality of life
11 Weight and Energy Balance By the laws of physics…FoodIntakeEnergyExpenditure
12 The Normal Physiology of Energy Balance Average adults consume kcal/dayAverage adults therefore consume 2-3 times as much food as requiredExcess intake is available for physiological emergenciesMaintaining weight within 20 lbs. between ages 21 and 65 requires matching of intake and expenditure within 0.2%Corresponds to accuracy of 4-5 kcal/dayLess than one-half potato chipMaintenance of normal fat stores (and body weight) requires precise disposal of 60-70% of ingested calories dailyThus, daily energy balance is likely an evolved physiological trait largely independent of cultural or behavioral differences.
13 Obesity: A Failure of Weight Regulation Adipose tissueLeptinHTFood intakeEnergy expenditureNutrient handlingCortexGI TractGeneticsEnvironmentAltered food supplyReduced physical activityStressDrugsOthers?
14 Barriers, Challenges and Opportunities to Obesity Management Our biologyFavors fat storageCan this be manipulated?EnvironmentMacroenvironment – more difficult to changeMicroenvironment – can be changed by the individual?Health Care SystemLack of “buy in” from providers, patients and insurersOthers?
15 Investigations Stratification Front Line Clinical ApplicationsEpidemiology and Clinical Approaches to Obesity Management What Do Trials, Algorithms, and Clinical Experience Teach Us About Sequencing Treatment Approaches for Obesity?REKHA KUMAR, MD, MSDiabetes, Endocrinology and MetabolismWeill Cornell Medical CollegeAssistant Professor of MedicineNew York Presbyterian HospitalNew York, NY
16 Obesity Diagnosis Obesity is defined an excess of body fat Body fat is difficult to measure cheaplyFor people with average lifestyles, Body Mass Index (BMI) has been the measure of obesityBMI = Wt in Kg divided by height in M squaredBMI has been divided into categories18-25 is normal, is overweight, is class I, is class II, >40 is class III
17 Relationship Between Mortality and BMI 2.52.01.51.0MenWomenMortality RatioVeryLowVeryHighLowModerateHighBody Mass Index, kg/m2Data from Lew EA: Mortality and weight: insured lives and the American Cancer Society studies. Ann Intern Med 103: , 1985.
20 BMI Classes are Poor at Estimating Risk The BMI classes assume that mortality and morbidity is proportional to BMIThis is not necessarily true. There are very obese people who are otherwise healthy.In other chronic diseases like cancer there is a staging system to estimate riskAn obesity staging system may be a better approach to estimating medical risk of obesity
21 EOSS Predicts Mortality in NHANES III Padwal R, Sharma AM et al. CMAJ 2011
22 Edmonton Obesity Staging System (EOSS) Stage 2co-morbiditymoderateend-organ damageseverepre-clinical risk factorsmildStage 1Stage 3end-stageObesityStage 0Stage 4absentabsentabsentMentalMedicalFunctionalSharma AM & Kushner RF, Int J Obes 2009
23 Edmonton Obesity Staging System Stage 0: No obesity related risk factorsStage 1: Subclinical risk factors – borderline HTN or DM, minor aches or psychopathologyStage 2: Established obesity-related disease – HTN, DM, PCO, moderate limitations ADLStage 3: Established organ damage – MI, CHF, DM comp, significant limitations of ADLStage 4: Severe disabilities – end stage and limitations like wheelchair useSharma AM and Kushner RF. Int J Obes ;33:289-95
24 EOSS Predicts Mortality at Every BMI Level NHANES III OverweightPadwal R, Sharma AM et al. CMAJ 2011
25 EOSS Distribution Across BMI Categories NHANES III (1988-1994) Overweight23 million10 millionClass III50 million6 millionPadwal R, Sharma AM et al. CMAJ 2011
26 Obesity is Leveling in Prevalence The prevalence of obesity in 1961 was 10% in men and 15% in women defined as BMI >30Obesity prevalence started to rise in 1980The prevalence of obesity is now leveling off at 35.5% of the population.The prevalence of diabetes follows the prevalence of obesity by approximately 10 yearsDiabetes prevalence started to rise in 1990
28 Work Related Physical Activity is Falling Church TS et al. Plos One.2011;6(5):e19657
29 Fall in Energy Expenditure at Work Mean OccupationRelated METsYearEnergy Expenditure (calories)Occupation Related DailyYearChurch TS et al. Plos One.2011;6(5):e19657
30 Weight Gain Predicted by Activity et al. Plos One.2011;6(5):e19657
31 What is Causing the Epidemic People are less active and are eating moreThere are many causes. We cannot just scapegoat fast foodObesity virus – Adenovirus D-36 is one causeEndocrine disruptors have been suggestedRegardless of the cause, eating less and being more active will help – you will hear more in this seminar on ways to accomplish that.
32 Another Cause of Obesity Adenovirus of D group 36 (AD-36) causes obesity in non-human primates but one cannot intentionally infect humansAD-36 antibodies: 30% of obese and 11% leanIn identical twins discordant for antibodies, the positive twin had 2.1% more fat and had a BMI 1.4 units higher (p<0.03)This is insulin sensitive obesity with lower cholesterol and triglyceridesAtkinson RL et al. Int J. Obes ;29(3):281-6
33 Is Obesity Prevalence Important? Obesity is stigmatized especially in women and causes psychological distress.Obesity is associated with diabetesObesity is associated with hypertension and heart diseaseObesity is associated with cancerObesity is associated with osteoarthritis and much disability.
