Lifestyle Medicine: Tools for Promoting Healthy Change

Obesity and Metabolic Risk: Different

Disorders, Different Treatments
Lee M. Kaplan, MD, PhD
Obesity, Metabolism & Nutrition Institute
Massachusetts General Hospital
Harvard Medical School

LMKaplan@partners.org

May 4, 2019
Fernando Botero, 1932-
Disclosures

• Scientific advisor, AMAG Pharmaceuticals

• Scientific advisor, Amgen
• Scientific advisor, Gelesis
• Scientific advisor, GI Dynamics
• Scientific advisor, Johnson & Johnson
• Scientific advisor, Novartis
• Scientific advisor, Novo Nordisk
• Scientific advisor, Rhythm
• Scientific advisor, Sanofi
• Medical Advisor, United HealthCare System
• Scientific advisor, U.S. National Institutes of Health
• Scientific advisor, United Kingdom All-Party Parliamentary Group on
Obesity, the U.K. Medical Research Council
• Scientific advisor, U.S. Food and Drug Administration
• Scientific advisor, U.S. Department of State
What is Obesity?

Excessive total body fat

that presents a risk to health

• The presence and severity of obesity can be measured

by body composition analysis

• It can be estimated by a variety of biomarkers

• Body mass index (BMI)
• Height-waist circumference ratio
• Body fat distribution
• Risk scores
• Comorbidities

• But these markers should not define obesity

The Story of Obesity Prevention

• Rates of obesity continue to climb

• Obesity rate in US adults now 38% - highest ever
• The rest of the world is catching up
• 6 countries with even higher obesity rates than the US
• NO country with falling obesity rates

• This growth continues despite increasing knowledge about the

health benefits of exercise and healthy diets

• What are we missing?

• Is obesity really a volitional problem?
• What are the non-volitional drivers?
• Genetics? Environment? Others?
The First Question

Is obesity really a disease?

The answer to this question ultimately determines – and

drives – the appropriate approach to obesity, along with
the tools, clinical strategies and payment policies
developed to support that approach
Arguments that Obesity is NOT a Disease

• It is a lifestyle choice

• No specific symptoms associated with it

• It is a risk factor for disease, not a disease itself*

• Calling it a disease would define one-third of Americans as
being sick and could lead to more reliance on costly drugs
and surgery**

* What about high cholesterol or hypertension?

** What about the combined prevalence of hypertension, dyslipidemia,
and diabetes?
Why Obesity IS a Disease

• It is associated with impaired body function

• Like other diseases, it results from physiological

dysfunction
• Though frequently precipitated by environment forces in
modern society, the final common pathway of obesity
reflects abnormal physiology

• It causes, exacerbates or accelerates more than 200

comorbid diseases

• It is associated with a substantial burden of morbidity and

premature death
Medical Complications of Obesity

Metabolic

Structural

Inflammatory
229+ comorbidities
Degenerative affecting EVERY
organ system and
Neoplastic medical specialty

Psychological
Yuen M … Kaplan LM , Obesity Week 2016
Implications of Obesity as a Serious Disease

• You work to understand it

• Research commensurate with the magnitude and severity of
the problem
• Broad-based approach using epidemiological, basic,
translational, clinical, and health services approaches

• You try to prevent it

• You try to treat it effectively – always
• You aim for efficient treatment
• Aim is for the best combination of benefit and risk
• Not the maximal benefit regardless of the risk
• Not the minimal risk regardless of the benefit

• This is straightforward - you do it for all other diseases

• But what is your treatment strategy?
The Second Question

Obesity is the major contributor to metabolic risk

Why can’t we just apply the known benefits of

lifestyle treatment to obesity?
Some Demonstrated Benefits of Exercise …

… on Metabolic Risk … on Obesity

• Reduces elevated blood • Modestly prevents weight

pressure regain
• Improves blood lipid profile • Does not induce significant
weight loss
• Decreases cardiovascular risk
• Prevents type 2 diabetes
• Improves existing type 2
diabetes
• Improves cognition
• May decrease cancer risk
Some Benefits of a Low Carbohydrate Diet …

… on Metabolic Risk … on Obesity

• Prevents type 2 diabetes • Associated with accelerated

short-term weight loss
• Improves existing type 2
diabetes • Associated with modest
long-term weight loss
• Improves lipid profile
• Decreases cardiovascular risk
• Decreases cancer risk
 The effects of lifestyle modification on obesity are
far less profound than their effects on metabolic risk

… but obesity is the major cause of metabolic risk

How could this be?

