Obesity Management in Primary Care - American College of ......Obesity Management in Primary Care Scott Kahan, MD, MPH Director, National Center for Weight and Wellness ... B. Obesity

Obesity Management in Primary Care

Scott Kahan, MD, MPH

Director, National Center for Weight and Wellness

Medical Director, Strategies to Overcome and Prevent (STOP) Obesity Alliance

Faculty, Johns Hopkins Bloomberg School of Public Health

[email protected]

Which of these best characterizes your

beliefs about obesity treatment?

A. Obesity is a medical condition; it is the healthcare provider’s responsibility to ensure that patients are counseled and receive treatment for obesity

B. Obesity is a personal issue; it is the patient’s responsibility to ensure that he/she gets the help they need

C. Obesity is both a medical and personal issue; the responsibility for addressing obesity is shared between healthcare providers and patients

D. Obesity is an issue of personal responsibility and willpower; patients should take better care of themselves and not burden the healthcare system

An Obesity Paradox

Petrin C, Kahan S, et al. Obes Res Clin Pract, 2016.

When HCPs Talk to Patients About Weight…

• 6-8x increased likelihood of correctly perceiving excess weight status

• 2-3x increased likelihood of having obesity management plan in place

• 3-4x increased likelihood of attempting weight loss

• 2x increased likelihood of losing >5% body weight

• Improved weight loss, weight loss maintenance, weight-related behaviors, weight-related comorbidities

Kahan, Petrin 2017 (submitted); Post 2011; Jackson 2013; Rose 2013; Bardia 2007; Pool 2014; McTigue 2003; Moyer 2012; Digenio 2009.

An Obesity Paradox

Current Practice: (Under-whelming)

• Under-diagnosis – BMI 30-35: 10.2% diagnosed

– BMI >50: 56.8%

• Under-documentation – 34% of 33,718 patients with severe obesity

• Under-discussion– 54% with BMI >25 told of excess weight

– 2% of PCPs discussed recorded BMI with patients

• Under-counseling– 67% with severe obesity receive weight loss advice

– Weight discussions last as little as 55 seconds

Kahan S, Petrin C 2017 (submitted); Crawford 2010; Hatoum 2015; Post 2011; Antognoli 2014; Wilkinson 2014; Eaton 2002.

% o

f el

igib

le p

ati

ents

Samaranayake NR, et al. Ann Epidemiol 2012;22:349-53. Zhang S, et al. Obes Science Pract. 2016;2:104-114. Ponce J, et al. SOARD 2016;12:1637. Thomas CE et al. Obesity. 2016;24:1955-1961.

Current Practice: Under-Treatment

Today

• Obesity epidemiology and background

• Why is it so hard to lose/maintain weight?

• Key clinical guidelines for obesity management

• Evidence-based treatment options for obesity

Prevalence of Obesity in US Adults%

Pre

vale

nce

40

30

20

0

BMI >30

10 BMI >40

Fryar CD et al. NCHS Health E-stat. September 2014. Ogden CL, et al. NCHS Data Brief 219. Nov 2015. CDC/NCHS, NHANES 2007-2010.

MenWomen

Yuen M, Kahan S, et al, 2016.

Obesity Comorbid Conditions

320,000 Deaths/Year Attributable to Obesity

Grover SA, et al. Lancet Diab Endocrinol. 2015;3(2):114-122.www.milkeninstitute.org/publications/view/833.

Obesity Strongly Impairs Quality of Life

Sturm R. Health Affairs. 2002;21(2):245-53.

Why Is It So Hard To Manage Weight?

www.gov.uk/government/uploads/system/uploads/obesity-map-full-hi-res.pdfKahan S, et al. Johns Hopkins U Press, 2014.

Effect of Weight Loss on Satiety

Kissileff HR, et al. Am J Clin Nutr, 2012.

