Management of Overweight/Obesity for the Internist
Will Yancy, MD, MHS, FTOS
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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:
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Management of Overweight/Obesity for the Internist
• 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%
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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.
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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
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Management of Overweight/Obesity for the Internist
• 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
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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)
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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.
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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.
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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
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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.
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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
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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
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2013 AHA/ACC/TOS Guideline Algorithm
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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)
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Management of Overweight/Obesity for the Internist
• 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
All Rights Reserved, Duke Medicine 2007
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
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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
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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
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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.
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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.
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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.
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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.
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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
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Management of Overweight/Obesity for the Internist• 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
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
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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
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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.
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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
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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
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QUESTIONS?
Eric Westman, MD, MHSWill Yancy, MD, MHSLifestyle Medicine Clinic4220 North Roxboro StreetDurham, NC 27704Appointments: 919-620-4061
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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.
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2013 AHA/ACC/TOS Guideline Algorithm
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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.
Sherson EA, Family Practice, 2014.
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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.
Sherson EA, Family Practice, 2014.
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