2025+iCARDIO联盟肥胖管理全球实施指南：聚焦心血管代谢疾病的预防与治疗（英文版））

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GLOBALCARDIOLOGY
GlobalCardiology2025;3:181-206
DOI:10.4081/cardio.2025.86
GUIDELINES
iCARDIOAllianceGlobalImplementaonGuidelines
fortheManagementofObesity2025
FocusonPrevenonandTreatmentofCardiometabolicDisease
StefanD.Anker(Germany),LinongJi(China),TammyKindel(USA),AndrewJ.S.Coats(Australia),DikeOjji
(Nigeria),AdrianaPuenteBarragán(Mexico),PeterRossing(Denmark),ShelleyZieroth(Canada),ShaafAhmad
(USA),ShariqUsman(USA),GeetaAppannah(Malaysia),AlisonL.Bailey(USA),AhmedBennis(Morocco),
AndreaBrandao(Brazil),JavedButler(USA),MelanieJ.Davies(UK),LubomiraFabryova(Slovakia),Yuan-Lin
Guo(China),HidetakaItoh(Japan),UdayM.Jadhav(India),CarelW.LeRoux(UK),FaustoJ.Pinto(Portugal),
JulioRosenstock(USA),BanshiSaboo(India),HaniSabbour(UAE),MangeshTiwaskar(India),KarolE.Watson
(USA),KwangWeiTham(Singapore),FernandoStuardoWyss(Guatemala),WalterP.Abhayaratna(Australia),
WilliamT.Abraham(USA),WaelAlMahmeed(UAE),AlessiaArgirò(Italy),JohnJ.Atherton(Australia),Danielle
Belardo(USA),RaquelCampuzano(Spain),NandiniChaerjee(India),VijayChopra(India),Marc-AndréCornier
(USA),SarahDavies(UK),ClemenciadeRuedaPanadero(Spain),AnastaseDzudie(Cameroon),TyJ.Gluckman
(USA),MuhammadShahzebKhan(USA),KamleshKhun(UK),YuriLopan(Russia),ZhiyiMa(China),
OkechukwuS.Ogah(Nigeria),AbrahamOomman(India),EmilioS.PeraltaLopez(Honduras),PingLi(China),
PaulPoirier(Canada),JulieRedfern(Australia),GiuseppeM.C.Rosano(Italy),AmitSaraf(India),SamehShaheen
#
(Egypt),SubodhVerma(Canada),StephanvonHaehling(Germany),YuhuiZhang(China),MarthaGula(USA),
##
NaveedSaar(UK),JoseLuisZamorano(Spain)
Drs.Anker,JiandKindelwouldliketobeconsideredjoint?rstauthors.
#
Drs.Gula,SaarandZamoranowouldliketobeconsideredjointseniorauthors.
Note:Allauthorswereeitherwringtaskforcemembersoracveguidelinereviewers.Theauthora?liaonsarelistedattheendofthedocument.
Abstract
Thereareanumberofguidelinesonhowtomanageobesity,butinconsistenciesinhealthcareaccess,varyinginfra-
structure,resourceconstraintsanddiverselocalpracticesrestricttheirglobalapplicability.Thisunderscorestheneed
foruniversalrecommendationsthataddresstheuniquechallengesfacedbypatientsandhealthcareprovidersworld-
wide.OurGlobalGuidelinesemphasizetheincorporationofnoveltherapies,whileintegratingstandardsofcarewith
themostup-to-dateevidencetoenableclinicianstooptimizeobesitymanagement.Context-specificrecommendations
tailoredtoindividualpatientneedsarehighlighted,providingathoroughevaluationoftherisks,benefits,andoverall
valueofeachtherapy,aimingtoestablishastandardofcarethatimprovespatientoutcomesandreducestheburden
ofhospitalizationinthissusceptiblepopulation.TheseGlobalGuidelinesprovideevidence-basedrecommendations
thatrepresentagroupconsensusconsideringthemanyotherpublishedguidelinesthathavereviewedmanyofthe
issuesdiscussedhere,buttheyalsomakenewrecommendationswherenewevidencehasrecentlyemerged,and–
mostimportantly–alsoproviderecommendationsonseveralissueswhereresourcelimitationsmayputconstraintson
thecareprovidedtopatientslivingwithobesity.Such“economicadjustment”recommendationsaimtoguidesituations
when“Resourcesaresomewhatlimited”orwhen“Resourcesareseverelylimited”.Hence,thisdocumentpresentsa
comprehensiveupdatetoobesitymanagementguidelines,therebyaimingtoprovideaunifiedstrategyforthephar-
macological,non-pharmacological,andinvasivemanagementofthissignificantglobalhealthchallengethatisapplicable
totheneedsofhealthcarearoundtheglobe.