Before Meal After Meal

Insulin Amylin

Leptin PYY

CCK GLP-1

Ghrelin

10

0

0 8 18 26 36 44 52 62

Weeks

209

198

187

176

Wei

ght

Hormone Changes and Hunger Persistently Oppose Weight Loss

40

20

0

0 30 60 120 180 240

Hu

nge

r/D

rive

to

Eat

Week 0 Week 10 Week 62

Sumithran P et al. N Engl J Med. 2011;365:1597‒1604.

Effect of Weight Loss on EE

Lam YY, Ravussin E. Eur J Clin Nutr 2017;71(3):318-22. Lam YY, Ravussin E. Mol Metab 2016;5(11):1057-71.Goldsmith R, et al. Am J Physiol, 2010.

CDC Framework for Addressing Obesity

Key Obesity Guidelines

AHA/ACC/TOS Guidelines for Managing Overweight and Obesity in Adults

Pharmacologic Management of Obesity: An Endocrine Society Clinical Practice Guideline

AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults. Circulation, 2013.Pharmacological Management of Obesity: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab, 2015.

“Modest, sustained weight loss of 3-5% produce clinically meaningful health

benefits, and greater weight loss produces greater benefits”

AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults. Circulation, 2013.Knowler, et al. NEJM. 2002;346:393–403.

Behavioral Therapy (1079)

Metformin(1073)

Placebo

(1082)

Adults with Obesity and Pre-Diabetes (n=3234)

Knowler, et al. NEJM. 2002;346:393–403.

-8

0 1.0 2.0 3.0 4.0

Time (years)

-6

-4

-2

0

% W

eigh

t Lo

ss

0 1.0 2.0 3.0 4.00

10

20

30

40

Time (years)

Cu

mu

lati

ve in

cid

en

ce T

2D

(%

)

Lifestyle intervention

Metformin

Placebo

Modest Weight Loss Improves Health and Health Risks


Reduced CV risk factors

Improved lipid profile

Improved blood pressure

Benefits of 5–10% weight loss

Reduced risk of T2DM

Improved sleep apnea

Improved quality of life

Knowler WC et al. N Engl J Med 2002;346:393–403; Li G et al. Lancet Diabetes Endocrinol 2014;2:474–80; Dattilo AM, Kris-Etherton PM. Am J Clin Nutr 1992;56:320–8; Wing RR et al. Diabetes Care 2011;34:1481–6; Foster GD et al. Arch Intern Med 2009;169:1619–26; Kuna ST et al. Sleep 2013;36:641–9; Warkentin LM et al. Obes Rev 2014;15:169-82; Wright F et al. J Health Psychol 2013;18:574–86.


Clinical Obesity Treatment Modalities

• Self-directed management

• Intensive behavioral therapy

• Structured or medically monitored diets

• Pharmacotherapy

• Medical devices

• Surgical therapy





• Pharmacotherapy

• Medical devices


Guidelines For Behavioral Therapy

• Patients who need to lose weight should receive a comprehensive behavior management program of at least 6 mo (Level A)

• Gold standard is on-site, high-intensity (14+ sessions during initial 6 mo) comprehensive intervention, either individually or in a group setting, delivered by trained interventionist and persisting for at least 1 year (Level A)

• Low-moderate intensity primary care interventions have not been shown to be effective (Level A)

• Other approaches (e.g., web- or phone-based) lead to less weight loss and health improvement (Level B)

AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults. Circulation, 2013.

Counseling• Regular interaction via group or individual contact

– Intensive initial counseling frequency

Diet• Calorie-reduced diet

– 1200-1500 kcal for <250 lb; 1500-1800 kcal for ≥250 lb

Physical activity• 150 minutes/week of moderate activity

• Strength training desirable

Behavioral strategies

• Structured curriculum of behavior change education, including identifying target behaviors and building skills to achieve target behaviors

• Self-monitoring of food intake, physical activity, and/or weight

• Goal setting, problem solving, stimulus control

• Addressing barriers to change

• Behavioral resources (e.g., portion controlled meals)

• Regular feedback and guidance from an interventionist

• Weight maintenance strategies and relapse prevention

Behavioral Therapy for Obesity

Behavioral Therapy in Patients with Obesity and Diabetes

Look AHEAD Research Group. Obesity. 2014;22(1):5-13.