34 The Prevalence of Diabetes in the US CDC website
35 DiabetesThe prevalence of diabetes has tripled since the 1980’s and is increasingIt is estimated that 8.2% of the US population had Type 2 diabetes in 2010 and it is predicted that 10.8% will have Type 2 diabetes by 20200.2% of the population have type 1 diabetes and 3.1% have undiagnosed diabetes28.4% of the US has pre-diabetes
36 Diabetes is ExpensiveIt is estimated the diabetes costs the US health care system $194 billion in 2010 and will cost an estimated $500 billion in 2020.The US will spend approximately $3.4 trillion in the next decade on diabetes-related careThe expense of diabetes and those associated obesity-related diseases like cancer, cardiovascular disease and others are and will stress our health care delivery system
39 Mortality Risk with Staging System ****HR for All CauseHR for All CVDRefRefKuk JL et al. Appl Physiol Nutr Metab ;36:
40 Association Between EOSS and Mortality Risk in Aerobics Center Longitudinal Study (n = 29 533) Kuk JL, et al. Appl. Physiol. Nutr. Metab. 2011;36: 570
41 Obesity Related Disease Improves with Weight Loss Sjostrom L et al. N Engl J Med ;357(8):741-52
42 Summary Obesity can be diagnosed by class and stage People in the US are less active and eating more, but multiple causes for obesity existComplications of obesity include diabetes, heart disease, cancer and increased mortalityObesity is expensive and straining our health care delivery systemIt is of utmost importance to screen for obesity and intervene in its management
43 Investigations Stratification Front Line Clinical ApplicationsRegulating Energy Balance: The Pivotal Role of the Central Nervous System in Appetite Regulation Focus on 5HT2c Receptors and Other CNS Signaling Systems Controlling Neuroregulation of Energy BalanceROBERT J. MALCOLM, MDProfessor, Department of Psychiatry and Behavioral SciencesAssociate Dean for Continuing Medical Education, College of MedicineMedical University of South CarolinaCharleston, SC
44 Weight Regulating Mechanisms and Effect of Anti-obesity Drugs – Its Complicated! Endogenous Signaling of Appetite-regulating Hormones, Neuropeptides, and Neurotransmitters, and The Drugs That Target These PathwaysValentino MA, Lin JE, Waldman SA. Clin Pharm & Therapeutics (2010) 87 6, 652–662. doi: /clpt
45 Biological Susceptibilities Etiology of ObesityENERGYEXPENDITURESedentaryLifestyleENERGYEtiology of ObesityObesity occurs when the body’s energy intake is out of balance with its expenditure over an extended period.The balance can be upset either by increased intake (eg, through a high-fat, high-calorie diet) or decreased expenditure (eg, through a sedentary lifestyle). A genetic predisposition to obesity accelerates the process.Treating obesity involves shifting the balance so that expenditure exceeds intake.INTAKEHigh EnergyGenetic &Dense FoodsBiological Susceptibilities(sugar or fat)(Underlying basis)
46 Feedback Model Controller Afferent Signals Controls Efferent Fat ControlledSystem
47 Feedback Model Controller Afferent Signals Controls Efferent Fat AnatomyMonoaminesPeptidesCytokinesAfferentSignalsControlsEfferentFatControlledSystem
48 Picture of Frohlich’s Case of Hypothlamic Obesity
49 Location of Hypothalamic Centers That Affect Feeding ThalamusMamillo-thalamicTrackDorsal HyopthalmusDorsomedial HypoLateral HypoSurap-optic nucleusVentromedial HypoLaVentromedialHypothalamicLesionsLateral HypothalamicLesions
50 Feedback Model Controller Afferent Signals Controls Efferent Fat AnatomyMonoaminesPeptidesCytokinesAfferentSignalsControlsEfferentFatControlledSystem
52 Serotonin Biology - ISerotonin is most concentrated in the hypothalamus, basal ganglia and brainstem7 groups of 14 serotonin receptors are known5HT-1 - Intronless, G-protein coupled receptor that inhibits adenylyl cyclase5HT-2Contains introns, that are coupled to G-protein receptors that activate phospholipase C5-HT2C is only in the brain5HT-3 - Ligand-gated ion channel
53 Serotonin Biology - IIActivation of 5-HT1A auto-receptor increases feedingActivation of 5-HT1B and 5-HT2C by any 5-HT agonist will reduce food intake5-HT receptors in PVN specifically decrease fat intakeKnock-out of 5-HT2C receptor produces obesity and convulsions.Serotonin reuptake inhibitors and releasers can precipitate weight loss or weight gain
54 Serotonin (and Other Agonists) in PVN Reduce Food Intake141210Saline8Serotonin2-Hr Food Intake (kcal)642CarbohydrateFatProteinMacronutrient ChoiceSmith B et al AJP 1999
55 Mice lacking 5-HT 2C receptors have hepatic insulin resistance 5-HT2CRs Expressed by Pro-opiomelanocortin Neurons Regulate Insulin Sensitivity in LiverMice lacking 5-HT 2C receptors have hepatic insulin resistanceWhich is normalized by re-expression of 5-HT(2C) receptors only in pro-opiomelanocortin (POMC) neuronsEvidence that 5-HT2C Rs expressed by POMC neurons are physiologically important in regulating hepatic glucose production and insulin sensitivityMoreover, this 5-HT2C R-melanocortin circuit is sufficient to mediate the anti-diabetic effects of 5- HT2CR agonists.Xu Y, et al Nat Neurosci Dec;13(12): Epub 2010 Oct 31
56 Serotonin 2c Receptor and Diabetes POMC –Serotonin 5-HT2cHypothalamusInsulin resistanceLiverIntestines, Fat cells and the rest of the body sending up signals to stop eating
57 Serotonin Interacts with Melanocortin Pathways Regulating Energy Homeostasis Anorectic serotonin (5-HT) drugs activate pro- opiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus.A serotonin 2C receptor is expressed on POMC neurons and contributes to this effect.Hypophagia induced by serotonin (5-HT) is attenuated by either pharmacological or genetic blockade of downstream melanocortin 3 and 4 receptors.Heisler LK, Dowley MA Kishi T. Ann N Y Acad Sci Jun;994:
58 Serotonin and Melancortin Receptors We conclude that serotonin (5-HT) drugs require functional 5-HT2C receptors in the POMC that modulate melanocortin pathways to exert their effects on food intake.In animals without serotonin receptors, replacement specifically in the POMC neurons restores suppression of insulin by CNS serotoninHeisler LK, Dowley MA Kishi T. Ann N Y Acad Sci Jun;1994:169-74.
