management of overweight/obesity for the internist · suppression test, or late night salivary...

Management of Overweight/Obesity for the Internist

Will Yancy, MD, MHS, FTOS

All Rights Reserved, Duke Medicine 2007

Disclosures for Dr. Yancy

Research Support / P.I. No relevant conflicts of interest to declare

Employee No relevant conflicts of interest to declare

Consultant Nutrisystem, Inc.; University of Pennsylvania/Weight Watchers

Major Stockholder No relevant conflicts of interest to declare

Speakers Bureau No relevant conflicts of interest to declare

Honoraria No relevant conflicts of interest to declare

Scientific Advisory Board No relevant conflicts of interest to declare

Presentation does NOT include discussion of the off-label use of a drug or medical device.

The Department of Medicine requests the following disclosures to the lecture audience:



• Why Pay Attention to Obesity?

• How to Assess Obesity?

• Why and How to Treat Obesity with a Low Carbohydrate, Ketogenic Diets (LCKD)

• How to Treat Obesity with Weight Loss Medications

1995

2005

1990

2000

BRFSS, CDC; Mokdad AH, JAMA, 1999, 2001, 2003; MMWR 2006:55:36

20–24%25–29%≥30%

No data<10%10–14%15–19%

Obesity Trends Among U.S. Adults *Obesity defined as BMI ≥ 30

2007

2011

Obesity Trends Among U.S. Adults *Obesity defined as BMI ≥ 30

2005

2009

BRFSS, CDC; BRFSS, CDC: http://www.cdc.gov/obesity/data/adult.html.

20–24%25–29%≥30%

No data<10%10–14%15–19%


Trends in Prevalence of Overweight and Obesity in U.S.

0

5

10

15

20

25

30

35

40

45

Men Women Men Women

Perc

ent

1960-62 1971-74 1976-80 1988-94 1999-2000 2007-8 2011-12

Overweight (BMI 25-29.9) Obesity (BMI 30+)NHANES data: Flegal KM, Int J Obes, 1998; Flegal KM, JAMA, 2010; Ogden CL, JAMA, 2014.


Recent Developments Regarding Obesity

• Payment for weight management services traditionally self-pay but increasingly covered by payers, including CMS (Medicare) in 2012

• AMA recognized obesity as a disease in 2013• 4 new weight loss medications approved by FDA

since 2012 (none between 1999-2012)• New procedures and devices entering clinical

care– Vagal blocking therapy (VBLOC)– Endoscopic sleeve gastroplasty


What is Obesity?A condition in which excess body fat has accumulated

to such an extent that health may be negatively affected.

How do we measure it?– Weight– Waist circumference or waist-to-hip ratio – Bioelectrical impedance (BIA)– Dual-energy x-ray absorptiometry (DEXA)– CT and MRI – Air displacement plethysmography (Bod Pod)– Underwater weighing– Body mass index (BMI)


Waist Circumference• Perform on patients with BMI 25 - 35 kg/m2

• Where do we measure it (choose one)?– Midpoint between lowest rib and iliac crest– Umbilicus– Narrowest (or widest) circumference– Just below the lowest rib or above the iliac crest

• How?– Bare midriff, standing, arms hanging freely, after exhaling– Non-elastic tape, horizontal to the floor, slight tension

• What is high risk?– Men >40 in. (>102 cm)– Women >35 in. (>88cm)

Klein S, Diabetes Care, 2007.


Utility of Waist Circumference

• Refinement of risk category– 14% of women and 1% of men had a high WC but a

normal BMI (18.5–24.9 kg/m2)

– 70% of women and 25% of men had a high WC but overweight BMI (25.0 –29.9 kg/m2)

• WC is a good predictor of diabetes, CHD, and mortality

• WC provides incremental value above BMI

Klein S, Diabetes Care, 2007.


