Florencia Halperin, MD, MMSc · Florencia Halperin, MD, MMSc Medical Director, Program for Weight...
Transcript of Florencia Halperin, MD, MMSc · Florencia Halperin, MD, MMSc Medical Director, Program for Weight...
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Obesity Management
Florencia Halperin, MD, MMScMedical Director, Program for Weight Management
Division of Endocrinology, Brigham and Women’s Hospital
Instructor in Medicine, Part-time, Harvard Medical School
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Receive salary and equity compensation for my role as Chief Medical Officer in Form Health, a telemedicine weight management service
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At the end of this class, participants will be able to:
Apply the approach that obesity is a disease, not a behavioral problem
Understand how to formulate an effective obesity treatment program with multiple components
Know indications for and recent advances in approved obesity treatments -including lifestyle interventions, pharmacotherapy, surgeries and devices
Be familiar with obesity management guidelines
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Introduction – Mr Jean, definition, background
Clinical tools for medical weight management◦ Nutrition
◦ Behavior modification
◦ Physical activity
◦ Medications
Surgical interventions
Devices and experimental options
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57 y.o. man
Has known OSA
Takes no medications
SH: Married, kids, MBTA bus driver (12p-12MN)
FH: Mo, Fa T2D. Fa died, renal complications
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Obesity History:◦ Childhood – Normal weight. Age 18: 190 lbs – lean, athletic, “sexy”◦ Quit smoking 4 years ago, gained 50 lbs◦ Previous weight-loss attempts: none
Dietary history:◦ Breakfast: bagel, coffee at donut shop◦ Lunch: parks his MBTA bus near Fast Food◦ Dinner: Gets home late, whatever his wife has made for dinner – protein, starch, veggie◦ Snacks: chips, candy at vending machine on breaks◦ Alcohol: 5-6 drinks every weekend◦ Other Drinks: 5 grape sodas/day
Exercise: “No time” Physical Exam: Weight 252 lbs, BMI 35.1 kg/m2, obesity Labs: HbA1c 6.2%
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A. That given his degree of excess weight he lose 1-2 lbs/wk until reaches normal BMI of 24.9
B. That he lose 5-10% of initial weight over next 6 mos
C. That he lose 5-10% of initial weight over next 12 mos
D. That he lose weight, with the goal of losing whatever he self-determines to be obtainable
E. An individualized weight loss goal based on risk factors, determined by the interactive algorithm that can be accessed online as part of the 2013 AHA/ACC/TOS guidelines
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A. Guidelines suggest prescribing caloric restriction for weight loss: 1,200 -1,500 kcal/day for women and 1,500-1,800 kcal/day for men
B. Guidelines suggest that a low-carbohydrate, low glycemic index approach is preferred for diabetes risk reduction and longer term weight loss maintenance
C. Self-monitoring by tracking food intake is associated with successful weight loss, but monitoring weight is associated with worse outcomes
D. Physical activity can augment weight loss, but beyond 150 mins/week little added benefit is observed
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Body Mass Index (BMI): kg / m2
Overweight: BMI 25.0 – 29.9
Obesity: BMI > 30.0Class I: BMI 30.0 – 34.9
Class II: BMI 35.0 – 39.9
Class III: BMI > 40
Obesity is defined as a chronic, relapsing, multi-factorial,
neurobehavioral disease, wherein and increase in body fat
promotes adipose tissue dysfunction and abnormal fat mass
physical forces, resulting in adverse metabolic,
biochemical and psychosocial consequences–American Society of Bariatric Physicians
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Lizarbe B Front Neurogen 2013
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Gardner IJO 2012; Church PLoSONE 2009; Smith S NEJM 2010
Placebo
Lorcaserin 10 BID
Lorcaserin 15 QD
Lorcaserin 10 QD
DIETARY INTERVENTIONS
EXERCISE INTERVENTIONS
PHARMACOTHERAPY
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Look AHEAD Research Group Diabetes Care 2007; LookAHEAD
Group NEJM 2013; Li G Lancet Diab Endocrin 2014
LookAHEAD RCT Intensive Lifestyle
(8.6% weight loss)
Education Only
(0.7% weight loss)
P
A1c (%) -0.64 -0.0 0.001
Systolic BP (mmHg) -6.8 -2.8 0.001
Diastolic BP (mmHg) -3.0 -1.8 0.001
LDL (mg/dl) -5.2 -5.7 0.49
HDL (mg/dl) +3.4 +1.4 0.001
TG (mg/dl) -30.3 -14.6 0.001
CVD/Mortality?