?2025TheAuthors.GlobalCardiologyispublishedbyPAGEPressPublicaons.
ThisisanopenaccessarcleunderthetermsoftheCreaveCommonsAribuonNonCommercialInternaonalLicense(CCBYNC4.0),whichpermitsanynoncommercial
use,distribuon,andreproduconinanymedium,providedtheoriginalauthor(s)andsourcearecredited.Nocommercialuseofanypartofthisdocument,inanylanguage,
isallowedwithoutwrienpermission,whichcanbeobtaineduponsubmissionofawrienrequesttotheChiefExternalA?airs&EducaonO?cerofTranslaonalMedicine
Academy,whichisthepartyauthorizedtohandlesuchpermissionsonbehalfoftheiCARDIOAlliance(E-mail:[e-mail]).titititititititititititititititititititititititititttititititititititititttitititititititititititititititttititititititi
182S.D.Ankeretal.
Keywords:guidelines;obesity;cardiometabolicdisease;CARDIOAlliance.
Received:16September2025Accepted:24September2025.
Correspondenceto:StefanD.Anker,MDPhD,DepartmentofCardiology(CVK),CharitéCampusCVK,AugustenburgerPlatz1,D-13353Berlin,Germany.
E-mail:[e-mail]
Preamble
arewrienbyateamincludingworld-renownedexpertswith
TheInternaonalCARDIOAlliancetoImproveDiseaseOut-
comes(iCARDIOAlliance:hps://icardioalliance.org)aimstoamaximumof50%ofthewringtaskforcerepresenngEu-
ropeandNorthAmericaand50%ormorefromtherestofthe
gatherleadingcardiovascularsocieesaroundtheglobeas
partnerorganizaonstoimprovethequalityofcardiovascularworld.Thepeerreviewteamisalsomadeupofglobalexperts
care,fromprevenonanddiagnosistotreatmentandfollow-furtherenrichingthesedocumentsandleadingtoa?nalphase
up.Thegoaloftheseglobalimplementaonguidelinesistoofpublicreviewopentoall.Furthermore,weimplementapub-
achieveglobalrepresentaoninwringpanelsandtoproducelicreviewprocessforallourguidelinedocuments.Inthisway,
conciseandpraccalguidelinesapplicabletoallcardiovasculartheviewpointsofmanypersonswithlivedexperienceareem-
careworldwide.Inaddiontoclinicalpracceguidelinesde-beddedwithinthisglobalimplementaonguidelineprocess.All
velopedbyothermedicalassociaons,therecommendaonsguidelinedocumentsarepublishedinseveraljournalsandopen
byiCARDIOAlliancetakeintoaccountresourceavailabilityonaccess.ThroughthisinnovaveapproachiCARDIOAlliance
atleast3economiclevels(withnoeconomicconsideraon;hopestoenhanceguidelinedisseminaonandimplementaon
resourcessomewhatlimited;resourcesseverelylimited).Theyonaglobalscale.
Introducon
8
overallhealthcare-relatedspending.Theeconomicimpactof
Obesityisachronic,relapsingdiseasecharacterizedbyabnor-
overweightandobesityin2019isesmatedbecirca2.2%of
malorexcessiveadiposessueaccumulaonthatimpairs,
globalgrossdomescproduct,onaveragerangingfrom20
amongstotherconsequences,physical,metabolic,andpsy-
chosocialhealth.Itisde?nedbytheWorldHealthOrganiza-USDpercapitainAfricato872USDpercapitaintheAmericas
2
on(WHO)asabodymassindex(BMI)≥30kg/mor27.5andfrom6USDinlow-incomecountriesto1,110USDinhigh-
9
21
incomecountries.Thisunderscorestheimportanceofade-
kg/mforAsianpopulaons.Itemergedasanepidemicinthe
2
quaterecognionofapproachesforearlydetecon,lifestyle
U.S.inthelate1970s,beforesubsequentlysweepingacross
3
therestoftheworld.Recently,therewasagrowingdebatemodi?caons-basedmanagement,drugtherapies,andsurgi-
onthepotenallimitaonsoftheroleofBMIinclassifyingcalmodaliesquintessenaltodealingwiththeperilsofrap-
idlyincreasingprevalenceofobesity.
