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 &amp; 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