• LookAHEAD: No difference in CV death, nonfatal MI, CVA, hospitalization
angina at 10 yrs
• Da Qing: RCT 6 yrs, 23 yr followup, CV death HR 0.59, all mortality HR 0.71
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Jensen MD Circulation 2013; Apovian CM
JCEM 2015;Garvey WT Endocr Prac 2016
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AACE Guidelines: “The principal outcome and therapeutic target in the treatment
of obesity should be to improve the health of the patient by preventing or treating weight-related complications using weight loss, not the loss of body weight per se.”
AHA/TOS Guidelines: 5-10% in 6 mos
Garvey WT Endocr Prac 2016
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Nutrition
Caloric restriction
Portion controlled foods
Diet Quality
Behavioral Strategies
Frequent follow ups: accountability, support, structure
Self monitoring: Weight, diet, physical activity
SMART goals
Physical Activity
Putting it all together
Comprehensive programs, including commercial ones
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6 months: 6 kg (7%) weight loss
2 years: 3-4 kg weight loss
Irrespective of macronutrient composition
Sacks FM NEJM 2009
Bottom line for weight loss: Caloric restriction and
adherence (not macronutrient composition)
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AACE Guidelines
Reducing caloric intake should be the main component of any weight-loss intervention (500-750 kcal/d energy deficit)
Meal plans can include: Mediterranean, DASH, low-carb, low-fat, volumetric, high protein, vegetarian
AHA/ACC/TOS Guidelines
1,200-1,500 kcal/d for women
1,500-1,800 kcal/d men
OR 500-750 kcal/d energy deficit
One of the evidence-based diets that restricts certain food types (e.g. high-carb, high-fat) in order to create an energy deficit by reduced food intake
Garvey WT Endocr Prac 2016;
AHA/ACC/TOS Guidelines Circulation 2013
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Frozen diet meals
Liquid meals
Bars
Portion controlled
Calorie controlled
Convenient
Inexpensive
As part of a sensible
Well-planned menu Wadden TA Obesity 2009
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DIETFITS
RCT (n=609): Healthy low carb (limit rice, cereal, bread, pasta) vs. healthy low fat (limit fatty meat, whole dairy)◦ No restrictions on total calories
Weight change (12 mos): −5.3 kg LF vs −6.0 kg LC (ns)
Low carb diet not better for insulin resistance
Genotypes (implicated in fat/carb metabolism): ◦ No correlation with weight lost
Ga
rdn
er
CD
et a
l. J
AM
A 2
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N=20, inpatient
Ad libitum intake
Ultra-processed vs un-processed, matched for macros
Processed ◦ Ate ~500 cal/d more
◦ Gained ~ 1 kg
Unprocessed◦ Ate ~500 cal/d less
◦ Lost ~ 1 kg
Hall et al., 2019, Cell Metabolism 30, 1–11
Calories
Weight +0.9Kg
-0.9 kg
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Not just “a diet”, it is lifestyle change – an iterative and sustainable process
It’s not one-size-fits-all – what can be sustainable is different for different people
Calories and portions matter
Food quality is also important ◦ Whole foods (over processed foods)
◦ Protein and fiber help with satiety
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Improve self-efficacy: anticipate/overcome barriers
Goal setting: S.M.A.R.T. (Specific, Measurable, Achievable, Realistic, Timely) goals
Self-monitoring (weight, food, exercise)
Eating to hunger
Support (frequent follow up visits – 14 weeks in 6 mos)
Stress management/reduction
Healthy sleep
Long-term partnership with patients (dance, not wrestle)
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Number of sessions attended (Look AHEAD)
Wadden TA Obesity 2009
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Low fitness independent predictor of mortality for any BMI
Exercise alone: limited effect on weight loss
Exercise plus diet: augments loss (modest)
Weight loss maintenance: More is better (>300 mins/week)