What is the Relationship between A and B?

1. A causes B

A 2. B causes A
3. A interferes with B
C 4. B interferes with A
5. There is no relationship
B 6. We don’t know
WhatAbout
How is the This
Relationship between A and B?
Relationship?

A
Mediterranean

Diet
 CV
? C
Risk

B
Weight
Loss
The Third Question

Do we understand obesity well enough to

treat it effectively?
Competing Models of Energy Balance Regulation

Purposeful behavior
drives
the physiology of
energy balance
regulation

Implications
• Increased caloric intake
drives weight gain
• All types of calories
have similar effects
• Physical activity causes
weight loss directly by
burning calories
Implication of the Purposeful Behavior Model …

That obesity in modern society is caused primarily by increased

availability and accessibility of food
… at a low financial and energy cost

Primary assumption of this model:

We have evolution-derived protections against starvation, but not
against obesity

Problems with this assumption:

• Food has been abundant through most of mammalian evolution;
predation is the greater risk
• The inefficiencies of carrying excess weight are more than sufficient
to promote evolutionary protection (a 0.1% advantage is selected for)
• There are at least 210 genes that when mutated lead to obesity,*
indicating that for each of them, one of their roles is to help protect
against obesity
*Herzog L, Kaplan LM, unpublished
Think About This …

• Why do people gain weight when started on selected

medications? (the medications don’t have many calories)
• Insulin
• Sulfonylureas (all)
• Corticosteroids (all)
• Mood stabilizers (esp. clozapine, olanzapine, venlafaxine)
• Anti-seizure medications (esp. valproate, oxcarbazepine)
• b-blockers (all)

• Why do people gain weight when sleep deprived?

• Why do people gain weight when chronically stressed?

Competing Models of Energy Balance Regulation
Purposeful behavior
drives
the physiology of vs.
energy balance
regulation
Implications
• Increased caloric intake
drives weight gain
• All types of calories
have similar effects
• Physical activity causes
weight loss directly by
burning calories
The physiological
regulation of energy
balance
drives
behavior
Implications
• Changes in the modern
diet alter energy balance
physiology
• The chemical nature of
the calories is critical
• Re-regulation of
abnormal physiology is
essential for success
The Normal Physiology of Energy Balance

• Average adults require approximately 1300 kcal/day*

• Average adults consume 2000-2500 kcal/day
• Average adults thus consume 1.5-2 times as much food as needed
• Excess intake is available for physiological emergencies
• Maintenance of normal fat stores (and body weight) requires
precise disposal of 40-50% of ingested calories daily
• Maintaining weight within 20 lbs. between ages 21 and 65
requires matching of intake and expenditure within 0.2%
• Corresponds to accuracy of 4-5 kcal/day
• Less than one-half potato chip

Thus, daily energy balance must be a

tightly regulated physiological trait
The Body Seeks a Stable Adipose Tissue Mass

Similar to other regulated tissue mass

• Liver
• Red blood cells
Feedback Regulation of Energy Metabolism

Environmental
GI Tract sensing Muscle Liver
Sensory Organs Bone

Irisin

Metabolic
activity and
Energy needs
stores

Food intake
Leptin Nutrient handling
Energy expenditure

This process is critical

to life and involves Adipose
nearly 20% of the
human genome tissue
Environmental Drivers to Obesity

Labor-saving devices Chronic stress and distress

(decreased physical activity) (incl. sleep, circadian)
(effects on muscle more than calories) (direct impact on relevant brain areas)

Altered Medications
food supply (up to 10% of obesity)
(signaling more
than calories)

These influences act by raising the fat mass set point

The Modern Environment Causes Obesity by Driving
Up the Defended Fat Mass

Body fat mass set point

Body fat mass set point

Body fat mass set point

Abnormal Unhealthy Sleep Chronic Disrupted Weight

dietary
Abnormal muscle
Unhealthy deprivation
Sleep stress
Chronic circadian
Disrupted gain
Weight
constituents
dietary muscle deprivation stress rhythms
circadian inducing
gain
constituents rhythms medications
inducing
medications

Years of Exposure
Implications for Obesity Treatment
Obesity and Its Care: A Battle of Forces that
Influence the Fat Mass Set Point

Lifestyle Modification
Regular Bariatric
Anti-Obesity
More and Surgery Stable
Medications Weight
Healthy physical better Stress eating stabilizing
diet activity sleep reduction patterns alternatives