Assess Possible Secondary Causes of Obesity

• Hypothyroidism– TSH

• Depression– Depressed mood, anhedonia

• Medications• Eating disorders (binge eating, night-eating

syndrome)– Consume large amounts in short period with feeling of

loss of control and subsequent guilt


Assess Possible Secondary Causes of Obesity• Polycystic ovary syndrome

– Hirsutism, acne, irregular menses (late-onset, erratic or heavy/frequent)

– 8 AM total or free testosterone• Cushing’s syndrome

– Weakness, easy bruising, irregular menses, ED– Truncal obesity, moon facies, buffalo hump, striae, acne,

hirsutism– 24-hr urinary cortisol/creatinine, low-dose dexamethasone

suppression test, or late night salivary cortisol– Obesity and depression may cause mild cortisol

elevations

Medications Related to Weight ChangeMedication Classes

Marked Weight Gain

Mild-Moderate Weight Gain

No Weight Change or Weight Loss (↓)

Antidepressants

Clomipramine DoxepinImipramine

Amitriptyline DesipramineMirtazapinePhenelzine

Bupropion (↓) NefazodoneCitalopram NortriptylineDuloxetine Paroxetine Escitalopram ProtriptylineFluoxetine (↓) Sertraline Fluvoxamine Venlafaxine

Mood stabilizers/ anticonvulsants

Valproate Gabapentin

Carbamazepine LithiumLamotrigine Topiramate (↓)Zonisamide (↓)

Antipsychotics

Chlorpromazine ClozapineOlanzapine PerphenazineThioridazineTrifluoperazine

Molindone PimozideFlupentixolQuetiapineFluphenazineHaloperidol Risperidone

ZiprasidoneAripiprazole

Antihistamines - Cyproheptadine Steroid inhalers

Decongestants

Medications Related to Weight ChangeMedication Classes

Marked Weight Gain

Mild-Moderate Weight Gain

No Weight Change or Weight Loss (↓)

AntihypertensivesPropranololTerazosin

DoxazosinPrazosin

ACE Inhibitors Calcium channel blockers

Anti-diabetics

InsulinSulfonylureas Thiazolidinediones

Sitagliptin Acarbose ↓ Liraglutide ↓ Canagliflozin ↓ Miglitol ↓Dapagliflozin↓ Pramlintide ↓Exenatide↓ NateglinideMetformin↓

Contraceptives − Depomedroxy-

progesterone acetate (DMPA)

Other contraceptives

Corticosteroids

Betamethasone Cortisone Dexamethasone Hydrocortisone Prednisone Prednisolone Triamcinolone

− −

Domecq JP, J Clin Endocrinol Metab, 2015; Apovian CM, J Clin Endocrinol Metab, 2015.


Weight History Graph

100

120

140

160

180

200

220

240

260

280

300

Wei

ght i

n lb

s.

Time

CollegeMarried

Pregnancy

Weight Watchers

Knee injured

Mom sick


24-hour Dietary Recall• Breakfast

– Smoothie with banana, frozen berries, low-fat vanilla yogurt, milk

– Special K breakfast bar– OJ and Latte

• Lunch– Chick fil A grilled chicken sandwich with carrot slaw– Diet Coke

• Dinner– Grilled chicken, tossed salad, mashed potatoes– Iced tea with Splenda

• Snacks– Sun Chips and or peanut butter crackers

2013 AHA/ACC/TOS Guideline Algorithm


American Society of Bariatric Physicians®

(ASBP®)

Obesity Algorithm ®

©2014-2015 American Society of Bariatric Physicians: May not be reproduced or altered in any form without written permission from ASBP

Citation:Seger JC, Horn DB, Westman EC, Primack C, Schmidt SL, Ravasia D, McCarthy W, Ferguson U,

Sabowitz BN, Scinta W, Bays HE. Obesity Algorithm, presented by the American Society of Bariatric Physicians, 2014-2015. www.obesityalgorithm.org (Accessed 3/23/15)

http://www.obesityalgorithm.org/


Diets, Carbohydrates, and Calories

2000

Zone Diet

Typical U.S. Diet

Rice Diet

Duke DFC Diet

Car

bohy

drat

e (g

/day

)

200

50

100

200

300

Calories/day1000

(Ketonuria)

Low Glycemic Index Diet

Mediterranean Diet

Protein PowerSouth Beach Phase 1 Atkins Induction

South Beach Phase 2 Atkins Maintenance


Low Carbohydrate Ketogenic Diet (LCKD)

• Initially, < 20 g of carbohydrates per day – Unrestricted amounts of meat and eggs– Four oz. hard cheese– One cup low-carbohydrate vegetables– Two cups salad vegetables