Shaw K Cochrane 2006; Saris WH Obes Rev 2003; Bravata DM JAMA 2007Wadden TA Circulation 2012
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The most effective behavioral weight loss treatment is a high intensity comprehensive program◦ In-person
◦ High-intensity (i.e., ≥14 sessions in 6 months)
◦ Individual or group sessions by trained interventionist
◦ Moderately-reduced calorie diet
◦ Increased physical activity
◦ Use of behavioral strategies to facilitate adherence
AHA/ACC/TOS Guidelines Circulation 2013
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Caloric restriction: 1500-1800 cal/day◦ Drink water (no soda)
◦ Breakfast from home; Bring lunch (leftovers) and healthy snacks/avoid machines
◦ Walk on breaks; more moving with his family on weekends – sport with older kids, walking with stroller
Agrees to intensive lifestyle program (“really freaked out by diabetes risk”)◦ Weekly weigh-in, dietitian visit, group session
◦ 1500 kcal/day diet with 3 liquid meal replacements/day
◦ Food, weight and exercise logs
◦ Join gym to go before shifts
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Month 1-2: Goes weekly to intensive lifestyle program◦ Loses 15 lbs (6%)
Months 3-6: Boss less flexible, misses a lot of visits◦ Regains 4 lbs, still down 11 lbs (4%)
Months 6-12: Continues with intermittent RD visits, meal replacements and logging, and gym◦ Weight stable at 240 lbs◦ Gets diagnosed with HTN, starts HCTZ
Month 15: ◦ Frustrated, complains of feeling extremely hungry when “on track”◦ “Isn’t there anything else Doc?”
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A. Yes, because he has a BMI > 27 with 2 weight-related complication (OSA, HTN)
B. Yes, because weight loss medication should be employed for all individuals with BMI >25 kg/m2
C. No, because he has not tried a very low–calorie diet in a high intensity weight loss program
D. No, because his BMI is < 40 kg/m2
E. C and D
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A. Discontinuation of the medication once the patient has lost 5% of initial body weight
B. Discontinuation of the medication after 3 mos(regardless of effect)
C. Discontinuation if the patient does not lose 5% of initial body weight at 3 mos
D. Change to use as needed once the patient loses 5% of initial body weight - to lower exposure/risks
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When/For whom is it appropriate to consider use?
What are the approved weight loss medications?
Which meds for which patients?
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Adjunct to diet and exercise
Indication: BMI >30; BMI >27 with co-morbidities
If never participated in a comprehensive lifestyle intervention program, undertake such a program prior
If unable to lose or sustain weight loss with comprehensive lifestyle intervention and meets BMI criteria, adjunctive therapies may be considered
AHA/ACC/TOS Guidelines Circulation 2013
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1. Maximize lifestyle efforts first. If unable to lose or sustain, then consider adjunctive pharmacotherapies
2. Assess response monthly for first 3 mo, then every 3 mo
3. If ineffective (weight loss <5% at 3 mo): discontinue
4. If effective (weight loss 5% at 3 mo): continue
AHA/ACC/TOS Guidelines Circulation 2013; Apovian CM JCEM 2015;
Smith SR NEJM 2010; Fidler MC JCEM 2011
Weight loss0
High
Responders
Lorcaserin x1 yr, then re-
randomize to continue vs stop
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NameWeight
Loss*Mechanism Side Effects Dose Other
Phentermine 5%Adrenergic/
CNSHR, BP
15-37.5
mg QAMGeneric
Phentermine/
Topiramate
(Qsymia)7-9%
Adrenergic/
CNS
HR, BP,Cognitive
Teratogenic
3.75/2 mg
(14d)
7.5/46 mg
QAM
QMO U HCG;
1mo chem↓CO2;
Not in CAD, CVA
in last 6mo
Lorcaserin
(Belviq)3.5%
5-HT2c
receptor
agonist
Headache10 mg
BIDNot with SSRI
Orlistat
(Alli,Xenical)3%
Lipase
InhibitorSteatorrhea
60-120
mg QAC
Vitamin
deficiencies
Naltrexone/
Buproprion
(Contrave)4% CNS
Nausea
Constipation
Headache
8/90 mg:
2 tabs BID
(titration)
