whs pr symposium: the challenges of preventing and treating obesity

8/10/2019 WHS PR Symposium: The Challenges of Preventing and Treating Obesity

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1 st Obesity, Diabetes and Nutrition Summit

The Challenges of Preventing andTreating Obesity

Lee M. Kaplan, MD, PhDObesity, Metabolism & N trition !nstit teMassa"h setts #eneral $ospital$arvard Medi"al %"hool

LMKaplan partners.org

'omen(s $ealth %o"iety, %an ) an, P erto *i"oNovember + , - +/


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Obesity by the N mbers

Over0eight 1.%. ad lts2 3451.%. ad lts 0ith obesity2 635

1.%. "hildren 0ith obesity2 +75 8nn al 1.%. health "are e9pendit res for obesity2 : ; - billion1.%. "ons mer e9pendit res for 0eight loss prod "ts2 : ; billion

Daily deaths from obesity "ompli"ations : +,


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Disproportionate !n"rease in %evere Obesity

%t rm *, P b $ealth, - 7

Today, more than +.7 million 1% ad lts 0ith


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Compli"ations of Obesity

Psy"hologi"al

Neoplasti"

!nflammatory

%tr "t ral

Metaboli"

Degenerative 65


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Obesity is Co nterint itive

$ides in plain sight Most obesity O! re"ogni>ed by physi"ians or the p bli"

Did O! start in the past 6 years O! a problem of eating too m "h O! a single disorder

Probably several do>en or more "lini"ally meaningf l s btypes This re"ognition is essential to solving the problem

The problem is O! slo0ing do0n O! mainly in 8meri"a


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Obesity

$istori"al vie0 Lifestyle "hoi"e Chara"terologi"al fla0 A0illpo0er, psy"hologyB


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Obesity

$istori"al vie0 Lifestyle "hoi"e Chara"terologi"al fla0 A0illpo0er, psy"hologyB

C rrent perspe"tive Dysf n"tion of a "omple9 physiologi"al reg latory system ?pidemi" from "hanges in modern environment 'idely re"ogni>ed as a disease $ ge b rden of asso"iated illness Devastating effe"t on effi"a"y and ality of life


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'eight and ?nergy


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'eight and ?nergy


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8verage ad lts re ire appro9imately +6 ="alFday 8verage ad lts "ons me - G- ="alFday

8verage ad lts therefore "ons me +. G- times as m "h food asre ired

?9"ess inta=e is available for physiologi"al emergen"ies Maintaining 0eight 0ithin - lbs. bet0een ages -+ and 3

re ires mat"hing of inta=e and e9pendit re 0ithin .-5 Corresponds to a"" ra"y of /G ="alFday Less than oneGhalf potato "hip

Maintenan"e of normal fat stores Aand body 0eightB re irespre"ise disposal of / G 5 of ingested "alories daily

The Normal Physiology of ?nergy


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#! *eg lation of Metaboli" n"tion

?nergy


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The


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'eight Loss C rve

% mithran et al. N?)M - ++H 63 2+ I7G+3 /.


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# t $ormone Changes Persistently OpposeDietGind "ed 'eight Loss

% mithran et al. N?)M - ++H 63 2+ I7G+3 /.

P

J J

C C K

8 m y l i n

# h r e l

i n


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Obesity res lts from a fail re of normal 0eightand energy reg latory me"hanisms


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?nvironmental !nfl en"es on Metabolism

Dire"t !nfl en"eson


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Ma"roenvironmental !nfl en"es

-/Gho r lifestyle ?"onomi" str "t re

Time press res 'or=load Loss of do0ntime %peed of life #lobal stressors

8menable only to so"ietal intervention


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Mi"roenvironmental !nfl en"es

Types of n trients ?ating s"hed les Physi"al a"tivity %leep health Dr gs and medi"ations Lo"al stressors

8menable to individ al a"tion


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Obesity Treatment


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Overall Treatment %trategy

Typi"al 8lgorithmAprogress thro gh algorithm as "lini"ally re iredB

PostGs rgi"al Combination Therapies

'eight Loss % rgery

8dd Medi"ations

ProfessionallyGdire"ted Lifestyle Change

%elfGdire"ted Lifestyle Change


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Composition of Pop lar Diets


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Ma"ron trient Distrib tion $as Minimal ?ffe"t

at2 Lo0 A- 5B vs. high A/ 5B

Carbohydrate2 Lo0 A6 5B to high A3 5B Protein2 8verage A+ 5B vs. high A- 5B

%a"=s et al., N?)M - IH 63 24 I

Con"l sion2 No differen"e in o t"ome amongdiets of different "omposition


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Physi"al 8"tivity ?9tends 'eight Loss

Loo= 8$?8D Trial

-3minF0= 4minF0= +/IminF0= -47minF0=

Loo= 8$?8D *esear"h #ro p. Obesity - IH +727+6


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?ffe"ts of Chroni" ?9er"ise

De"reased food inta=e 8ltered food preferen"es

To0ard healthy foods

!n"reased bro0n fat development ?nhan"ed energy e9pendit re *eGreg lation of energy set point


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Lifestyle %trategy

Keep the goal in mind2 signifi"ant and d rable 0eight loss

8ssess patient(s " rrent lifestyle and habits !dentify greatest opport nities for lifestyle "hange

o" s on "hanges that infl en"e the obesogeni" environment, not the"ardiovas" lar or other ris=

P rs e se ential appli"ation of limited lifestyle "hanges Determine effe"tiveness of ea"h individ al "hange !n"l de nonGdiet, nonGe9er"ise interventions Asleep, stress, "ir"adianB

1se "lassi" strategies of habit "hange Aopport nity, " e, reinfor"ementB 8nti"ipate need for the additive effe"ts of m ltiple lifestyle "hanges

8im for "lini"ally signifi"ant 0eight loss


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Pharma"ologi"al Therapies


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Medi"ationGind "ed 'eight #ain

Medi"ations a""o nt for G+ 5 of obesity in the 1.%.