• Calories not restricted• Carbohydrate intake slowly increased as

weight goal approached• Multivitamin and 8 glasses of water daily


Example of 20g Carbohydrate Menu• Breakfast

– Three-egg omelet with avocado– Mozarella cheese with tomato– Bacon (2 strips)– Decaf coffee with cream

• Lunch– Beef round (8 oz.)– Spinach & mixed-leaf salad with mushrooms, onions,

celery, and parmesan cheese– Club soda

• Dinner– Broiled salmon (9 oz.)– Kale topped w/ garlic, lemon, and sesame seeds– Spring water


Low Carb(n = 59)-12.0 kg*

Low Fat(n = 60)-6.5 kg

Weight Trajectories in Low Carb vs Low Fat Trial

Expected means by linear mixed-model analysis *p < 0.001 for time-by-diet group interaction term

Yancy WS, Ann Intern Med, 2004.

Time in weeks

Expe

cted

wei

ght (

kg)

80

85

90

95

100

105

110

0 2 4 6 8 10 12 16 20 24

2 Year Low Carbohydrate Diet Studies

Shai I, NEJM, 2008.

Foster G, Ann Intern Med, 2010.

http://content.nejm.org/content/vol359/issue3/images/large/04f2.jpeg


Santos et al. Meta-Analysis of Low Carb Diet Within Study Arm Results

Variable No. of Reports Net Change 95% CI

Weight, kg 28 -7.0* -7.2, -6.9

LDL-C, mg/dL 22 -0.5 -1.5, 0.6

HDL-C, mg/dL 22 1.7* 1.4, 2.0

TG, mg/dL 19 -29.7* -32.0, -27.4

Santos FL, Obes Rev, 2013. *p ≤0.05 for net change.


Diabetes Outcomes:Low Carb vs Low Fat + Orlistat Study

Variable

LFD / Orlistat (n = 24) Low Carb (n = 22)P value†Wk 0 Wk 48 ∆ Wk 0 Wk 48 ∆

Hgb A1c, % 7.6 7.7 +0.1 7.6 6.9 -0.7* 0.045

Medication score 2.1 1.3 -0.8 1.8 0.5 -1.3 0.27

Medication reduced ≥ 50%

30% 71% 0.01

* p ≤ 0.05, for within-group changes from baseline.† Adjusted for age, sex, race, education, employment, and baseline weight. Mayer S, Diab Obes Metab, 2014.


Symptomatic Adverse EffectsLow fat Low carb

Symptom (n = 60) (n = 59) P valueConstipation 35% 68% < .001Headache 40% 60% .03Bad breath 8% 38% < .001Muscle cramps 7% 35% < .001Diarrhea 7% 23% .02Weakness 8% 25% .01Rash 0% 13% .006

Yancy WS, Ann Intern Med, 2004.


Recommendations for Low Carb Diet• Avoid bread, pasta, rice, potatoes, sugar/sweets/

syrups/desserts, sugared drinks (including juices)• Eat meats, poultry, fish/shellfish, eggs, salad,

vegetables, cheese, avocado, olives, lemon juice, oils

• Daily multivitamin and 8 glasses of water per day• If on medication (esp. for blood pressure or

diabetes), CONSULT A DOCTOR FIRST!• Monitor for: dehydration, low potassium, adequate

sodium intake, constipation, muscle cramps• Add carbohydrates back into diet slowly to

transition to maintenance diet


Management of Overweight/Obesity for the Internist• Why Pay Attention to Obesity?




Apovian CM, J ClinEndocrinolMetab, 2015.

FDA-Approved Weight Loss RxGeneric name PhentermineTrade name (Manufacturer) Adipex-P, Suprenza (multiple)

How it works Amphetamine-like; suppresses appetite

Available doses 15, 30, 37.5 mg

Frequency Once a day (before breakfast or 1-2 hours after)

Cost for 30 day GoodRx.com $30Weight loss (above placebo) 17 lbsCautions See ContraindicationsContraindications -Pregnancy -Overactive thyroid

-Heart disease/stroke -Glaucoma-Uncontrolled high blood pressure -Drug or alcohol abuse-Pulmonary hypertension -MAO inhibitors past 14 days

Drug interactions

Possible side effects Increased heart rate and blood pressure, nervousness, insomnia, tremors, dry mouth, constipation