59 Mean Weight Loss (% Initial Weight) INDEX Study Completersdexfenfluramine n = 248placebo n = 221months124681012-3-6-8-12Treatment X Time Interaction To T12 p<0.001 / T6 T12 p<0.01p<0.01Mean Weight Loss (% Initial Weight)Guy-Grand et al INDEX study Lancet 1988
60 Phentermine: A Noradrenergic Drug Reduces Body Weight Time in WeeksContinuous PhentermineAlternate Phentermine & PlaceboPlacebo510Weight loss (kg)Weight loss (lbs)Munro JF et al BMJ 1968;1:352-4
61 Feedback Model Controller Afferent Signals Controls Efferent Fat AnatomyMonoaminesPeptidesCytokinesAfferentSignalsControlsEfferentFatControlledSystem
62 Peptides That Affect Food Intake IncreaseDecreaseAgouti-related peptideDynorphinGhrelinMelanin-concentrating hormoneNeuropeptide YOrexin A (Hypocretin)RF-2 peptides (arginine phenylalanine amide-2)Galanin-like-peptideα-MSHCorticotrophin-releasing hormoneCholecystokininCocaine-amphetamine regulated transcriptGlucagon-like peptide-1LeptinAmylinBombesin/GRPObestatin (part of ghrelin)Nesfatin-1 (NEFA-NUCB2)
63 Peptides That Affect Food Intake IncreaseDecreaseAgouti-related peptideDynorphinGhrelinMelanin-concentrating hormoneNeuropeptide YOrexin A (Hypocretin)RF-2 peptides (arginine phenylalanine amide-2)Galanin-like-peptideα-MSHCorticotrophin-releasing hormoneCholecystokininCocaine-amphetamine regulated transcriptGlucagon-like peptide-1LeptinAmylinBombesin/GRPObestatin (part of ghrelin)Nesfatin-1 (NEFA-NUCB2)
64 Leptin the Ultimate Messenger of Fat Stores POMC –Serotonin 5-HT2cHypothalamusWeight LossLeptinFat CellsIntestines, Liver, Pancreas and the rest of the body sending up signals to stop eating
65 Model of the Arcuate Nucleus Model showing the afferentsignals from the peripherythat modulate the activityof hypothalamic neurons ina reciprocal way to increaseor decrease food intakeBadman, Science 2005
66 Feedback Model Controller Afferent Signals Controls Efferent Fat AnatomyMonoaminesPeptidesCytokinesAfferentSignalsControlsEfferentFatControlledSystem
67 Obesity Is Associated with Inflammatory Hypothalamic Injury“….Consumption of a High Fat Diet rapidly induces neuronal injury in a brain area critical for energy homeostasis.“Thaler, J et al, J Clin Invest Jan 3;122(1):
68 Hypothalamic Inflammatory Markers Increase on High Fat Diet Data are after 3 daysof eating a high fat diet2.02.0mRNA (fold increase)1.51.00.5Il1-b Il Tnf-α Socs3 Nfkb IkBkb IkBkθInflammatory MarkersThaler JP et al J Clin Invest 2012;122:
69 Obesity Is Associated with Inflammatory Hypothalamic Injury “….Consumption of a HFD rapidly induces neuronal injury in a brain area critical for energy homeostasis.““In human beings there is MRI evidence for gliosis in the hypothalamus of obese humans.”“Collectively, this work identifies a potential link between obesity and hypothalamic injury in humans as well as animal models.”Thaler, J et al, J Clin Invest Jan 3;122(1):
70 Leptin Resistance and Cytokines “Taking all of these phenomena into account, we think that it is possible that overconsumption of nutrients could be a reason for development of leptin resistance”“This line of thinking favors the fact that increased adiposity and consequent hyperleptinemia decreases the leptin action and creates the leptin resistance”Ergin A, Cell Metabolism 2008;12:2004
71 Does This Explain How Something Environmental Turns Into Something “Physical?” High fat diets and inflammationEvidence of apoptosis and glial ensheathment of ARC neurons in animals rendered obese by chronic HFD feeding.Moreover, these responses were detected specifically in ARC POMC cells25% reduction in the number of hypothalamic POMC neuronsMice chronically fed a HFD.POMC cells play an essential role to protect against obesityLoss of these cells is sufficient in and of itself to cause excess weight gain in miceFattening Foods Cause Dropout of POMC Neurons and Glial Ensheathment of ARC Neurons. Does That Explain Why It’s So Hard To Lose Weight?
74 Weight Regulating Mechanisms and Effect of Anti-obesity Drugs – It’s Complicated! Endogenous Signaling of Appetite-regulating Hormones, Neuropeptides, and Neurotransmitters, and The Drugs That Target These PathwaysValentino MA, Lin JE, Waldman SA. Clin Pharm & Therapeutics (2010) 87 6, 652–662. doi: /clpt
75 Treatment Gap in the Management of Obesity QNEXA_Core_ _v03_NO_HIDDEN.pptTreatment Gap in the Management of Obesity4/13/2017Physicians Need Effective Pharmacotherapies That Will Reduce Weight Significantly and Reduce Weight-related ComorbiditiesCurrentPharmacotherapyToo risky for many peopleLap BandGastric BypassTreatmentGapBetween diet and exercise and the current pharmacotherapy on one hand, and bariatric surgery on the otherWe need more treatments to fill the treatment gap, treat people in whom surgery is not indicatedIn hypertension we have 100 medications in 9 categories,0% 5% 10% 15% 20% 25% 30% 35%What will fill the gap ?New meds, combos, less invasive surgeryQNEXA
76 MARC-ANDRE CORNIER, MD - Program Chairman Investigations StratificationFront Line Clinical ApplicationsNew Frontiers and Treatment Paradigms for Pharmacologic Management of Obesity Focus on Safety and Efficacy of Agents Affecting CNS Signaling Systems and Appetite RegulationMARC-ANDRE CORNIER, MD - Program ChairmanAssociate Professor of MedicineDivision of Endocrinology, Metabolism and DiabetesAnschutz Health and Wellness CenterUniversity of Colorado School of MedicineDenver, CO