Body fat mass set point

Abnormal Unhealthy Sleep Chronic Disrupted Weight

dietary muscle deprivation stress circadian gain
constituents rhythms inducing
medications
Years of Exposure
Obesity Treatment Strategy

A Stepwise – and Additive – Approach

(progress through algorithm as clinically required)

Post-surgical Combinations

Weight Loss Surgery

Pharmacotherapy

Professionally-directed Lifestyle Change

Self-directed Lifestyle Change = Patient Education

40+ Current Treatments of Obesity

Lifestyle Pharmacological Medical Devices

Low calorie diet Phentermine Adjustable gastric band
Low-carbohydrate diet Topiramate Vagal nerve block
Low-fat diet Zonisamide Gastric balloon
Low glycemic index diet Metformin Gastric aspiration
Paleo diet Lorcaserin Gelesis 100 capsules
Mediterranean diet Bupropion
Very low calorie diet Naltrexone Endoscopic
Aerobic exercise Exenatide Gastric plication
Resistance training Liraglutide
Semaglutide
Sleep enhancement Surgical
Dulaglutide
Circadian enhancement Pramlintide Sleeve gastrectomy
Stress reduction Orlistat Gastric bypass
Motivational interviewing Diethylpropion Biliopancreatic diversion
Cognitive-behavioral Leptin Duodenojejunal bypass
therapy Canagliflozin
Empagliflozin
Replace weight gain-
promoting medications
Core Principles of Obesity Treatment

1. The goal of effective treatment is to reduce the

elevated fat mass set point

2. There is wide heterogeneity in the causes and

manifestations of obesity

3. This leads to wide patient-to-patient variability in

the response to all anti-obesity therapies
Weight Loss Varies Widely Among Patients

Diet (Low-carbohydrate) Drug (Liraglutide)

30 30
25 25
Patients (%)

20 20
15 15
10 10
5 5
0 0

Device (Duodenal liner) Surgery (Gastric Bypass)

30 30
25 25
Patients (%)

20 20
15 15
10 10
5 5
0 0
5-10 Gain

0-5

40-45
10-15 Gain

0-5 Gain

10-15
15-20
20-25
25-30
30-35
35-40

45-50
5-10

0-5
5-10 Gain

>50
0-5 Gain

10-15
15-20
20-25
25-30
30-35
35-40
40-45
45-50
10-15 Gain

5-10
Core Principles of Obesity Treatment

1. The goal of effective treatment is to reduce the

elevated fat mass set point

2. There is wide heterogeneity in the causes and

manifestations of obesity

3. This leads to wide patient-to-patient variability in the

response to all anti-obesity therapies

4. People who respond to one therapy may not respond

to another, and vice versa

5. The strategy is to match each patient with the

treatment most effective and suited to them
Wide variability in therapeutic response is best
explained by clinically important subtypes
The Obesities – A Plethora of Discrete Disorders

Leptin deficiency Prader- Willi syndrome Inflammatory

LepR deficiency Bardet-Biedl syndrome Diet-dependent
POMC deficiency Alström syndrome Exercise-sensitive
MC4R deficiency BFL syndrome Sleep-sensitive
aMSH deficiency Hypothalamic Insulin-induced
Sim-1 deficiency Hyperphagic Steroid-induced
PC-1 deficiency Thermogenesis deficient Progesterone-induced
KSR2 deficiency Circadian-disrupted Psychotropic-induced
MRAP2 deficiency Stress-induced Antibiotic-induced
SH2B1 deficiency Viral Endocrine disruptor
BDNF deficiency Central Phentermine-responsive
trkB deficiency Peripheral Lorcaserin-responsive
Carpenter syndrome Diffuse Topiramate-responsive
Cohen syndrome Neonatal Metformin-responsive
Ayazi syndrome Early childhood Bupropion-responsive
MOMO syndrome Peripubertal GLP-1 responsive
Rubenstein-Taybi syndrome Gestational Bypass-responsive
Fragile X syndrome Menopausal Bypass-resistant
Albright osteodystrophy “Healthy” Gastric band-responsive
Metabolic

Multiple Subtypes = Variation in Treatment Response

What Differs Among Different Obesity Subtypes

• Timing of obesity onset

• Fat location and distribution
• Metabolic consequences
• Phenotypic differences
• Hunger
• Satiety
• Reward-based eating (e.g., craving)
• Energy expenditure (thermogenesis)
• Response to environmental causes
• Dietary content
• Lack of physical activity
• Chronic stress
• Sleep deprivation
• Circadian rhythm disruption
• Response to therapies
Variations in KLF14 Gene Regulate Body Fat
Distribution in Women of European Descent