Notes -Schedule IV controlled substance-Approved for only up to 12 weeks-Do not stop abruptly—decrease dose gradually before stopping

Generic name Phentermine/TopiramateTrade name (Manufacturer) Qsymia (Vivus, 2012)

How it works See phentermine; uncertain for topiramate (anti-seizure med)Available doses 7.5/45 mg, 15/92 mg (3.75/23 mg, 11.25/69 mg for titration)Frequency Once a dayCost for 30 day GoodRx.com $205Weight loss (above placebo) 15 lbs (7.5/45 mg)

19-23.5 lbs (15/92 mg)Cautions -May cause birth defects Risk Evaluation and Mitigation Strategy:

Pregnancy test monthlyContraindications -Pregnancy -Glaucoma

-Overactive thyroid -MAO inhibitors past 14 daysDrug interactions -Lowers blood potassium with thiazide; Topiramate level decreased by

phenytoin or carbamazepine; Increases alcohol, other sedatives’ effect

Possible side effects Nervousness, insomnia, dry mouth, constipation, numbness/tingling, abnormal taste, decreased concentration/ memory, dizziness

Notes -Schedule IV controlled substance-Take 3.75/23 mg x 14d, then 7.5/46 mg; if <3% weight loss at 12 wks, increase to 11.25/69 mg for 14d, then 15/92 mg-7.5/46 mg max if mod. kidney/liver disease-Seizures can occur if stopped abruptly!

Generic name LorcaserinTrade name (Manufacturer) Belviq (Eisai, 2012)

How it works Activates serotonin 2C receptor in brain to suppress appetite

Available doses 10 mgFrequency Two times a day

Cost for 30 day GoodRx.com $240Weight loss (above placebo) 6.5-8 lbsCautions May cause serotonin syndrome or Neuroleptic Malignant Syndrome

May cause heart valve problems

Contraindications -Pregnancy, breastfeeding-Taking cabergoline

Drug interactions Monitor or avoid if taking dextromethorphan, depression meds (SSRIs, SNRIs, MAOIs, bupropion, lithium, St John’s Wort), anti-psychotics, triptans (for migraines), tramadol, tryptophan, linezolid, ED medications

Possible side effects Headache, nausea, dizziness, fatigue, nausea, dry mouth, constipation, slowed thinking, hallucinations, slow heartbeat, painful erections, decreased blood cell counts, breast milk (women) or enlargement (men)

Notes -Schedule IV controlled substance-Discontinue if less than 5% weight loss at 12 weeks

Generic name Naltrexone/BupropionTrade name (Manufacturer) Contrave (Orexigen; Takeda, 2014)How it works Increases POMC neuron activity to regulate food intake in hypothalamus

(appetite center) and mesolimbic dopamine circuit (reward system)Available doses 8 mg/90 mgFrequency Two pills two times a day (see notes for titration)Cost for 30 day GoodRx.com $240Weight loss (above placebo) 5-9 lbsCautions Bupropion may cause increased suicidal thoughts in youth with depression

Naltrexone may cause opioid overdose OR withdrawal symptoms in people taking opioids

Contraindications -Pregnancy -Taking opioid pain medications-History of seizures -Uncontrolled blood pressure-History of anorexia, bulimia-Excessive EtOH or sudden stopping of EtOH/benzo/barbiturate

Drug interactions -CYP2B6 inhibitors (clopidogrel) - MAO inhibitors past 14 days -Can cause false + amphetamine drug test

Possible side effects -Nausea, constipation, headache, vomiting, dizziness, trouble sleeping, dry mouth, diarrhea, liver damage, manic episodes, glaucoma

Notes -Titrate weekly: 1 pill AM; 1 pill twice a day, 2 pills AM/1 pill PM; 2 pills twice a day (max dose)-“Scale Down” program is free

Generic name OrlistatTrade name (Manufacturer) Xenical (Genentech, 1999)

Alli (GlaxoSmithKline; OTC)How it works Blocks absorption of 1/3 of fat in a mealAvailable doses 120 mg

60 mg (Alli)Frequency Three times a day (with meals)Cost for 30 day GoodRx.com $540; $50 (Alli)Weight loss (above placebo) 5.5-7 lbsCautions May increase risk for oxalate kidney stones or liver failure