77 Overall Treatment Strategy Typical Algorithm(Progress through algorithm as clinically required)Self-directed Lifestyle ChangeProfessionally-directed Lifestyle ChangeAdd MedicationsWeight Loss SurgeryPost-surgical Combination Therapies
79 Where Have We Been? Where Are We Going? Obesity: A physiologically controlled chronic disease.Medications work when taken.Safety and benefit issues with obesityThe evolution of chronic disease medicationsDrugs recently approvedDrugs in late developmentObesity drugs in the future
81 Chronic Disease Drug Development HypertensionObesityOrlistat – calories in stoolCNS drugs – side effects eg. amphetamine and addictionCombinations to lower side effects and increase efficacy eg topiramate-phenterminePeripherally acting drugs (in development)Diuretics – salt in urineCNS drugs – side effects eg. reserpine and depressionCombinations to lower side effects and increase efficacyPeripherally acting drugs eg. angiotensin receptor blockers
82 Obesity Pharmacotherapy A Bad Safety Record 1893: Thyroid hormone -> hyperthyroidism1933: Dinitrophenol -> cataracts/neuropathy1937: Amphetamine -> addiction1967: Rainbow pills (digitalis & diuretics) -> CV sx1997: Fenfluramine -> valvulopathy2000: Phenylpropanolamine -> stroke2004: Herbal caffeine & ephedra -> CV sx2010: Sibutramine -> MI and stroke
83 Weight Loss Drugs Approved by FDA Generic Name Trade NamePhentermine/Topiramate QsymiaLorcaserin BelviqOrlistat Xenical, AlliPhentermine Adipex, Fastin, IonaminDiethylpropion Tenuate, Tenuate, DospanPhendimetrazine Bontril, Plegine, Prelu-2, X-TrozineMethamphetamine DesoxynBenzphetamine DidrexMazindol Sanorex, MazanorThis table lists the medications approved by the United States Food and Drug Administration (FDA) for the treatment of obesity; only sibutramine (Meridia) and orlistat (Xenical) have been approved for long-term use. All the approved medications act as anorexiants, with the exception of orlistat, which blocks the absorption of dietary fat. Anorexiants increase satiation (level of fullness, which regulates the amount of food consumed during a meal) or satiety (level of fullness after a meal, which determines frequency of eating), or both. Although approved by the FDA for short-term use, methamphetamine and benzphetamine are addictive and should be avoided. Three anorexiant medications have been removed from the marketplace because of increased risks of either valvular heart disease (fenfluramine and dexfenfluramine)  or hemorrhagic stroke (phenylpropanolamine)  associated with their use.References1. Khan MA et al. The prevalence of cardiac valvular insufficiency assessed by transthoracic echocardiography in obese patients treated with appetite-suppressant drugs. N Engl J Med. 1998;339:2. Kernan WN et al. Phenylpropanolamine and the risk of hemorrhagic stroke. N Engl J Med. 2000;343:
84 Efficacy of Currently Available Weight Loss Medications DrugPhentermineOrlistatLorcaserinPhentermine/TopiramateAverage Weight Loss3.6% > placebo2.75% > placebo3.3% > placebo9% > placebo
85 Phentermine Mechanism: Dose: 15-37.5 mg daily (AM) Appetite suppressantInhibits NE and dopamine releaseDose: mg daily (AM)FDA approved for short-term (3 months) useSide effects: Increased BP and HR, insomnia, agitation, dry mouth, headache, tremorEfficacy: More weight loss than placebo (~3-5%)
86 OrlistatMechanism: Inhibits lipases and blocks fat absorption by ~30% (reduction in absorbed fat)Dose: mg TID (with meals)FDA approved for long-term useSide effects: mild to moderate GI “events”, potential for malabsorption of fat soluble vitamins, liver toxicity?, nephrolithiasisEfficacy:More weight loss than placebo (~4%)More lose at least 5% (35-69% vs 16-30% with placebo)More lose at least 10% (16-25% vs 4-12% with placebo)Prevention of diabetes incidenceImprovements in glycemic control in T2D
88 BLOOM Study Body Weight Over Years 1 and 2 2.16 ± 0.14%5.81 ± 0.16%BLOOM = Behavioral Modification and Lorcaserin for Obesity.Smith SR, et al. N Engl J Med. 2010;363:
89 BLOOM Study Body Weight Over Years 1 and 2 2.16 ± 0.14%5.81 ± 0.16%BLOOM = Behavioral Modification and Lorcaserin for Obesity.Smith SR, et al. N Engl J Med. 2010;363:
90 BLOOM Study Body Weight Over Years 1 and 2 47.5%22.6%20.3%7.7%BLOOM = Behavioral Modification and Lorcaserin for Obesity.Smith SR, et al. N Engl J Med. 2010;363:
91 BLOOM-DM Change in Glycemic Parameters HbA1C, -0.5%Fasting Plasma GlucoseChange From Baseline (mg/dL)*Change From Baseline (%)†*****Study WeekStudy WeekPlaceboLorcaserin 10 mg twice a day*P <.001; †P <.05; least square mean change ± standard error of the mean. HbA1C = glycosylated hemoglobin.O’Neil PM, et al. Obesity. 2012;20:
92 Summary of Echocardiographic Safety Monitoring Confidential Draft - For Discussion Purposes OnlySummary of Echocardiographic Safety Monitoring4/13/2017More than 20,000 echocardiographsMore than 7,500 patientsLorcaserin did not increase the risk of valvulopathy above the pre-specified margin relative to placeboLorcaserin did not meaningfully affect regurgitant scores at any heart valveFDA defined valvulopathy relative risk: 1.16 (95% confidence interval (0.81, 1.67, NS)Taken together, data from more than 20,000 echoes in nearly 7500 patients show that lorcaserin did not increase the risk of valvulopathy above a pre-specified level, and did not meaningfully affect individual valve regurgitant scores. [PAUSE]Let’s move now to the evaluation of possible CNS effects…….