obesity,asittendstoover-andunder-esmateadiposity,but
The?rstcomprehensivesetofobesity-relatedguidelineswas
moreresearchisneededtode?nebestpragmacwaysto?nd
peopleatmostrisk.Inthenear-term,BMIwillsllbeaverypublishedin1998bytheNaonalHeart,Lung,andBloodInsti-
7
important–andinmostcases–theleadingparametertoas-tute(NHLBI).Sincethen,adiverseassortmentofguidelines,
sesspresenceofobesityfastandsimple.Theterm‘clinicalprincipallyfromthedevelopedworld,hasbeenpublishedinthe
10-28
literature.However,heterogeneityinthepopulaonpool
obesity’referstothepresenceofexcessadipositythatisas-
sociatedwithfunconalimpairmentorincreasedriskofcar-usedfordevisingtheserecommendaonsleadingtopoorgen-
diometabolic,physical,orpsychologicalcomplicaons,eralizability,varyingcomplexiesinhealthcareinfrastructure
4,5
regardlessofBMI.RecentdatafromtheGlobalBurdenofacrossinstuons,aperceivedlackofknowledgeamongst
DiseaseStudy2023esmatethatover1billionindividualsprovidersandalimitedavailabilityofresourcesespeciallypreva-
29
globallyarenowlivingwithobesity(504millionadultwomen,lentinthedevelopingworld,havebeenrecognizedasconsid-
374millionadultmen,and159millionchildrenandadoles-erableimpedimentsintheiruniversaladoponandapplicaon
6
cents),re?ecngadramacriseoverthepastthreedecades.forobesitydiagnosisandmanagement.
Thisstaggering?gureunderscoresthegrowingpublichealthThelastfewdecadeshaverecordedarapidevoluoninobe-
sitymanagement,throughabeerunderstandingoftheim-
challengeposedbyobesityacrossagegroupsandgeographic
7
regions.Cawleyetal.concludedthatintheU.S.alone,thepactoflifestyle-basedintervenons,advancementsin
obesity-relatedhealthcareexpenditureamountedtoabouttherapeucopons,andminimallyinvasivebariatricsurgery
$260billionin2016,constungbetween5%and10%ofopons.Theclinicalpracceguidelines(CPGs)havefailedto
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iCARDIOAllianceGlobalImplementationGuidelinesfortheManagementofObesity2025183
keeppacewiththischanginglandscapeofobesitymanage-Weacknowledgethattherewasuncertainty,whethertouse
ment,underscoringtheneedforanewandup-to-datesetoftheterm“peoplewithobesity”or“paentswithobesity”.In
recommendaons.Inaddion,avastmajorityoftheexisngthisdocument,wewillmostlyuse“paentswithobesity”,as
recommendaonsarederivedfromCPGspublishedinotherthisismorecommonlyusedglobally.Tomakethedocument
disciplinesthatmenonobesityonlyverybrie?y,underlining
morereadableandconcise,wedecidedtonotreferenceeach
apaucityofcomprehensiveconsensusstatementsonobesityrecommendaonwhentheevidenceiswidelyknownandal-
managementfrominternaonalcommieesonobesityand
readyrepeatedlyreferencedinotherguidelines.Whenrec-
cardio-metabolichealth.Finally,theprevalenceofobesityisommendaonsweremade,alsomorerecentpublished
30
increasinginbothhighandlow-middleincomecountries,
evidencewastakenintoaccount,forinstanceregardingGLP-
highlighngtheurgentneedforsuccessfuladaptaonofrec-
1RA-basedtherapies.
ommendaonstobemorerelevanttoandimplementablein
low-incomecountriesasasteptowardscurtailingthegrowth
Diagnosis
intheobesityepidemic.
Intervenonalrandomizedcontrolledtrialsoverthepasttwo
Bodymassindex(BMI)isthemostwidelyusedtoolfordiag-
yearshaveshownthattargengobesityasanindependent
nosingobesity.Duetoitssimpliscnature,itfailstoprovidea
riskfactorinbothpeoplewithandwithoutdiabetesmigates
moregranularesmateoftotalbodycomposion,akeymet-
theriskofcardiovascularadverseevents,includingatheroscle-
ricforcalculangobesity-associatedcardiometabolicrisk.
roccardiovasculardisease,heartfailurehospitalizaons,and
Moreover,theinterracialphenotypicvariaonsinstatureand
33
chronickidneydisease,aswellasMASHandobstrucvesleep
bodyfatdistribuonarenotaccountedforbyBMI.Alterna-
31,32
apnea.
