WST18 PCU Track 2 Session 1 pmiCME Obesity

7:45 – 9:00 AM

Tightening the Belt: A Coordinated & Shared-Decision Approach to the Management of Obesity

SPEAKERSW. Timothy Garvey, MDRobert F. Kushner, MD, FACP

Presenter Disclosure Information

► W. Timothy Garvey, MD: Advisory Board for Merck; Novo Nordisk Inc.; Janssen.Research: Pfzer; Merck; Sanofi; Novo Nordisk Inc.

► Robert F. Kushner, MD, FACP: Advisory Board for Novo Nordisk Inc.; Retrofit; and Weight Watchers.

The following relationships exist related to this presentation:

Off-Label/Investigational Discussion► In accordance with pmiCME policy, faculty have been asked to disclose discussion of unlabeled or

unapproved use(s) of drugs or devices during the course of their presentations.

Learning Objectives

Utilize guideline-recommended strategies to screen for and diagnose individuals with obesity to minimize complications1

Identify individuals with obesity who are candidates for pharmacologic treatment based on patient characteristics, preferences, and expectations

2

Utilize pharmacologic agents as adjunct therapy to intensive lifestyle/behavioral modification in individuals who are obese based on guidelines and available efficacy/safety data

3

Important Concept=

OVERVIEW OF OBESITY

Adult Obesity Rates

State of Obesity 2016. http://stateofobesity.org/states

1990 2016

Obesity is a Disease | AMA Criteria

Mechanick JI, et al. Endocr Pract. 2012;18:642-648.

Impairment of Normal Function

Impairment of Normal Function

• Physical impairments

• Altered physiologic function (inflammation, insulin resistance, dyslipidemia, etc.)

• Altered regulation of satiety in the hypothalamus

• Physical impairments

• Altered physiologic function (inflammation, insulin resistance, dyslipidemia, etc.)

• Altered regulation of satiety in the hypothalamus

Characteristic Signs/Symptoms

Characteristic Signs/Symptoms

• Increased body fat mass

• Joint pain• Impaired mobility• Low self-esteem• Sleep apnea

• Increased body fat mass

• Joint pain• Impaired mobility• Low self-esteem• Sleep apnea

Harm or MorbidityHarm or

Morbidity• CVD• T2DM• Metabolic syndrome• Cancer• Death• Altered metabolism

• CVD• T2DM• Metabolic syndrome• Cancer• Death• Altered metabolism

Regulation of Energy Intake

Apovian CM, Aronne LJ, Bessesen D et al. J Clin Endocrinol Metab. 2015;100:342-362.

Causes of Obesity

Bray GA, et al. Lancet. 2016;387:1947-1956.

OBESITYOBESITY

EpigeneticEpigenetic

GeneticGenetic

PhysiologicPhysiologic

BehavioralBehavioral

SocioculturalSociocultural

EnvironmentalEnvironmental

Drugs That Cause Weight Gain

(1) Kushner RF, Ryan DH. JAMA. 2014;312:943-952. (2) Apovian CM, et al. J Clin Endocrinol Metab. 2015;100:342-362.

Category Drugs That May Cause Weight Gain Possible Alternatives

Neuroleptics Thioridazine, haloperidol, olanzapine, quetiapine, risperidone, clozapine Ziprasidone, aripiprazole

Antidiabetic agents Insulin, sulfonylureas, thiazolidinediones AGIs, DPP-4i’s, SGLT2i’s, GLP-1 RAs, metformin

Steroid hormones Contraceptives, glucocorticoids, progestational steroids Barrier methods, NSAIDs

Tricyclic antidepressants Amitriptyline, nortriptyline, imipramine, doxepin Protriptyline, bupropion, nefazodoneMAOIs PhenelzineSSRIs Paroxetine Fluoxetine, sertralineOther antidepressants Mirtazapine, duloxetine Bupropion

Anticonvulsants Valproate, carbamazepine, gabapentin, pregabalin, vigabatrin

Topiramate, lamotrigine, zonisamide, felbamate

Antihistamines Cyproheptadine Inhalers, decongestantsβ- and α-blockers Propranolol, doxazosin ACEIs, CCBs

Complications of Obesity

(1) Daniel S, et al. Curr Opin Endocrinol Diabetes Obes. 2013 Oct;20(5):377-88. (2) Pi-Sunyer X. Postgrad Med. 2009 Nov;121(6):21-33.