YEAR 1 YEAR 8

92.8

68.0

37.7

15.6

73.6

50.3

26.9

11.0

0

20

40

60

80

100

% o

f Pa

rtic

ipan

ts

>0% ≥5% ≥10% ≥15% >0% ≥5% ≥10% ≥15%

Comorbidity Improvements With Behavioral Therapy

Ch

ange

aft

er 1

yea

r

BMI Category

30 – <3535 - <40> 40

Unick JL, et al. Diabetes Care. 2011;34(10):2152-2157.

What About When Standard Behavioral Therapy Isn’t Enough?

• How do we escalate treatment for those who don’t respond to standard behavioral therapy?

• How do we enhance initial weight loss for those who don’t achieve sufficient weight loss to improve health status/risks?

• How do we enhance longer-term weight maintenance and minimize regain?





• Pharmacotherapy

• Medical devices


Ryan DH, et al. Arch Intern Med. 2010;170(2):146-54.

Very Low Calorie Diet with Meal Replacement Products





• Pharmacotherapy

• Medical devices



beliefs about obesity medications?

A. Weight loss medications are extremely effective; all patients who need to lose a lot of weight should be prescribed medications

B. Weight loss medications are somewhat effective; some, but far from all, patients who need to lose a lot of weight should be prescribed medications

C. Obesity is best treated with judicious diet and exercise behaviors; medications should be avoided as much as possible

D. Weight loss medications don’t work; they should be avoidedE. Weight loss medications are unsafe; they should be avoided

Effect of Weight Loss on Satiety

Kissileff HR, et al. Am J Clin Nutr, 2012.

Before Meal After Meal

Guidelines For Pharmacotherapy• Use pharmacotherapy as adjunct to diet, exercise, and behavioral

counseling for adults… (Level 1, strong evidence)– with BMI 30+; or 27+ with comorbidity;– who are unable to lose and successfully maintain weight; – who meet label indications

• Assess efficacy and safety monthly for the first 3 months, then every 3 months thereafter (Level 2, weak evidence)

• At 3 months, if loss is 5% or more, continue; if not, discontinue and seek alternative approaches (Level 1, strong evidence)

• Use medications to promote long-term weight loss maintenance (Level 2, weak evidence)

• Use weight-losing and weight-neutral medications as first and second line therapy and discuss weight effects of medications with patients (Level 1, strong evidence)

Pharmacological Management of Obesity: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab, 2015.

• 4 FDA-approved short-term medications

– Phentermine accounts for 99% of short-term Rx’s

• 5 FDA-approved long-term medications

– Orlistat (Xenical/Alli)

– Phentermine/topiramate ER (Qsymia)

– Lorcaserin (Belviq)

– Naltrexone/Bupropion SR (Contrave)

– Liraglutide 3.0 mg (Saxenda)

• Off-label options

Obesity Pharmacotherapy

Pharmacotherapy Increases Magnitude and Likelihood of Weight Loss

Wadden TA, et al. Obesity. 2011;19:110-120.

Torgerson JS, et al. Diabetes Care. 2004;27(1):155–161; Smith SR, et al. N Engl J Med. 2010;363:245–256; Fidler MC, et al. J Clin Endocrinol Metab. 2011;96:3067-3077;

O'Neil PM, et al. Obesity (Silver Spring). 2012;20:1426–1436; Allison DB, et al. Obesity (Silver Spring). 2012;20(2):330–342; Gadde KM, et al. Lancet. 2011;377:1341–1352;

Garvey WT, et al. Am J Clin Nutr. 2012;95:297–308; Greenway FL, et al. Lancet. 2010;376:595–605; Apovian CM, et al. Obesity (Silver Spring). 2013;21:935-943;

Wadden TA, et al. Obesity (Silver Spring). 2011;19:110–120; Hollander P, et al. Diabetes Care. 2013;36:4022–4029; Wadden TA, et al. Int J Obes (Lond). 2013;37:1443-1451;

Pi-Sunyer X, et al. N Enlg J Med. 2015;373:11-22.