vemeasureofadiposityhavebeenproposed,includingwaist
Hence,thisstatementaimstoestablishanup-to-datesetof
circumference.Acomprehensiveaccountofobesity-related
CPGsfordiagnosingandtreangobesityacrossawidespec-
diagnoscmodaliesislistedinTable1.
trumofhealthcaresengs,includingbothopmaltreatment
strategies,aswellasalternavestrategiesinresource-limited
Non-judgmentallanguage
sengs(inbothdevelopedcountriesanddevelopingcoun-
tries).Theseguidelinesweredraedinconsultaonwithex-
Individualslivingwithobesityexperiencediscriminatorybe-
perts,independentreviewers,andmembersofthegeneral
haviorsandscrunyduetoexcessbodyweight,aphenome-
34
public.
nontermed‘weightsgma’.Researchhasshownthatthe
internalizaonofweightsgmaisassociatedwithsigni?cantly
35
worseweightlossoutcomessecondarytoalackofcon?-
dence,anxiety,depression,andareducedsenseofself-es-
Methods
36
teem.Healthcareworkersshouldascertaintheextentofthe
paent’swillingnesstodiscussweightmanagement,askopen-
Theseconsensus-basedclinicalpracceguidelinesfordiag-
endedquesons,andusenon-judgmentallanguageduringpa-
nosingandmanagingobesityweredevelopedpertheestab-
entencounters(e.g.replacingphrasessuchas,‘obese
lishedmethodologyforbestpraccesinguideline
individuals’or‘morbidobesity’with‘individualswithobesity’
development.Asystemacreviewofexisngliteraturewas
resultsinbeerdiscussionoutcomes).
conductedtoestablisharepositoryofpublishedguidelinedoc-
The5Asframework(ask,assess,advise,agree,andassist)pro-
umentsandconsensusstatements,usingthefollowingsearch
videsthefoundaonforiniangandconducngmovaonal
strategy:(obesityORoverweightOR?bodymassindex?OR
interviewingforweightmanagementinindividualslivingwith
BMI)AND(guidelineOR?clinicalpracceguideline?OR?prac-
37
obesity.
ceguideline?OR?consensus?OR?consensusstatement?).
Aerdiscussionamongstexperts,themostrelevantguidelines
Bodymassindexandanthropometricmeasures
foreachregionwereselectedandtheirrecommendaons
werecompiled.Followingthis,redundant/similarrecommen-
2
daonswereeliminated.Bodymassindex(BMI),calculatedasweight/height(re-
2
portedinkg/m),isauseful?rst-linescreeningtoolforidenti-
Theremainingrecommendaonswerereviewedbythecom-
miee,andoverseveraliteraons,outdatedandnon-pernentfyingpaentswithobesity.ThestandardBMIcut-o?sfor
overweightandobesityrecommendedbytheWorldHealth
recommendaonswereeliminated.Newrecommendaons
22
wereaddedbasedonemergingdata,thatwerenotavailableOrganizaon(WHO)are25-29.9kg/mand≥30.0kg/m,re-
specvely.Despiteitswidespreadadopon,BMIislimitedin
whensourceguidelinesweredraed.Basedontheavailable
evidenceandconsensusamongthecommieemembersre-itsabilitytodiscernleanbodymassfrombodyfat,thuspro-
gardingtherisksandbene?tsofintervenons,therecommen-vidingapooresmaonofthetotalbodyfatpercentage-an
daonswereclassi?edintofourers:stronglyrecommendedimportantclinicalmarkerforobesity-relatedcardiovascular
38
(SR),recommended(R),suggested(Su),anddonotdo(DND)disease(CVD)riskprognosis.BMIfailstoadjustforage,sex,
(Table1).Lastly,whereverrelevant,alternaverecommenda-andrace-baseddi?erencesinbodyfatcomposion,especially
onswereaddedforlowresourcesengs.inadults.Wangetal.demonstratedthatAsiansrecorded
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184S.D.Ankeretal.
highertotalbodyfatpercentagesatlowerBMIvaluesthan
Lifestylemodi?caons
39
theirCaucasiancounterparts.