ObesityObesity

Sleep apnea Osteoarthritis Stress incontinence GERD Dismobility/disability

Sleep apnea Osteoarthritis Stress incontinence GERD Dismobility/disability

CVDCVD

Prediabetic StatesPrediabetic States

HypertensionHypertensionDyslipidemiaDyslipidemia

DiabetesDiabetes

Depression Gallbladder

Disease Cancer

Depression Gallbladder

Disease Cancer

Cardiometabolic Disease

Biomechanical Complications

Other Complications

NAFLDNAFLD PCOSPCOS

PCOS: Polycystic ovary syndrome; NAFLD: Non-alcoholic fatty liver disease

BR6

ASSESSMENT & DIAGNOSIS

BR6 mechanical and physiologicalBoris Rozenfeld, 4/26/2018

Assessment for Obesity

OGTT, oral glucose tolerance test; TG, triglycerides

Waist circumferenceWaist circumference► Fasting blood glucose► Lipid parameters

TG, HDL-C, LDL-C► HbA1c

► Full medical history► BMI and weight history

History & Physical ExamHistory & Physical Exam Blood pressureBlood pressure

Laboratory valuesLaboratory values

CaseRicardo: 53-year-old Male

Chief Complaint“I am tired and feel sleepy during the day”

History of Present IllnessRicardo, a 53-year-old male who comes in for an initial appointment as he just moved from out of state. ► Over past 2 years he has had disruptive sleep, morning

headaches, and increased daytime sleepiness.►His wife tells him that he snores.

BR2


Past Medical HistoryHypertension × 5 yrsDyslipidemia × 6 yrsNephrolithiasis (calcium oxalate)

MedicationsLosartan/HCTZ 100 mg/25 mg once daily Atorvastatin 40 mg once dailyAspirin 81 mg once daily

Family HistoryFather: T2DM, dyslipidemia, CAD, rheumatoid arthritisMother: Alzheimer’s disease, HTN, depression


Social History► Bank loan officer► Lives at home with his wife and two children► Exercise Minimal – occasionally takes a 20-min walk after

dinner Mostly sits during work

► Diet Most meals are home cooked with a lot of fried food

and carbohydrates► Tobacco: 20 pack years (quit 3 years ago)► EtOH & illicit substances: Denies

BR2 Tease out depression through historyBoris Rozenfeld, 4/26/2018


Review of Systems►Endocrine: Libido decline

in the last year►Respiratory: Reports

snoring►Gastrointestinal:

Occasional heartburn►Psychiatric: reduced mood►Musculoskeletal:

Occasional pain in right knee

Physical ExamHeight - 69 in (178 cm)Weight - 267 lbs. (104 kg)BMI - 39.7 kg/m2

BP- 144/82 mm Hg


Laboratory Evaluation

Fasting blood glucose (FBG) = 106 mg/dLHbA1c = 6.4%Total-C = 182 mg/dLHDL-C = 38 mg/dLLDL-C = 98 mg/dLTriglycerides = 160 mg/dLeGFR = ≥ 90 mL/min/1.73 m2

LET’S CHAT WITH RICARDO

BR17 Obesity-Focused History

►Recap of patient life events that coincided with weight gain Smoking cessation Medication initiation Pregnancy or menopause Job loss Change in marital status

Life Events & Weight Gain Diet & Activity

*AACE Obesity focused Review of Systems http://obesity.aace.com/files/obesity/toolkit/obesity_focused_review_of_systems_patient_form_reader_version.pdf

►Extent of daily physical activity►Sleep habits and difficulties►Food preferences and

frequency/quantity of meals►Psychological assessment Mood/anxiety disorders, ADD, PTSD Eating disorders

BR17 How have you been treated? Response to Tx?Have you felt stigmatized? etc? How has the healthcare system responded (shaming, etc)?

Life-trajectory weightBoris Rozenfeld, 4/27/2018

Obesity-Focused History

Review of Systems

Weight Loss Readiness

► Checklist of obesity-related complications*

*AACE Obesity focused Review of Systems http://obesity.aace.com/files/obesity/toolkit/obesity_focused_review_of_systems_patient_form_reader_version.pdf

► Motivation and social support► Psychiatric status► Presence of stressful life

circumstances

► Time constraints► Goals and expectations

Lifestyle Events–Body Weight Graph

Ogden J, et al. Psychol Health Med. 2009;14:239 –249.

A graph of the coincidence of weight gain with life events can be a useful tool to help identify clinical, behavioral, and psychosocial determinants of obesityA graph of the coincidence of weight gain with life events can be a useful tool to help identify clinical, behavioral, and psychosocial determinants of obesity

Time

Wei

ght

Commercial weight loss program

Smoking cessation

Longer commute

Children

First jobCollege

Obesity Management Guidelines Diagnosis & Assessment of Obesity

Garvey WT, et al. Endocr Pract. 2016 Jul;22 Suppl 3:1-203.