93 LorcaserinMost common AEs: Headache, nausea, dizziness, fatigue, dry mouth, constipationNotesDiscontinue if 5% weight loss is not achieved by week 12Discontinue for evaluation if signs or symptoms of valvular heart diseaseDEA Schedule CIVPregnancy category XInteresting effect on glycemia – greater benefit than expected for degree of weight lossBays HE. Expert Rev Cardiovasc Ther. 2009;7: ; Belviq [prescribing information]. Woodcliff Lake, NJ:Eisai; Inc
94 Phentermine and Fenfluramine Phen - Fen Weintraub M et al. Clin Pharmacol Ther. 51(5):586-94, 1992.
95 Phentermine/Topiramate ER Brand name: QsymiaApproved in 2012 for long-term weight managementMechanism:Phentermine: inhibits NE and dopamine releaseTopiramate: mechanism on weight loss is not knownIncreases satiety – appetite suppressantDosing:Start at 3.75/23mg daily x 2 weeks then↑to 7.5/46mgAfter 12 weeks can↑to 11.25/69mg and 15/92mg
96 Phentermine/Topiramate Phase III Trial Gadde KM et al. Lancet ;377(9774):
97 Phentermine/Topiramate Phase III Trial Gadde KM et al. Lancet ;377(9774):
98 Phentermine/Topiramate Phase III Trial Garvey, et al. Am J Clin Nutr 2012;95:
99 Phentermine/Topiramate ER Most common AEs: paresthesias, dizziness, dysgeusia, insomnia, constipation and dry mouth.Other AEs: BP and HR, headache, suicidal thoughts, myopia/secondary angle closure glaucoma, cognitive impairment, metabolic acidosis,↑creatinineNotesDiscontinue if 5% weight loss is not achieved by week 12DEA Schedule Class IVPregnancy category XSafety: fetal cleft palate - pregnancy test q mo.
100 Obesity Drugs and CVD Risk Factors Anti-Obesity AgentBPLDL-CTGHDL-CPhentermine/ Topirmate ERLorcaserinNo significant changeBays HE. Specialty Corner: Investigational Anti-obesity Agents to Treat Adiposopathy and "Sick Fat.” pagesCP Hayes, S AU
101 New Frontiers and Treatment Paradigms for Pharmacologic Management of Obesity What’s in the Pipeline?
102 Naltrexone/Bupropion Not yet FDA approvedCVD safety study in progressDose: 3 week escalation to 16/180mg SR bidMechanism:Naltrexone: opioid receptor antagonistBuproprion: NE/dopamine reuptake inhibitorAppetite suppressant, reduces cravings?Adverse events : Nausea, headache, constipation, dizziness, vomiting, insomnia, dry mouth & hot flushes
103 Bupropion 360 & Naltrexone 32 mg Placebo (N=511)NB16 (N=471)NB32 (N=471)PlaceboCompleters (N=290)NB16Completers (N=284)NB32Completers (N=296)ITT-LOCFObservedCompletersPlacebo-subtracted weight lossWeek 56NB16: -3.7%NB32: -4.8%Placebo-subtracted weight lossCompletersNB16: -4.9%NB32: -6.2%P<0.001 for NB16 and NB32 vs. Placebo at all time pointsGreenway FL et al. Lancet. 376(9741): , 2010
104 Liraglutide 3 mg/d in Obese Subjects Astrup A et al. Lancet 374(9701): , 2009
105 Zonisamide 360 + Bupropion 360 mg Weight Loss at 1 Year of Treatment Placebo (a)(N=72)Z120/B280(N=27)Z120/B360(N=36)Z240/B280(N=36)Z240/B360(N=26)Z360/B280(N=32)Z360/B360(N=39)(a) Placebo weight loss through 24 weeks as noted previously
106 Beloranib Methionine Aminopeptidase 2 (MetAP2) Inhibitor METAP2 is an enzyme which plays a key role in the production and use of fatty acidsReduced food intake?Reduced lipogenesis?Increased lipolysis?
107 Belornib - Body Weight in Mice Body weights during the course of 1 mg/kg/day fumagillin (ZGN-201) treatment
108 Belornib – Weight Loss in Humans Impact of ug/kg/dose ZGN-433 treatment on body weight in obese womenValues are medians ± SEM (n=6-8) for the per protocol population.*** p<0.001 by 2-way ANOVA and Bonferroni post-test.
109 SummaryObesity is a chronic physiologically controlled disease that requires chronic treatmentWe have two new CNS acting drugs for obesity lorcaserin and phentermine/topiramateThere are 3 drugs in late stage development: naltrexone/bupropion, liraglutide, and zonisamide/bupropionPeripherally acting drugs are being developed but may be limited by side effects.There is significant variability in the weight loss response, so important to consider predictors of response as we move forward
110 MARC-ANDRE CORNIER, MD - Program Chairman Investigations StratificationFront Line Clinical ApplicationsReal World Challenges inObesity ManagementCase Study-Based Learning Workshops and Clinical Simulations in Obesity ManagementMARC-ANDRE CORNIER, MD - Program ChairmanAssociate Professor of MedicineDivision of Endocrinology, Metabolism and DiabetesAnschutz Health and Wellness CenterUniversity of Colorado School of MedicineDenver, CO
111 Case Study 1ER, a 46-year-old woman, initially presents with high blood pressure, which has been well controlled with a diuretic agent.Since her last visit 6 months ago, she has been experiencing some heartburn, self-treated with over-the-counter H2-blockers, and more aching in her weight-bearing joints.On exam, her height is 66 inches and body weight is 190 pounds, up 5 pounds from her last visit. Blood pressure is 134/90, up several points from her last visit as well. The rest of the exam is unchanged.Her previous lab tests were within normal limits. Current test results indicate a fasting glucose of 118 mg/dL, total triglycerides of 255 mg/dL, and high-density lipoprotein (HDL cholesterol) of 42 mg/dL. All other tests are normal.