 KLF14 expression  KLF14 expression

Central adiposity Peripheral adiposity
Increased DM risk Decreased DM risk

“Apple” “Pear”

KLF14 encodes Kruppel-like factor 14, a regulator of the transcription

of multiple genes in adipose tissue

Small KS, et al., Nat Genet 2018; 50:572

Pathways of Metabolic Regulation
Pathways of Metabolic Regulation

Better Response to a Low-Carbohydrate Diet

Pathways of Metabolic Regulation

Better Response to Liraglutide

Pathways of Metabolic Regulation

Better Response to Gastric Bypass

Pathways of Metabolic Regulation
POUNDS Lost Study

• Randomized controlled trial of 4 diets

• Diets varied widely in carbohydrate, fat and protein content
• Initial intensive calorie restriction followed by “maintenance” phase
Weight Change (kg)

Time (months)

Conclusion: Nutrient content doesn’t matter – a calorie is a calorie

Sacks F et al, NEJM 2009

Wide Variation in Response to Specific Diets

Atkins Diet Zone Diet

30 30

20 20

10 10

0 0
>10% 5- 0-5% 0-5% 5- 10- 15- 20- 25- >10% 5- 0-5% 0-5% 5- 10- 15- 20- 25-
Gain 10% Gain 10% 15% 20% 25% 30% Gain 10% Gain 10% 15% 20% 25% 30%
Gain Gain

Weight Change Weight Change

LEARN Program Ornish Diet

30 30

20 20

10 10

0 0
>10% 5- 0-5% 0-5% 5- 10- 15- 20- 25- >10% 5- 0-5% 0-5% 5- 10- 15- 20- 25-
Gain 10% Gain 10% 15% 20% 25% 30% Gain 10% Gain 10% 15% 20% 25% 30%
Gain Gain
Weight Change Weight Change

Adapted from Gardner CD et al, JAMA 2007

An FGF21 Gene Polymorphism is Associated with
Differential Response to Specific Diets

rs838147 Genotype*
POUNDS Lost Study (2009)
CC
Genome-wide Association (2016) TC
TT

Low Carbohydrate Diet High Carbohydrate Diet

0 6
Time (months) 24 0 6
Time (months) 24
0 0

∆ Total Fat Mass, %

∆ Total Fat Mass, %

-1 -1

-2 -2

-3 -3

-4 -4

Same study, NEW conclusion: Dietary composition is critical

* rs838147 is a single nucleotide polymorphism in the FGF21 gene Heianza et al., Diab Care 2016
Response to a Diet is Biology Dependent

Ebbeling C, et al., JAMA, 2007

Heterogeneity of Response

Number of Subjects

Target Group

0
Weight Loss
Obesity Treatment Strategy

A Stepwise, Additive Approach

(progress through algorithm as clinically required)

Post-surgical Combinations

Weight Loss Surgery

Pharmacotherapy

Professionally-directed Lifestyle Change

Self-directed Lifestyle Change (Patient Education)

Obesity Treatment Strategy

A Stepwise, Additive Approach

(progress through algorithm as clinically required)

Professionally-directed Lifestyle Change

Self-directed Lifestyle Change (Patient Education)

Lifestyle Strategy

• Keep the goal in mind: durable weight loss

• Take a good history – assess the patient’s current lifestyle and
habits – and use it in formulating your treatment plan
• Identify greatest opportunities for lifestyle change
• Focus on changes that influence the obesity itself – do not treat only the
complications or cardiovascular risk from the obesity

• Pursue sequential application of limited (doable) lifestyle changes

• Determine effectiveness of each individual change
• Include non-diet, non-exercise interventions (sleep, stress, circadian)
• Use classic strategies of habit change (opportunity, cue, reinforcement)
• Anticipate need for the additive effects of multiple lifestyle changes

• Aim for clinically meaningful weight loss

Address Modifiable Environmental Factors

Weight Gain Circadian

Promoting Diet Activity Sleep Stress
Rhythm
Medication

• Take a good history

• Use the history to guide choice of therapy

Use Checklists

Patient Self-Assessment

❑ Diet content
❑ Eating patterns
❑ Sleep patterns and duration
❑ Daily physical activities
❑ Weight-influencing medications
❑ Chronic stressors
Medication-induced Weight Gain

Medications account for 5-10% of obesity

In each relevant category, remove or substitute

weight gain-promoting medications with weight
neutral or weight loss-promoting alternatives
Readdress Modifiable Environmental Factors