!n ea"h relevant "ategory, remove or s bstit te0eight gainGpromoting medi"ations 0ith 0eight

ne tral or 0eight lossGpromoting alternatives


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'eight Loss from Other Medi"ations

Medi"ation !ndi"ated 1ses Comments

< propion Depression 8void in bipolar disease

Topiramate%ei> resMigraines

Mood disordersMay prod "e ne rologi"al sideeffe"ts

onisamide%ei> res

Mood disorderse0 st dies

MetforminType - diabetes

PCO% *are liver to9i"ity

Liragl tide. ?9enatide Type - diabetes !n e"table

Pramlintide Type - diabetes !n e"tableH na sea "ommon

Canagliflo>in Type - diabetes

%trategy2 8im for Do ble


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Optimal Pharma"ologi"al %trategy

Optimi>e the patient(s " rrent medi"al regimen 8void 0eight gainGpromoting medi"ations % bstit te a more 0eightGfriendly alternative

Personali>e the "are2 find the best treatment for ea"h patient P rs e se ential trials of different medi"ations Minim m threshold for longGterm se2 5 0eight loss < ild to -G6 dr g "ombinations as needed

8im for s bstantial Anot minimally importantB 0eight loss 1se in "on n"tion 0ith ongoing lifestyleGbased therapy

8nti"ipate lifeGlong se of s ""essf l regimens


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$eight oss &aries $idely "mong 'atients

8dapted from $ansen DL et al ., !)O - +H - 2/I3

*esponder Tail

%ib tramineGind "ed 'eight Loss


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56PraderG 'illi syndrome


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'hat Differs 8mong Different Obesity % btypes

X Timing of obesity onsetX at lo"ation and distrib tionX Metaboli" "onse en"esX Phenotypi" differen"es

X $ nger X %atietyX *e0ardGbased eatingX ?nergy e9pendit re

X *esponse to environmental "a ses

X ?atingX ?9er"iseX %tressX %leep deprivationX Cir"adian disr ption

X *esponse to therapies


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'eight Loss

N m

b e r o f

% b e "

t s

$eterogeneity of *esponse

$ighlyresponsives bgro p


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8lgorithm ?9ample + OffGLabel 1se

Phentermine+ G6 mgFd to "lini"al effe"t

TopiramateA- G- mgFd to "lini"al effe"tB

(nade)uate $eight oss inimum "de)uate $eight oss

"dd*

Topiramate

A- G- mgFd to "lini"al effe"tB

PhentermineMetforminA+ G6 mgFd to "lini"al effe"tB

"dd*

< propion

onisamide

Naltre9one%e"ond agent

Liragl tide

"dd*


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8lgorithm ?9ample - 8pproved 1se

Phentermine+ G6 mgFd to "lini"al effe"t

(nade)uate $eight oss inimum "de)uate $eight oss

symia

AtopiramateFphentermineBAes"alate to "lini"al effe"tB Phentermine

Lor"aserinAes"alate to "lini"al effe"tB

"dd*

Orlistat


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% rgi"al Therapies


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'eight Loss % rgery

#astri" Combination

8d stable#astri"


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Metaboli" % rgery

8d stable#astri"


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8verage ?ffe"tiveness of Obesity Treatments

%0edish Obesity % b e"tsDiabetes Prevention Program


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% rgery De"reases LongGterm Mortality

+ 4 gastri" bypass patients and mat"hed "ontrols 7.+ year mean follo0G p #astri" bypass gro p e9hibited overall / 5 red "tion

in mortality %pe"ifi"G"a se mortality after gastri" bypass

35 red "tion from C8D I-5 red "tion from type - diabetes 3 5 red "tion from "an"er

1tah %t dy

8dams et al., N#+ - 7


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#ly"ated $emoglobin


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#ly"ated $emoglobin 8d sted by


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'hy is bariatri" s rgery so effe"tiveY

h i f i i %


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Me"hanisms of


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The effe"ts of bariatri" s rgery are f ndamentallyand broadly different from the effe"ts of other

types of 0eight loss

#! ? d " i * *J#


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#! ?ndo"rine *esponses to *J#e the obesity

Meas re and follo0 0eight and


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?mbra"e Modest 'eight Loss C rrent nonGs rgi"al 0eight loss therapies are generally

an ad3uvant treatment for obesity "omorbidities o" s on 0hat is a"hievable and s stainable

1nderstand that there are biologi"al limits to ea"h therapy


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#o %lo0 and Try Different 8pproa"hes Test therapies se entially P rs e "ombination therapies in"l ding "ombinations of spe"ifi"

lifestyle "hanges 0ith more "lassi"al medi"al approa"hes


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Parting Tho ght Obesity Prevention

The lessons from the development of effe"tiveobesity therapies 0ill be the best g ide for moreeffe"tive obesity prevention strategies, in"l ding2

*e"ognition of m ltiple, differing "a ses of obesity ?9pe"tation that different approa"hes 0ill benefit different

s bpop lations

The same need for m ltiple, varied and "ombinatorialapproa"hes as for obesity treatment

1 st Obesity Diabetes and Nutrition Summit


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1 st Obesity, Diabetes and Nutrition Summit

The Challenges of Preventing andTreating ObesityLee M. Kaplan, MD, PhDObesity, Metabolism & N trition !nstit teMassa"h setts #eneral $ospital$arvard Medi"al %"hool

LMKaplan partners.org

'omen(s $ealth %o"iety, %an ) an, P erto *i"oNovember + , - +/

whs pr symposium: the challenges of preventing and treating obesity

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