ScreeningScreening Annual BMIAnnual BMI

►BMI ≥ 25 kg/m2

►BMI ≥ 23 kg/m2

for some ethnicities

►BMI < 25 kg/m2

►BMI < 23 kg/m2

for some ethnicities

DiagnosisDiagnosis

1. Clinical interpretation of BMI2. Waist circumference if BMI

< 35 kg/m2

Clinical Component of Diagnosis

Clinical Component of Diagnosis

BR20

BR20 insert a slide with all guidelinesBoris Rozenfeld, 4/27/2018

Waist Circumference

http://www.nhlbi.nih.gov/guidelines/obesity/prctgd_c.pdf. Accessed April 18, 2018.

1) Locate upper hip bone and top of right iliac crest

2) Place measuring tape around abdomen at level of iliac crest, keeping it parallel to the floor

3) Ensure tape is snug but not compressing the skin

Only necessary for BMI < 35 kg/m2

Abnormal: ♀ ≥ 40in ♂ ≥ 35in

Classification of Obesity by BMI and Waist Circumference

World Health Organization.

ClassificationBMI Waist

BMI (kg/m2)

Comorbidity Risk

Waist Circumference and Comorbidity RiskMen ≤40 in (102 cm)Women ≤35 in (88 cm)

Men >40 in (102 cm)Women >35 in (88 cm)

Underweight <18.5Low but

other problems

Normal Weight 18.5-24.9 Average

Overweight 25-29.9 Increased Increased HighOverweight class I 30-34.9 Moderate High Very highOverweight class II 35-39.9 Severe Very high Very highOverweight class III ≥40 Very severe Extremely high Extremely high

RicardoRicardo

Medical Diagnosis of Obesity


Anthropometric Component

Candidates for Weight Loss Therapy

Patients Present with Weight-related Disease of Complication

(Clinical Component)

Patients Present with

BMI ≥ 25 kg/m2

or BMI ≥ 23 kg/m2

in certain ethnicities, and

excess adiposity

Evaluate for weight-related complications

Evaluate for overweight or obesity

Prediabetes PCOSMetabolic syndrome Female infertilityT2DM Male hypogonadism

Dyslipidemia Obstructive sleep apnea

Hypertension Asthma/reactive airway disease

CVD Osteoarthritis

NFLD Urinary stress incontinence

GERD Depression

TREATMENT OF OBESITY

Treatment Goals | Patient Perspective

ASK THE PATIENTWhat are your goals?

ASK THE PATIENTWhat are your goals?

Patients often want to lose ~30% of body weight

A weight loss of “only” 7-10% may be deemed as “failure” by patients

Patients often want to lose ~30% of body weight

A weight loss of “only” 7-10% may be deemed as “failure” by patients

Treatment Goals | Patient Perspective

►Advise patients to accept steady incremental progress; goal is improved health — not necessarily reduced weight

►Initial weight loss goal (for most patients): 5% to 10% loss at 6 months Increase in muscle mass may be more important than decrease in

fat mass►Long-term goal (if desired): additional energy deficit

recalculated for the next weight loss goal

Lifestyle Therapy


Intensification of Lifestyle Therapy


Simple advice to lose weight in doctor’s office

Simple advice to lose weight in doctor’s office

Internet programs or self-help booksInternet programs or self-help books

Advice from dietitian

Advice from dietitian

Structured programs

(Weight Watchers, YMCA, telecommunication)

Structured programs

(Weight Watchers, YMCA, telecommunication)

Multidisciplinary structured programs

Multidisciplinary structured programs

Physician-driven individualized

structured programs

Physician-driven individualized

structured programs

Weight Loss Diets

Diet/Program Description

Weight Watchers Point system based encourages healthy choices

Jenny Craig Prepackaged meals, lifestyle/behavior support, consultants

Volumetrics Focus on low-density, high-volume foods

Health Management Resources Meal replacements, fruits/vegetables; physical exercise

Biggest Loser Regular meals (fruits, vegetables, lean protein, whole grains), portion control, food journal, exercise

Flexitarian Mostly vegetarian

Raw food Raw foods (fresh fruits, berries, vegetables, nuts, seeds, herbs)

Slim-Fast Meal replacement program

Vegan diet Excludes all animal products


Ricardo was initially hesitant to start medications for weight loss. Instead, he was optimistic about giving a rigorous diet and exercise program a try. You also refer him and his wife to a dietician in order to make changes to their diet.