Weight Gain Circadian

Promoting Diet Activity Sleep Stress
Rhythm
Medication

Discontinue or substitute for weight gain-promoting medication

CNS Anti- Beta- Anti- Sleep

Steroids
Agents diabetes blockers histamine Aids
Readdress Modifiable Lifestyle Factors

Weight Gain Circadian

Promoting Diet Activity Sleep Stress
Rhythm
Medication

OBESOGENIC INADEQUATE
DIET SLEEP

CIRCADIAN PHYSICAL
DYSRUPTION INACTIVITY
Diets and Obesity - Summary

• Calorie restriction works for short-term weight loss

• Medical or surgical necessity
• Life events
• For long-term benefit, the chemical content of the diet is far
more important
• Reduction in metabolic and CV risk does not necessary correlate with
weight loss
• Long-term weight loss, however, has strong beneficial effects on
cardiovascular risk

• For treating obesity, each individual diet exhibits wide patient-

to-patient variation
• Different patients respond differently to different diets
• Finding the right match between diet and patient is
essential for optimal obesity care
Obesity Treatment Strategy

A Stepwise, Additive Approach

(progress through algorithm as clinically required)

Pharmacotherapy

Professionally-directed Lifestyle Change

Self-directed Lifestyle Change (Patient Education)

Medications Approved for Obesity in the U.S. – 2019

Average Mechanism of
Medication Potential Side Effects
Weight Loss* Action
Phentermine
~ 5% Adrenergic Tachycardia, hypertension
(Adipex™, Ionamin™)

Phentermine / Tachycardia, hypertension,

Topiramate 10% Adrenergic, CNS cognitive dysfunction,
(Qsymia™) neuropathy, teratogenicity
Bupropion /
CNS; opioid Seizures, confusion, anxiety,
Naltrexone 4.5%
antagonism opiate withdrawal
(Contrave™)

Lorcaserin Serotonergic
3.5% Headache
(Belviq™) (5HT2C)

Liraglutide
7% GLP-1 agonist Nausea
(Saxenda™)

Orlistat
3% Lipase inhibitor Steatorrhea, incontinence
(Xenical™)

* Beyond placebo
Other Medications that Promote Weight Loss

Medication Other Uses Mechanism Potential Side Effects

Seizures, Cognitive impairment,

Topiramate GABAergic
Migraines paresthesias, kidney stones

Bupropion Depression Dopaminergic Seizures

Opioid receptor
Naltrexone Opioid addiction Acute opioid withdrawal
antagonist
Cognitive impairment,
Zonisamide Seizures Unknown hypohidrosis,
metabolic acidosis

Metformin T2DM AMPK activation Diarrhea, metabolic acidosis

Liraglutide
Exenatide GLP-1 receptor
T2DM Nausea
Dulaglutide agonist
Semaglutide
Pramlintide T2DM Amylin agonist Nausea
Canagliflozin
Dapagliflozin T2DM SGLT-2 inhibitor Genital and urinary infections
Empagliflozin
Medications Establish a New Plateau (Set Point)

Topiramate ER + Phentermine Combination

Placebo -1.8%
Weight Change (%)

-9.3%
Topiramate ER + Phentermine - Mid dose

-10.5%
Topiramate ER + Phentermine - High dose

Time (weeks)

Garvey WT, et al. Am J Clin Nutr. 2012; 95:297-308.

Immediate Weight Regain after Treatment Cessation

Lorcaserin

Cessation vs. Continuation

Weight (kg)

Placebo

Lorcaserin
Lorcaserin

Time (weeks)

Smith SR, et al. NEJM 2010; 363:245-256

Combination Therapies Yield Improved Weight Loss

Phentermine + Topiramate
1515
Mean % weight loss at 28 weeks (28 Weeks)
Mean weight loss (%)

1010

55

00
Placebo
Placebo Phentermine Topiramate Combination
Phentermine Topiramate Combination

Aronne LJ, et al., Obesity 2013

Additive Benefits of Drug + Lifestyle Combination

Sibutramine + Lifestyle Therapy

Sibutramine
Structured lifestyle intervention
Combined therapy
(Sibutramine + structured lifestyle)
0
Weight Loss (kg)

12

16
0 3 6 10 18 40 52
Time (weeks)

Adapted from Wadden, et al., N Engl J Med 2005; 353:2111-2120

Combination Therapies Yields Improved Weight Loss

Lifestyle Therapy + Liraglutide

Run-in
Lifestyle
Therapy

6
Weight Change (kg)

Placebo
3
Placebo
0
Liraglutide
-3

-6 Liraglutide

-9
-14 -8 -2 0 26 56
Time (weeks)