112 Case Study 1With a height of 66 inches and weight of 190 pounds, ER’s BMI is 31. This places her in Class I (mild) obesity.Her waist circumference is 36 inches. This, in addition to her triglycerides of 225 mg/dL, fasting glucose of 118 mg/dL, HDL cholesterol of 42 mg/dL, and blood pressure of 134/90, shows that she has the metabolic syndrome. This places her at increased risk of cardiovascular disease.In reviewing ER’s history, you identify five obesity-related conditions:HypertensionGastroesophageal reflux disease (GERD)Impaired glucose tolerance (possible diabetes)Hypertriglyceridemia and low HDL-C levelsArthralgia
113 Please Enter Your Response On Your Keypad Case Study 1 - Question 1You decide to order additional tests to evaluate ER’s hypertension and diabetes.Based on the NHLBI algorithm, treatment for ER’s obesity is indicated.At this point you would:Recommend diet and lifestyle changesInitiate orlistatInitiate lorcaserinInitiate phentermineInitiate phentermine HCl/topiramate CRPlease Enter Your Response On Your Keypad
114 Please Enter Your Response On Your Keypad Case Study 1 - Question 2In this case, diet and lifestyle changes were recommended, with an assessment after 90 days.The patient returned with an additional 2 lb. weight gain and reported difficulty in maintaining diet.At this point you would:Modify diet and lifestyle recommendations and reassess in 90 daysInitiate orlistatInitiate lorcaserinInitiate phentermineInitiate phentermine HCl/topiramate CRPlease Enter Your Response On Your Keypad
115 Please Enter Your Response On Your Keypad Case Study 1 - Question 390 days later, she is tolerating the weight management drug well, has experienced a 5% weight loss, and improvement in metabolic parameters. She reports increased energy and improved self-esteem.At this point you would:Cease pharmacotherapy and recommend diet and lifestyle changesCease pharmacotherapy, recommend diet and lifestyle changes, and revisit in 90 daysMaintain current pharmacotherapySwitch to alternative pharmacotherapyPlease Enter Your Response On Your Keypad
116 Case Study 1 - Question 490 days later, she is not tolerating the weight management drug well, has experienced a 5% weight loss, and improvement in metabolic parameters. She reports increased energy and improved self-esteem.At this point you would:Cease pharmacotherapy and recommend diet and lifestyle changesCease pharmacotherapy, recommend diet and lifestyle changes, and revisit in 90 daysMaintain current pharmacotherapySwitch to alternative pharmacotherapy
117 Case Study 2 42-year-old man with BMI 37 Weight 242 lbs., up 5 lbs. from 6 months earlierGout well-controlled on allopurinolHyperlipidemia (on low-dose simvastatin); bilateral knee arthritisExaminationCentral obesity with waist circumference 44 in.BP 132/82Laboratory studiesFasting glucose 90Fasting triglycerides 260Cholesterol 220; LDL cholesterol 146; HDL cholesterol 38Other tests normal
118 Case Study 2 Weight and lifestyle history Mildly heavy as a child “Grew out of it” during adolescence; participated in competitive sports in high school and collegeWeight stable at ~185 lbs. (BMI 28.3) until 12 years agoSlowly progressive 55 lb. weight gain over last 10 yearsWorks as salesman with hectic lifestyle; irregular meals; frequent fast foods and snackingNo previous serious weight loss attempts; feels healthyHas exercised at gym 4x/week over the past year with only 4 lb. weight loss
119 Please Enter Your Response On Your Keypad Case Study 2 - Question 1You increase the dose of simvastatin.What would you do to treat the obesity?Recommend a healthier and more regular dietEncourage a more vigorous exercise programRefer him to a psychologist for behavior modificationInitiate orlistat therapyInitiate lorcaserin therapy42 MBMI 37Central distributionPre-DMDyslipidemiaGERDGoutOAChildhood onsetSteady adult gainIrregular eaterFast food dietRegular exerciserHectic lifestylePlease Enter Your Response On Your Keypad
120 Case Study 2 Clinical progress He listens to your dietary advice and stops snackingHis hectic lifestyle continues, but he eats more meals at home and is able to change from fast food to family style restaurants when travelingContinues to exercise regularlyLost 4 lbs. (to 238 lbs.) in the first month but none since, despite maintaining his new lifestyleAt follow-up 3 months later, his weight is 239 lbs., BP 128/84 and LDL and total cholesterol in the normal range
121 Please Enter Your Response On Your Keypad Case Study 2 – Question 2What would you do now?Continue to encourage a healthy dietRefer to dietitian for nutritional managementRefer to a stress management programInitiate phentermine therapyInitiate lorcaserin therapyPlease Enter Your Response On Your Keypad
122 Case Study 2 Clinical progress He sees a dietitian who recommends a specific dietary regimen, which he follows reasonably wellOver the ensuing 3 months, he loses 12 lbs.At his annual visit 9 months after that, however, he has regained 10 of the 12 lbs. and weighs 237 lbs. (BMI 36.2)His cholesterol levels and BP remain normalHis fasting glucose is 114, and his triglyceride level is 222, and his HbA1c is 6.6%
123 Please Enter Your Response On Your Keypad Case Study 2 – Question 3What would you do now?Continue to encourage a healthy dietRefer back to the dietitian for additional counselingRefer to a stress management programInitiate phentermine therapyInitiate lorcaserin therapyPlease Enter Your Response On Your Keypad
124 Case Study 2 Clinical progress You begin phentermine at 15 mg/day, monitoring BP and pulse carefullyHe reports dry mouth that resolves after about 3 weeks; he otherwise tolerates the medication well, without tachycardia, hypertension or subjective adverse effectsAt 30 days, he has lost 5 lbs. (2.1% of pretreatment weight)At 3 months, he weighs 223 lbs. (BMI 34.1), having lost 14 lbs. (5.9%) on phentermineHe continues the recommended dietary changesTwo months later (on phentermine for 5 months), he has lost 1 additional lb. and weighs 222 lbs. (BMI 33.9)Total weight loss 20 lbs. since first visit; total weight loss on phentermine 15 lbs. (6.3%)