After 3 months, Ricardo lost 5 lbs. (2% of initial body weight). He realizes that he is not at goal and would like to continue with lifestyle modification for another 3 months.

Ricardo returns 3 months later and has lost an additional 3 lbs., putting him at 3.5% of initial body weight. He reports that it’s difficult for him to exercise more regularly due to pain in his right knee.

BR23BR25

Agents for Short-term Weight Management

Benzphetamine PhentermineDiethylpropion Phendimetrazine

ConsiderationsADVERSE EFFECTS: Increase in HR, BP, insomnia, dry mouth, constipation, nervousnessAVOID: Heart disease, poorly controlled HTN, pulmonary HTN, or h/o addiction or drug abuse.CONTRAINDICATIONS: h/o CVD, hyperthyroidism, glaucoma, MAOI therapy, agitated states, pregnancy, or breast feeding

Limit to short-term use (≤ 12 weeks)

BR22 Agents for Long-term Weight Management

Medication Mechanism of Action Year Approved

Orlistat (Xenical™; Alli™- OTC) Lipase inhibitor 1999

Lorcaserin (Belviq®) Serotonin (5HT2c) receptor agonist 2012

Phentermine/Topiramate ER(Qsymia®)

NE-releasing agent (phentermine)

GABA receptor modulation (topiramate)2012

Naltrexone ER/ Bupropion ER(Contrave®)

Opiate antagonism (naltrexone)Reuptake inhibitor of DA and NE (bupropion) 2014

Liraglutide 3.0 mg(Saxenda®)

GLP-1 receptor agonist 2014

BR23 Conversation w/Richard: What was hard about adhering to the plan? Do you think you'd like to take something to decrease apetite?Boris Rozenfeld, 4/27/2018

BR25 Transition to TimBoris Rozenfeld, 4/27/2018

Slide 41

BR22 Add phentermineBoris Rozenfeld, 4/27/2018

Regulation of Energy Intake

Apovian CM, Aronne LJ, Bessesen D et al. J Clin Endocrinol Metab. 2015;100:342-362.

Rationale for Using Pharmacotherapy

Pharmacotherapy may… Increase motivation Improve adherence to dietary intervention Improve chances of achieving target

weight loss Help maintain long-term weight loss

When to Initiate Weight Loss Medications


NO COMPLICATIONSOverweight or obesity with no clinically significant weight-related complications (secondary prevention)

NO COMPLICATIONSOverweight or obesity with no clinically significant weight-related complications (secondary prevention)

MILD TO MODERATE COMPLICATIONSMild-moderate weight-related complications when lifestyle therapy is anticipated to achieve sufficient weight loss to ameliorate the complication (tertiary prevention)

MILD TO MODERATE COMPLICATIONSMild-moderate weight-related complications when lifestyle therapy is anticipated to achieve sufficient weight loss to ameliorate the complication (tertiary prevention)

Initiate Lifestyle Therapy if…

Initiate Weight Loss Medication as an Adjunct to Lifestyle Therapy if…

FAILURE ON LIFESTYLE THERAPYProgressive weight gain or failure to achieve clinical improvement in weight-related complications on lifestyle therapy alone

FAILURE ON LIFESTYLE THERAPYProgressive weight gain or failure to achieve clinical improvement in weight-related complications on lifestyle therapy aloneWEIGHT REGAIN ON LIFESTYLE THERAPYOverweight (BMI 27-29 kg/m2) or obesity with weight regain following initial success on lifestyle therapy alone

WEIGHT REGAIN ON LIFESTYLE THERAPYOverweight (BMI 27-29 kg/m2) or obesity with weight regain following initial success on lifestyle therapy alonePRESENCE OF WEIGHT-RELATED COMPLICATIONSOverweight (BMI 27-29 kg/m2) or obesity with weight-related complications, particularly if severe

PRESENCE OF WEIGHT-RELATED COMPLICATIONSOverweight (BMI 27-29 kg/m2) or obesity with weight-related complications, particularly if severe

LET’S CHAT WITH RICARDO

Efficacy of Approved Medications


Baseline body weight of ≈ 100 kg and average BMIs in the range of 35-39.9 kg/m2

-7.9 -5.8 -7.8 -6.1 -8.0-4.1 -2.8 -1.2 -1.3 -2.6

-15

-10

-5

0

Δ B

ody

Wei

ght

(%)

Intention to Treat Population

-8.8 -7.9 -9.6 -8.1 -9.2-4.3 -4.0 -1.6 -1.8 -3.5

-15

-10

-5

0

Δ B

ody

Wei

ght

(%)