Pharmacotherapy Increases Magnitude and Likelihood of Weight Loss

>5%

Wei

ght

Loss

(%

)

Long-term Outcomes - 2 Years

Garvey WT, et al. Am J Clin Nutr. 2012;95:297-308


le Roux C et al, 2016.


Torgerson JS, et al. Diabetes Care. 2004;27:155-161.

Hendricks EJ, et al. Obesity 2011.


Long-Term Benefits Require

Long-Term Use

Smith SR, et al. N Eng J Med. 2010;363:245-256.

Outcomes by Responder Status

Smith SR, et al. Obesity. 2014;22:2137-2146.

Pharmacotherapy Improves Weight Maintenance

Wadden TA, et al. IJO. 2013;37:1443-51.

Combination Therapy

Adapted from Wadden, et al. N Eng J Med. 2005;353:2111-2120.

Medication alone

Lifestyle modification alone

Combined therapy

Placebo alone

Orlistat Lorcaserin Phentermine/topiramate ER

Naltrexone/bupropion SR

Liraglutide3.0 mg

WC

BP

LDL

HDL

TG

A1C

HR 0

Diabetes

Pharmacotherapy Improves RFs and Prevents Comorbid Conditions

Progression to Diabetes

Medication (%) Placebo (%)

Lorcaserin (BLOOM/BLOSSOM)

2 3

Phentermine-tpx(2 years) (SEQUEL)

<1 4

Liraglutide (3 years) (SCALE)

3 11

Orlistat (4 years) (XENDOS)

2.9 4.2

Completion and Discontinuation

Completion (%) Discontinuation (%)

Medication Placebo Medication Placebo

Lorcaserin (BLOOM) 55 45 7 7

Naltrexone-Bupropion (COR-1) 50 50 19 10

Phentermine-tpx(CONQUER) 61 43 9 12

Liraglutide (SCALE)

72 64 10 4

Orlistat (XENDOS) 52 34 4 8

Long-Term Cardiovascular Safety

Nissen SE, et al. JAMA 2016.

Long-Term Cardiovascular Safety

Marso SP, et al. NEJM 2016.

Phentermine

• Sympathomimetic amine, blunts appetite

• Approved in 1959 for short-term use, schedule IV

• Dosing: 8 to 37.5 mg qAM; use lowest effective dose

• Contraindications: pregnancy, nursing, MAOIs, glaucoma, drug abuse history, hyperthyroidism

• Relative contraindications: uncontrolled hypertension, tachycardia, history of CAD, CHF, stroke, arrhythmia

• Warnings: primary pulmonary hypertension, valvular heart disease, tolerance, risk of abuse, alcohol

Phentermine [package insert]. Cranford, NJ: Alpex Pharma SA; 2011

Orlistat

• Lipase inhibitor, decreases fat absorption

• Approved 1999; long-term use

• Not scheduled

• 120 mg TID with meals (Rx) or 60 mg TID (OTC)

• Use MVI with fat-soluble vitamins at bedtime

• Contraindications: pregnancy, chronic malabsorption syndrome, cholestasis

• Possible gastrointestinal adverse events

Orlistat [package insert]. South San Francisco, CA: Genentech; 2012; Orlistat [package insert]. Moon Township, PA: GlaxoSmithKline; 2011.