125 Please Enter Your Response On Your Keypad Case Study 2 - Question 4What would you do now?Continue the phentermine at 15 mg/day and re- emphasize the recommended diet and lifestyle changesStop the phentermine and follow his clinical progressStop the phentermine and start orlistat at 120 mg tidIncrease the phentermine to 30 mg/dayRecommend consultation for bariatric surgeryPlease Enter Your Response On Your Keypad
126 Case Study 2 Clinical progress He tolerates the increased dose of phentermine well with only transient dry mouthAt 30 days, he has lost 2 additional lbs. (0.8% of pretreatment weight)At 3 months, he weighs 221 lbs. (BMI 33.8), having lost 16 lbs. (5.9%) on phentermine overall
127 Please Enter Your Response On Your Keypad Case Study 2 - Question 5What would you do now?Continue the phentermine at 30 mg/day and refer back to the dietitianStop the phentermine and follow his clinical progressStop the phentermine and start orlistat at 120 mg tidAdd topiramate by substituting the low-dose combination of phentermine (3.75 mg/day) and topiramate (23 mg/day) for the phentermine aloneRecommend consultation for bariatric surgeryPlease Enter Your Response On Your Keypad
128 Case Study 2 Clinical progress He tolerates the low-dose phentermine-topiramate combination (“phen-top”) well, without adverse effectsAfter 14 days, you increase the phen-top dose to 7.5 mg phentermine + 46 mg topiramate dailyIn the first 30 days of phen-top therapy, he loses 3 lbs. to a weight of 218 lbs. (BMI 33.3)Over the next 3 months, he loses an additional 8 lbs. to a weight of 210 lbs. (BMI 32.1)
129 Case Study 2 Weight loss summary Initial weight 242 (BMI 37) Diet modification – 5 lb. weight loss over 1 year (2.1%)Phentermine – 16 lb. weight loss over 8 months (6.8%)Phentermine-topiramate combination – 11 lb. additional weight loss over 4 months (4.9%)Total medication-induced weight loss – 27 lbs. (11.4%)Current weight 210 lbs. (BMI 32.1), down 32 lbs. (13.2%) overall since initial visit 2 years earlier
130 Please Enter Your Response On Your Keypad Case Study 2 - Question 6What would you do now?Continue the phen-top at current dosingStop the phen-top, re-enforce lifestyle adjustments and follow his clinical progressIncrease the phen-top dosing to 15 mg phentermine + 92 mg topiramate daily (“high dose”)Add lorcaserin at 10 mg bidRecommend consultation for bariatric surgeryPlease Enter Your Response On Your Keypad
131 Case Study 3 51-year-old woman with BMI 43.3 Weight 252 lbs., height 5’4”Well-controlled hypertension, hypothyroidism, Barrett’s esophagus, osteoarthritis (s/p knee replacement), colonic polyps, and depressionType 2 diabetes on pioglitazone, glimepiride and insulin (long- and short-acting to total of 65 units/day)no eye, neurological or vascular complicationsSleep apnea well-controlled on CPAPOther medications include losartan, hydrochlorthiazide, omeprazole, levothyroxine, omeprazole, aspirin and sertraline
132 Case Study 3 Examination Central obesity with waist circumference 41 in.Benign, protuberant abdomen; no signs of chronic liver diseaseNo signs of peripheral neuropathyBenign abdomenLaboratory studiesFasting glucose 111HbA1c 7.1%AST 43, ALT 51, alkaline phosphatase 120BUN 32; creatinine 1.2TSH 5.64Other tests normal
133 Case Study 3 Weight and lifestyle history Normal weight as a child; overweight in college and graduate school (weight ; BMI 26-30)Progressive weight gain in adult life; “insatiable” appetite with frequent cravings and large portionsNumerous unsupervised, supervised and structured diets with variable weight loss (up to 30 lbs.); none maintainedAverage weight stable over the past few years; currently at highest lifetime weightMarried with grown children; works as financial plannerCooks regularly and well, and entertains oftenExercises three times a week with a physical trainer
134 Please Enter Your Response On Your Keypad Case Study 3 - Question 1You increase the dose of L-thyroxine.How would you initiate obesity treatment?Recommend a meal-replacement programSubstitute citalopram for sertralineRefer her to a psychologist for cognitive- behavior therapy for the depressionSubstitute metformin for glimepirideInitiate treatment with a combination of phentermine and topiramate51 FBMI 43.3Central distributionT2DM (55OSAHypothyroidismGERD / Barrett’sOAColonic polypsDepressionAdult onsetHealthy dietOften hungryLarge portionsRegular exerciserPlease Enter Your Response On Your Keypad
135 Case Study 3 Clinical progress You discontinue the sulfonylurea and start metformin at 500 mg bid, monitoring her glucose carefully and adjusting short-acting insulin as requiredIn the next 30 days, she loses 5 lbs. to a weight of 247 lbs. (BMI 42.4)You increase the metformin to 750 mg bidAt 3 months, she has lost a total of 14 lbs. (5.6%) to 238 lbs.She reports a noticeably diminished appetite and cravingsInsulin requirement falls from 65 to 52 units/day3 months later, her weight is stable at 235 lbs. (BMI 40.3), down 17 lbs. (6.7%)
136 Please Enter Your Response On Your Keypad Case Study 3 - Question 2What would you do now to treat the obesity?Refer to a commercial weight loss programSubstitute bupropion for sertralineInitiate therapy with a combination of phentermine and topiramateInitiate therapy with lorcaserinRefer for bariatric surgeryPlease Enter Your Response On Your Keypad
137 Case Study 3 Clinical progress Low-dose phen-top (phentermine 3.75 mg + topiramate 23 mg daily) initiated and well-toleratedAfter 14 days, you increase the phen-top dose to phentermine 7.5 mg + topiramate 46 mg daily with no adverse consequencesIn the first 30 days of therapy, she loses 4 lbs. (1.7%) to 231 lbs. (BMI 39.6)At 3 months, she has lost a total of 6 lbs. (2.6%) to 229 lbs.