Not with other
bupropion,
opioids
Liraglutide
(Saxenda)8-9%
GLP-1
agonist/CNS
Nausea,
Diarrhea
3 mg SC
QD
*Above placebo
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Effectiveness
Contra-indications◦ Based on medical conditions or med-med interactions
Possible benefit for multiple medical conditions◦ Headache prevention (topiramate)
◦ Diabetes/Pre-diabetes (liraglutide)
Cost
Patient Preference
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First report of CV safety of a pharmacologic strategy
12,000 overweight/obese with CVD or multiple RFs
1ry safety outcome: major events (CV death, MI, CVA)
Outcomes: No increase in CV risk; No difference in major adverse CV outcomes
~20% reduction in new onset T2D (HR 0.81)
WITHDRAWN FROM THE MARKETFeb 2020
• At 5 yrs, occurrence of cancers in DRUG GROUP 7.7%,
• Compared to 7.1% in the PLACEBO GROUP
• Several types - pancreatic, colorectal, and lung
It is still uncertain whether lorcaserin truly increases the risk
of cancer, mechanism, etc
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Metformin Severe diarrhea
Liraglutide Severe exhaustion
PHEN+TOP non-responder, lost 3 lbs in 3 mos
Lorcaserin non-responder, gained 1 lb in 3 mos
Has lost and regained 15 lbs in 2 years
Has made a lot of positive lifestyle changes
BMI is now up to 37 kg/m2 and he wants to get rid of this weight
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Indications: BMI >40; BMI >35 with co-morbidities
2011 2014
Total 158,000 193,000
RYGB 36.7% 26.8%
LAGB 35.4% 9.5%
SG 17.8% 51.7%
Ponce J SOARD 2015
(LAGB) (RYGB) (SG)
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LAGB SG RYGB
Weight Loss
(2 yrs)40-45% EBW 50-60% EBW 60-70% EBW
Length of
Surgery1 hour 1 hours 2 hours
Time in Hospital 1 day 2 days 2 days
Risk of Death <0.05 % 0.1-0.3 % 0.3-0.5 %
Reversal of
Procedure
Yes, if medically
necessaryNo Very Difficult
Other IssuesInadequate loss;
Band removal
Dumping
syndrome
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ReShape
Intragastricballoons
Maestro VBLOC vagal
blocking therapy
Orbera
Plenity
Aspire Assist
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More neurohormonal pathways, more drugs …
ENDOSCOPIC SURGERYALLURION BALLOON
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Has lost 50 lbs, BMI 28 kg/m2
Is swimming for exercise
Remains on no medicines, normotensive
HbA1c 5.4%
Feeling great!
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Jensen MD Circulation 2013;
Garvey WT Endocr Prac 2016;
Apovian CM JCEM 2015
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Obesity is a disease, not a behavioral problem
One size does not fit all: Personalize treatment plan
Weight loss linked to health goals
Chronic disease management: patient-centered partnership
5-10% weight in 6 mos is achievable◦ Calorie restriction, Behavioral Strategies, Exercise
◦ Meds: adjunct to lifestyle therapy, re-assess effect
◦ Surgery: RYGB, SG highly effective in “diabesity”
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1. Jensen MD, et al. 2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults. Circulation. 2014 Jun 24;129(25 Suppl2):S102-38.
2. Apovian CM, et al. Pharmacological Management of Obesity: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2015 Feb;100(2):342-62.
3. Garvey WT, et al. American Association of Clinical Endocrinologists and American College of Endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity. Endocr Pract. 2016;22(Suppl 3):1-203
4. Mechanik, JI, et al. Clinical practice guidelines for the perioperative nutritional, metabolic, and nonsurgical support of the bariatric surgery patient--2013 update: cosponsored by American Association of Clinical Endocrinologists, The Obesity Society, and American Society for Metabolic & Bariatric Surgery. Obesity (Silver Spring). 2013 Mar;21 Suppl 1:S1-27
5. Heymsfield SB and Wadden TA. Mechanisms, Pathophysiology, and Management of Obesity. N Engl J Med 2017; 376:254-266
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