Lorcaserin• Selective 5-HT2C receptor agonist

• Increases satiety

• Approved in 2012 for long-term use; schedule IV

• Single dose: 10 mg BID

• Contraindications: pregnancy

• Warnings: co-administration with serotonergic or antidopaminergic agents, valvular heart disease, psychiatric disorders (euphoria, suicidal thoughts, depression), priapism

• Discontinue if <5% weight loss after 12 weeks of use

BELVIQ [prescribing information]. Woodcliff Lake, NJ: Eisai Inc; 2012.

Lorcaserin: Outcomes by Responder Status

LOR = lorcaserin; PBO = placebo.Smith SR, et al. Obesity. 2014;22:2137-2146.

• Phentermine: sympathomimetic amine; blunts appetite

• Topiramate: increases GABA activity, carbonic anhydrase inhibitor, other; prolongs satiety

• Approved in 2012 for long-term use; schedule IV

• “Recommended” dose: 7.5/46 mg; max: 15/92 mg

• Discontinue if less than 3% weight loss after 12 weeks

• Contraindications: pregnancy (REMS), glaucoma, MAOIs, hyperthyroidism

Phentermine and topiramate extended-release [package insert]. Mountain View, CA: Vivus; 2012.

Phentermine/Topiramate ER

Naltrexone SR/Bupropion SR

• Bupropion: dopamine/NE reuptake inhibitor

• Naltrexone: opioid receptor antagonist; blocks autoinhibition of POMC neurons and amplifies the effect of bupropion

• Not a controlled substance

• Standard dose: 32/360 mg (2 BID)

• Discontinuation if <5% weight loss after 16 weeks

• Black box warning for suicidal thoughts in adolescents

• Contraindications: pregnancy, MAOIs, uncontrolled hypertension, seizure disorders, chronic opioid use

Contrave (naltrexone SR/bupropion SR) prescribing information. Orexigen Therapeutics, La Jolla, CA.

Liraglutide 3.0 mg

• Glucagon-like peptide 1 (GLP-1) receptor agonist

• Liraglutide 1.8 mg FDA-approved in 2010 for T2DM

• Liraglutide 3.0 mg FDA-approved for primary indication of obesity in December 2014

• Not a controlled substance

• Dosing: weekly escalation by 0.6 mg SC

• Discontinue if <4% weight loss at 16 weeks

• REMs: medullary thyroid carcinoma, acute pancreatitis

Saxenda (liraglutide 3.0 mg) prescribing information. Novo Nordisk. Plainsboro, NJ.

Yancy WS, et al. Arch Int Med. 2010;170:136-145.

Choosing Between Options


• Contraindications

• Dual benefits

• Studied populations

Drug factors

• Patient preferences

• Adverse events

• Prior experiences

• Access

Patient factors

• Provider knowledge/comfort

Physician factors

Contraindications and Cautions

Clinical Scenario Avoid/Caution

Elevated seizure risk Naltrexone/bupropion

History of recurrent kidney stones Phentermine/topiramate, orlistat

History of glaucoma Phentermine/topiramate

Uncontrolled hypertension Naltrexone/bupropion, phentermine

Coronary artery disease Phentermine

Moderate-to-severe renal

impairment

Do not exceed half-dose: phentermine/topiramate,

naltrexone/bupropion

Caution: liraglutide, lorcaserin

Moderate-to-severe hepatic

impairment

Do not exceed half-dose: phentermine/topiramate

Do not exceed one-quarter dose:

naltrexone/bupropion

Caution: liraglutide, lorcaserin

SSRI use Caution: lorcaserin

SSRI = selective serotonin reuptake inhibitor.

Dual Benefits

If Patient has

Obesity and…

Consider (But not Explicitly

Approved)…

Smoking Naltrexone/bupropion

Depression Naltrexone/bupropion

Migraines Phentermine/topiramate ER

Diabetes Liraglutide 3.0 mg

Chronic constipation Orlistat

Elevated LDL Orlistat

Studied populations

• Adolescents

• Older adults

• Post-pregnancy

• Menopause

• Post-bariatric surgery

• Extreme obesity

Patients with Extreme Obesity (BMI >45)

Kahan S, et al, 2015.