Contraindications (Do NOT take if…)

-Gallstones-Chronic malabsorption

Drug interactions May increase effect of warfarin (Coumadin)-Decreases cyclosporine blood level-May decrease thyroid supplement levels

Possible side effects -Flatulence, oily stools, BM urgency-Symptoms are worse if meals are high fat

Notes -Take within 1 hour of meal containing fat-Omit dose if meal is skipped or contains no fat-Take daily multivitamin (with A,D, E and K) at least 2 hours prior

Generic name LiraglutideTrade name (Manufacturer) Saxenda (Novo Nordisk)

(Victoza for diabetes)

How it works glucagonlike peptide-1 (GLP-1) receptor agonistAvailable doses 3.0 mg

(1.2 or 1.8 mg for diabetes)

Frequency Once a day, subcutaneous injectionCost for 30 day GoodRx.com ?

Weight loss (above placebo) 12-13 lbs

Cautions May cause gallbladder attack or pancreatitisMay increase risk of thyroid cancer

Contraindications (Do NOT take if…)

History of (or family history of) medullary thyroid carcinoma or multiple endocrine neoplasia (MEN) type 2

Drug interactions Increased risk for low blood sugar if taking diabetes medication

Possible side effects -Nausea, vomiting, diarrhea, constipation, low blood sugar if taking diabetes medication

Notes -Discontinue if less than 4% weight loss at 16 weeks


How to Write a Prescription for Diet or Physical Activity

• Don’t!

• Instead, help the patient write out goals and an action plan

• Use the 5 A’s to open the conversation and motivate/steer behavior change

• Use S-M-A-R-T acronym to set smart goals


5 A’s• Ask permission to discuss weight; be

nonjudgmental; explore readiness for change• Assess BMI, waist circumference; explore drivers

and complications• Advise about health risks, benefits of weight loss,

need for a long-term strategy, tx options• Agree on realistic weight-loss expectations,

behavioral changes, specific treatment plans• Assist in identifying /addressing barriers; provide

resources; Arrange follow-up

Sherson EA, Family Practice, 2014.


SMART Behavioral Goals• Specific

– I will eat celery sticks with cream cheese instead of potato chips for evening snack 5 days a week

• Measureable / Monitor– Mark on calendar each night it’s done

• Attainable– 7 days a week too difficult and would derail goal

• Relevant– I eat a bag of potato chips every evening

• Time-bound– Reassess progress in 2 weeks


Summary

• Obesity prevalence has increased markedly, causing major health problems

• Assessing weight should be done systematically to detect underlying causes or associated disease

• Low carbohydrate diets are another viable option for weight loss and metabolic management

• More and a greater variety of weight loss medications are available

• Use 5 A’s and SMART goals to aid behavior change


QUESTIONS?

Eric Westman, MD, MHSWill Yancy, MD, MHSLifestyle Medicine Clinic4220 North Roxboro StreetDurham, NC 27704Appointments: 919-620-4061


Hu et al. Meta-Analysis of RCTs of Low Carb vs Low Fat Diets

Variable No. of Trials Net Difference 95% CI

Weight, kg 22 -1.0 −2.2, 0.2

LDL-C, mg/dL 19 3.7* 1.0, 6.4

HDL-C, mg/dL 19 3.3* 1.9, 4.7

TG, mg/dL 20 -14.0* −19.4, −8.7

Hu T, Am J Epidemiol, 2012.

*p ≤ 0.05 for net change.


2013 AHA/ACC/TOS Guideline Algorithm


5 A’s• Ask

– How do you feel about your current weight?– Tell me what you do for exercise.

• Assess– Did you have issues with overeating before you

were diagnosed with depression?• Advise

– I think weight loss could really help the arthritis in your knees.

– Changing the way you eat and increasing your exercise could go a long way toward preventing diabetes.



5 A’s• Agree

– I believe your goal to lose 20 pounds in 6 months is a realistic goal. That’s about a pound a week. Let’s discuss ways you think you can achieve this.

• Assist / Arrange– How do you think your family could support you

in eating better?– Here is information on low cost group physical

activity classes at the YMCA near your house.– I would like you to call me in 2 weeks to let me

know how your weight loss plan is going.


management of overweight/obesity for the internist · suppression test, or late night salivary...

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