Post on 24-Jul-2020
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
Receive salary and equity compensation for my role as Chief Medical Officer in Form Health, a telemedicine weight management service
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
Introduction – Mr Jean, definition, background
Clinical tools for medical weight management◦ Nutrition
◦ Behavior modification
◦ Physical activity
◦ Medications
Surgical interventions
Devices and experimental options
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
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%
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
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
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
Lizarbe B Front Neurogen 2013
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
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
Jensen MD Circulation 2013; Apovian CM
JCEM 2015;Garvey WT Endocr Prac 2016
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
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
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)
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
Frozen diet meals
Liquid meals
Bars
Portion controlled
Calorie controlled
Convenient
Inexpensive
As part of a sensible
Well-planned menu Wadden TA Obesity 2009
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
01
8
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
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
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)
Number of sessions attended (Look AHEAD)
Wadden TA Obesity 2009
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
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
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
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?”
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
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
When/For whom is it appropriate to consider use?
What are the approved weight loss medications?
Which meds for which patients?
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
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
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
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
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
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
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)
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
ReShape
Intragastricballoons
Maestro VBLOC vagal
blocking therapy
Orbera
Plenity
Aspire Assist
More neurohormonal pathways, more drugs …
ENDOSCOPIC SURGERYALLURION BALLOON
Has lost 50 lbs, BMI 28 kg/m2
Is swimming for exercise
Remains on no medicines, normotensive
HbA1c 5.4%
Feeling great!
Jensen MD Circulation 2013;
Garvey WT Endocr Prac 2016;
Apovian CM JCEM 2015
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”
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