• Contraindications

• Dual benefits

• Studied populations

Drug factors

• Patient preferences

• Adverse events

• Prior experiences

• Access

Patient factors

• Provider knowledge/comfort

Physician factors

Few Eligible Patients Are Prescribed

Obesity Pharmacotherapy

Zhang S, et al. Obesity Science & Practice.2016;2:104-114.

Prioritize Weight-Losing or Weight-Neutral Medications

Weight Gain Associated With Use

Alternatives (Weight Reducing in Parentheses)

Diabetes Insulin, sulfonylureas, TZDs, mitiglinide

(Metformin), (acarbose), (miglitol), (pramlintide), (exenatide), (liraglutide), (SGLT2 inhibitors)

Hypertension medications

β-blocker ACE inhibitors, calcium channel blockers, angiotensin-2 RAs

Antidepressants and mood stabilizers

Amytriptyline, doxepin, imipramine, nortriptyline, trimipramine, mirtazapine, paroxetine

(Bupropion), nefazodone, fluoxetine

Oral contraceptives Progestational steroids Barrier methods, intrauterine devices

Apovian CM, et al. J Clin Endocrinol Metab. 2015;100:342-62.



• Behavioral tools



• Pharmacotherapy

• Medical devices



beliefs about bariatric surgery?

A. Bariatric surgery is extremely effective and safe; all patients who need to lose a lot of weight should strongly consider surgery

B. Bariatric surgery is somewhat effective and safe; many, but far from all, patients who need to lose a lot of weight should consider surgery

C. Obesity is best treated with judicious diet and exercise behaviors; surgery should be avoided as much as possible

D. Bariatric surgery doesn’t work – I’ve seen people regain all their weight; surgery should be avoided

E. Bariatric surgery is unsafe; it should be avoided

Guidelines For Bariatric Surgery

• Advise patients with BMI >40 (or >35 with

comorbidity) that bariatric surgery may be an

appropriate option to improve health (Grade A)

• Offer referral to an experienced bariatric surgeon

for consultation and evaluation (Grade A)

• Insufficient evidence to recommend for or against

surgery for BMI <35

• No clear guidance for medical devices

AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults. Circulation, 2013.

Medical Devices for Obesity Treatment

Koehestanie P, et al. Ann Surg. 2014. ReShapeMedical.com; Sarr MG, et al. Obes Surg. 2012;22(11):1771-1782.

VBLOCGastric

BalloonsGastric Band

Bariatric Surgery

Sleeve Gastrectomy

Roux-en-Y Gastric Bypass

Sjostrom L, et al. NEJM. 2007;357:741-52.

Bariatric Surgery Has Long Term Data

Buchwald H, et al. JAMA 2004;292:1724-37.

Bariatric Surgery Improves Mortality

Trajectories of Weight Change After Surgery

Courcoulis, et al. JAMA. 2013;310(22).

Adapted from Wadden, et al. NEJM, 2005.

Medication alone

Lifestyle modification alone

Combined therapy

Placebo alone

Combining Modalities Works Better


Wadden TA, et al. NEJM, 2005. Apovian CM, et al. Obesity, 2013. Wadden TA, et al. Obesity, 2011. Halseth A, et al. Obesity 2016.

% W

eigh

t Lo

ss

Medication Surgery

25% BWL

40% BWL


Today

• Obesity epidemiology and background

• Why is it so hard to lose/maintain weight?

• Key clinical guidelines for obesity management

• Evidence-based treatment options for obesity

Thank you

Scott Kahan, MD, MPH

[email protected]

Documents

Obesity Management in Primary Care - American College of ......Obesity Management in Primary Care Scott Kahan, MD, MPH Director, National Center for Weight and Wellness ... B. Obesity