138 Please Enter Your Response On Your Keypad Case Study 3 - Question 3What would you do now?Continue the phen-top at current dosing and add orlistat at 120 mg tidStop the phen-top and start phentermine at 15 mg dailyStop the phen-top and start lorcaserin at 10 mg bidStop the phen-top and start orlistat at 120 mg tidStop the phen-top and substitute liraglutide s.c. for the pioglitazonePlease Enter Your Response On Your Keypad
139 Case Study 3 Clinical progress She tolerates the new medication well After 30 days, she reports feeling increased hunger and her weight has increased 3 lbs. to 232 lbs.After 60 days, her weight remains at 232 lbs. (BMI 39.8)Her diabetes remains well-controlled with a fasting glucose of 114 and HbA1c of 6.9%
140 Please Enter Your Response On Your Keypad Case Study 3 - Question 4What would you do now?Stop all weight loss medications and refer to a dietitian to reinforce healthy eating habitsStop all weight loss medications and refer to a psychologist for behavioral therapyContinue the current regimen and restart a combination of phentermine and topiramateStop all weight loss medications and institute an 8-week physician-supervised very low calorie diet (VLCD)Stop all weight loss medications and refer for bariatric surgeryPlease Enter Your Response On Your Keypad
141 Case Study 3 Clinical progress She undergoes uneventful laparoscopic Roux-en-Y gastric bypass with post-operative weight loss ~50 lbs.Her diabetes remains well controlled (HbA1c 6.6%) without need for insulin, pioglitazone or liraglutide, and on a reduced dose of metformin (500 mg bid)Other comorbidities improved or resolved except for continued joint pain and reflux symptomsOne year after surgery, her weight is down 51 lbs. to 181 lbs. (BMI 31.1), which has been stable for more than 3 monthsShe feels much better overall but is a bit disappointed in the weight loss outcome (which is less than the average 65% excess weight loss from this operation)
142 Please Enter Your Response On Your Keypad Case Study 3 - Question 5What would you do now?Indicate that there is no further therapy beyond surgery and reinforce the need to follow a healthy lifestyleRefer her to a psychologist to help address her expectationsEncourage her to extend post-operative weight loss with a low-calorie (calorie restricted) dietInstitute pharmacological therapy with lorcaserinRefer her back to the surgeon for consideration of revising the surgical procedurePlease Enter Your Response On Your Keypad
143 Case Study 3 Clinical progress Lorcaserin at 10 mg/day is started and well-toleratedOver the next 6 months, she loses an additional 15 lbs. to a weight of 164 lbs. (BMI 27.3)Her comorbidities remain improved, and her diabetes is in remission off all medications (HbA1c 6.3%)
144 Case Study 3 Weight loss summary Initial weight 252 (BMI 43.3) Substitution for weight-promoting drugs – 23 lb. weight loss over 1 year (2.1%)Phentermine-topiramate combination – 16 lb. weight loss over 3 months (2.6%)Other pharmacological agents – 3 lb. weight gain over 2 months (1.3%)Total medical weight loss – 20 lbs. (7.9%)Gastric bypass – 51 lbs. (22.0%) weight loss over 1 year (58.8% excess weight loss)Lorcaserin after surgery – 15 lbs. over 6 monthsCurrent weight 159 lbs. (BMI 27.3), down 93 lbs. (36.9%) since initial visit 3 years earlier
145 Case Study 4 46-year-old woman with BMI 30.7 Weight 190 lbs., up 5 lbs. from 6 months earlierHypertension, heartburn, weight-bearing joint painExaminationCentral obesity with waist circumference 36 in.BP 134/90Laboratory studiesGlucose 118; HbA1c 6.4%Triglycerides 255 mg/dL, LDL cholesterol 140HDL cholesterol 42 mg/dLOther tests normal
146 Case Study 4 Weight and lifestyle history Normal weight as child Progressive weight gain after college exacerbated after having children in late 20sPreviously on intermittent diets with up to 20 lb. weight loss, but invariable weight regainEats mostly home-prepared foodLittle or no snacking, but eats meals irregularlySingle mother of 2 teenagers, with steady boyfriendWorks as nursing assistant on evening and night shiftWalks extensively at work; no structured exercise
147 Please Enter Your Response On Your Keypad Case Study 4 - Question 1What treatment would you initially recommend for this patient?1. Broad-based diet and lifestyle counseling2. Implementation of moderate structured exercise regimen3. Cooking classes4. Change jobs5. Initiate pharmacotherapy for obesity46 FBMI 30.7Central distributionPre-DMHTNDyslipidemiaGERDJoint painObesity onset 20sFailed dietsHome-cookerIrregular eaterWalks a lotNight shift workerStressful lifePlease Enter Your Response On Your Keypad
148 Case Study 4 Clinical progress Modest, regular, aerobic exercise program initiated and maintainedAt follow-up 2 months later, her weight was down 6 lbs. to 184 lbs. (BMI 29.7)
149 Please Enter Your Response On Your Keypad Case Study 4 – Question 2You recommend that she continue the exercise program.What else would you recommend now?Laud her success and encourage continuing a healthy lifestyleRefer to exercise trainer to help with exerciseEncourage a more regular eating patternSuggest that she change to day shiftInitiate pharmacotherapy for obesityPlease Enter Your Response On Your Keypad
150 Case Study 4 Clinical progress Continued regular exercise program Stopped grazing and began eating on regular scheduleChange in eating schedule resulted in stabilization of sleep patterns as wellAt follow-up three months later, her weight was down 8 more lbs. (14 lbs. weight loss total ), to 176 lbs. (BMI 28.4)She describes increased energy and improved self-esteem
151 Please Enter Your Response On Your Keypad Case Study 4 – Question 3What would you recommend now?Encourage a healthy diet and reassess HbA1cRefer to dietitian for nutritional managementInitiate pharmacotherapy for obesityRecommend bariatric surgical evaluation for type 2 diabetesRefer to plastic surgeon for liposuctionPlease Enter Your Response On Your Keypad
152 Investigations Stratification Front Line Clinical ApplicationsSummary and Vision Statement Near Term Challenges and Potential Strategies for Optimizing Obesity Management in the Primary Care Setting
153 SummaryObesity is a chronic physiologically controlled disease that requires chronic treatmentMust be approached like other chronic diseasesYes, there are still many barriers and challenges to overcome with the management of obesityBut there are also many opportunitiesAwareness and education are critical!Lifestyle modification is at the core of all our therapeutic optionsWe have good pharmacotherapies and new agents on the horizon yet these are underusedWe must use all of the tools at our disposition
154 Summary Reasons Why You Should Treat Overweight-Obesity Excess adiposity adversely impacts healthObesity is a medical condition with a physiologic and behavioral component like many other chronic medical conditions we routinely treat on an ongoing basis in primary careOur patients are asking for helpIf you don’t, then who will?
155 Questions and Answers Investigations Stratification Front Line Clinical ApplicationsQuestions and Answers
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