Astrup A, et al., Int J Obes 2012; 36:843–854

Variable Response to Anti-obesity Medications

5% 10-20%
TBWL TBWL

Inadequate
Number of patients

response (replace)

Partially effective
(add new drug)

Highly effective

0 Weight Loss
Obesity Treatment Strategy

A Stepwise, Additive Approach

(progress through algorithm as clinically required)

Weight Loss Surgery

Pharmacotherapy

Professionally-directed Lifestyle Change

Self-directed Lifestyle Change (Patient Education)

Metabolic Surgery

Weight-independent Metabolic Benefits

Adjustable Vertical Roux-en-Y Biliopancreatic

Gastric Sleeve Gastric Diversion /
Banding Gastrectomy Bypass Duodenal Switch

Worldwide use:
8% 48% 42% 2%
Average Effectiveness of Obesity Treatments

Diabetes Prevention Program

Swedish Obesity Subjects Study

2%

13%

27%
Long-term Improved Glycated Hemoglobin

STAMPEDE Trial

Schauer PR et al., NEJM 2017

Bariatric Surgery Reduces Mortality

US Veterans Administration Experience

Arterburn D, JAMA 2015; 313:62-70

Obesity Treatment Strategy

A Stepwise, Additive Approach

(progress through algorithm as clinically required)

Post-surgical Combinations

Weight Loss Surgery

Pharmacotherapy

Professionally-directed Lifestyle Change

Self-directed Lifestyle Change (Patient Education)

Conclusions

• Although the proximal causes are diverse (lifestyle, environment,

genetics, developmental), the final common pathway for
developing obesity is a disruption of the normal regulation of
energy balance and defended fat mass
• Leading to an elevated defended fat mass (set point)

• Effective long-term treatment of obesity requires reduction of

the fat mass set point toward normal

• The complexity of the regulatory system allows for multiple

pathways of disruption, leading to MULTIPLE obesity subtypes
… with different phenotypes
… with differential responses to individual therapies

• Effective treatment – and PREVENTION – of this heterogeneous

disorder needs to address these biological considerations
Conclusions – Do’s and Don’ts of Obesity Care

DO …
• Promote a healthy diet
• High in fruits and vegetables
• High in fiber
• High in omega fatty acids
• Limited in saturated fats
• Low in processed carbohydrates
• Low in trans fats
• Promote regular physical activity
• Promote stress reduction
• Promote sleep health
• Promote normal circadian rhythms
• Encourage treatment of obesity
Conclusions – Do’s and Don’ts of Obesity Care

• DON’T …
• Expect that these changes will lead to long-term weight
loss
• They may in selected patients – if so that is a bonus

• Create expectations of weight loss when promoting

lifestyle-based reduction of metabolic risk
• Doing so is often used as a means of encouraging
patient compliance
• It is frequently counterproductive – patients who
don’t realize weight loss benefits may become
frustrated and abandon the otherwise beneficial
lifestyle recommendations
Conclusions – Do’s and Don’ts of Obesity Care

For treating obesity specifically, DO …

• Emphasize lifestyle-based anti-obesity therapies
• In all 5 domains
• Dietary manipulation
• Physical activity
• Stress reduction
• Sleep health
• Circadian rhythm normalization
• Implement them sequentially
• To enable patient compliance
• To assess their efficacy
• Include them with all anti-obesity medications
• Include them with bariatric surgery
Core Principles of Obesity Treatment

Most importantly…

Treat obesity as you would any other disease

• Match invasiveness of treatment to severity of disease

• Start with least invasive approach reasonable
• Escalate treatment as needed
• Use rational strategies and predictive models when available
• When not available, use trial and error – for non-invasive
therapies
• Use combination therapies to enhance benefit and limit risk
Practical Guidance

Go Slow and Try Different Approaches

• Test therapies sequentially
• Pursue combination therapies – including combinations of specific
lifestyle changes with more classical medical approaches
• Be supportive
• Be patient (but persistent)
• Be present

Aim for the “cure,” but always provide the care.

Lifestyle Medicine: Tools for Promoting Healthy Change

Obesity and Metabolic Risk: Different

Disorders, Different Treatments
Lee M. Kaplan, MD, PhD
Obesity, Metabolism & Nutrition Institute
Massachusetts General Hospital
Harvard Medical School

LMKaplan@partners.org

May 4, 2019
Fernando Botero, 1932-