Completer Population

Liraglutide 3.0 mg/dOrlistat 360 mg/dNaltrexone/bupropion 32/360 mg/d

Phentermine/topiramate 7.5/46 mg/dLorcaserin BID 20 mg/dControl

Efficacy vs. Adverse Events

Khera R, et al. JAMA. 2016;315:2424-2434

Probability of having the

fewest number of adverse

events

Probability of being highest ranked in achieving ≥ 5% weight loss

1.0

0.8

0.6

0.4

0.2

00 0.2 0.4 0.6 0.8 1.0

Placebo

LorcaserinOrlistat

Naltrexone/bupropion

Liraglutide 3.0 mg

Phentermine/topiramate

Weight Loss Agents | Patient Preferences

Doyle S, et al. Obesity. 2012;20:2019-2026.

Degree of anticipated weight loss Impact on long-term health risk Delivery mode Adverse effects Lifestyle management efforts Cost

Individualization of Therapy


Consideration Orlistat Lorcaserin Phentermine/ Topiramate

Naltrexone ER/ Bupropion ER

Liraglutide 3.0 mg

Prevent T2DM Insufficient data Insufficient data

T2DMSevere renal impairment

(eGFR < 30 mL/min)

Oxalate nephropathy Urinary clearance of drug or metabolite

Avoid vomiting &

volumedepletion

NephrolithiasisCalcium oxalate stones

Calcium phosphate

stones

DepressionInsufficient data

Avoid max dose (15 mg/92 mg

QD)

Insufficient dataAvoid

serotonergicdrugs

Avoid in adolescents/young adults

Preferred AvoidUse with caution

Individualization of Therapy Consideration Orlistat Lorcaserin Phentermine/

TopiramateNaltrexone ER/ Bupropion ER

Liraglutide 3.0 mg

Psychoses Insufficientdata Insufficient data Insufficient data

GlaucomaContraindicated; may trigger angle

closure

May trigger angle closure

Seizure 15/92 mg—taper slowly to stop

Bupropion lowers seizure threshold

Pancreatitis MonitorMonitor

Cases with history

Opioid use Will antagonizeopioids/opiates

Age ≥ 65 years Limited data Insufficient data Limited data Insufficient data Limited data

Alcoholism/addiction Abuse potential (high dose)?

Insufficient data;(TOP benefit?) Seizure risk

Individualization of Therapy for CVD


Preferred AvoidUse with caution

Consideration Orlistat Lorcaserin Phentermine/ Topiramate

Naltrexone ER/ Bupropion ER

Liraglutide 3.0 mg

CAD HR HR, BP HR

Arrhythmia for bradycardia

HR, rhythm

HR, rhythm, BP HR, rhythm

CHF Insufficient data

Hypertension HR HR, BP

HRContraindicationUncontrolled

HTN


► Ricardo is initiated on liraglutide at 0.6 mg SC daily to be titrated up weekly with 0.6 mg intervals to 3.0 mg.

► After 2 weeks of liraglutide (1.2 mg at this time), Ricardo reports nausea and occasional vomiting.

Treatment Monitoring and Adjustment

Apovian CM, et al. J Clin Endocrinol Metab. 2015;100:342-362

InitiateInitiate • Initiate therapy with dose escalation• Do not exceed the highest approved dose

MonitorMonitor• Monitor for efficacy, safety, and tolerability

• First 3 months: Once a month• After 3 months: Every 3 months

AdjustAdjust• If effective* Continue• If ineffective discontinue

• Consider alternative medications, treatments• Discontinue if there are safety or

tolerability issues*Weight loss ≥ 5% at 3 months


► Ricardo takes note of your suggestions and starts taking liraglutide within 60 minutes before morning and evening meals and avoids taking it close to a large or high fat meal.

► After a 3-month follow-up, Ricardo has lost an additional 12 lbs., which is 5.4% of his previous weight.

► His energy level has increased and he reports that his mood improved

► You and Ricardo are both very happy with the progress he’s made so far and will continue with the same regimen.

Summary

► All adult patients be screened for overweight and obesity BMI WC: If BMI < 35 kg/m2

o Abnormal WC: ♀ ≥ 40in ♂ ≥ 35in

► Initiation of drug therapy should be individualized► Choice of medication depends on complications, side effect profile of

medications, warnings and cautions, and other aspects of medical history in an individual patient

► Candidates for drug therapy BMI ≥ 30 kg/m2

BMI of 27-29.9 kg/m2 with complications

WST18 PCU Track 2 Session 1 pmiCME Obesity

Documents

Transcript of WST18 PCU Track 2 Session 1 pmiCME Obesity