Anthropometricmeasurementsnamely,higherwaistcircum-
Lifestyle-basedinterventionshaveuntilrecentlyconstituted
ference(males:≥102cm[40inches];females:≥88cm[35
thecornerstoneofobesitymanagementtoimprovehealth.
inches]withlowercut-o?sforAsianmen[390cm]andwomen
Itisanumbrellaphraseencompassingadiversearrayofnon-
[380cm])andhigherwaist-to-hiprao(normallimits:<0.90
pharmacologicalinterventionsthatinvolveinducingasus-
40
formales;<0.85forfemales),orhigherwaist-to-heightrao
tainedchangeinhabitspertainingmainlytodietandphysical
41,42
(≥0.50)indicateincreasedcardiometabolicrisk.DEXAand
activityforriskfactormodificationandimprovedsurvival
computedtomography(CT)scansprovidemorecomprehen-
outcomes.Theyarerecommendedasthefirst-linetreatment
sivemeasuresofbodyfatdistribuon.CombiningBMIwith
modalityasastandalonetherapyorinconjunctionwith
anthropometricmeasuresofcentralobesity,whichhave
48
pharmacological/surgicalinterventions.Implementing
demonstratedsuperiorsensivityandspeci?cityinCVDrisk
high-frequencycounseling(≥16sessionsin6months)focus-
prognoscaon,allowsforamorerobustevaluaonofobe-
ingonnutritionalchanges,physicalactivity,andbehavioral
sity-relatedcomplicaons.Todate,however,BMIremainsthe
strategiescanhelpachievelong-termenergydeficitgoals.
primaryobesitymetricusedinmanycountries,andmore
Ourgroup’srecommendationsforlifestylemodification-
workisneededtodetermineifothermeasurescanaidclinical
basedinterventionstargetedatweightlossandmaintenance
pracceandimproveoutcomes.
arelistedinTable2andTable3.


BMIevaluaonforindividualsofAsiandescent
Dietaryinterventions


Foragivenlevelofbodyfat,age,andsex,individualsofAsian
Calorie-restrictionthroughdietaryregulationcanachievea
descentgenerallyexhibitalowerBMI(byapproximately2-3
net-negativeenergybalancerequiredfortriggeringweight
2
kg/m)comparedtotheirWhitecounterparts,likelyaribut-
lossbutmayalsobeassociatedwithincreasesinhunger.En-
abletovariaonsinbodycomposionandmuscularity,man-
ergyintakereductionof500-750Kcalperdaycanmanifest
dangtheneedforusingdi?erentBMIcut-o?sforthiscohort
inaninitialweightlossof0.5-1.0kg(1.0-2.2lbs)perweek,
43
forseverityandriskesmaon.
or2-3kg(4.4-6.6lbs)amonth,notaccountingforinterper-
In2004,aWHOExpertConsultaonpanelanalyzedmetabolic
49
sonalvariability.Weightlossdoesnotcontinueindefinitely
riskdatafromAsiancountriesandrecommendedlowering
despitecontinuouscalorierestriction.
BMIthresholdsforpublichealthintervenonsinAsianpopu-
TheMediterraneanDiet(MD)inspiredbytraditionaleating
laons.Theyproposedde?ningBMIrangesof23.0-27.5kg/m2
habitsinMediterraneancountries,emphasizesplant-based
21
asoverweightandBMI≥27.5kg/masobeseforthissubset.
foods(fruits,vegetables,legumes,wholegrains,nuts,and
However,itisimportanttoacknowledgethatdi?erentAsian
extravirginoliveoil),moderateintakeoffishanddairy,and
countriesmayhaveestablishedtheirownBMIcut-o?sforthe
limitedconsumptionofredmeat.Itisdeemedasmostef-
diagnosisofoverweightandobesitybasedonlocalepidemi-
50
fectiveatnotonlyinducingweightloss,butatmaintaining
ologicaldata.Wheresuchcountry-speci?cthresholdsexist,
5-10%weightlossoverprolongedperiods,withorwithout
theyshouldbeusedinplaceofthegeneralizedWHOrecom-
51
physicalactivity.Poulimeneasandcolleaguesrecruitedpar-
mendaonstoensurecontextuallyappropriateriskstra?ca-
ticipantsfromtheMedWeightstudyandadherencetoMD
onandintervenon.Usingthestandardcut-o?sinthe
wasassessedamongthem.Thestudyreportedthatthepar-
UnitedStates,AsianAmericanshavelowratesof
ticipantsadherenttotheMDweretwo-timesmorelikelyto
overweight/obesitycomparedtotheNon-HispanicWhite(NH-
maintainweightlossof5-10%thantheirnon-adherentcoun-
White),AfricanAmerican,andHispanicethnicgroups,yetthey
51
terparts.
su?erfromadisproporonatelyhighburdenoftype2dia-
Thedietaryapproachestostophypertension(DASH)diethas
betesandassociatedmetabolicabnormaliesdespitenormal
44
demonstratedefficacyininducingandmaintainingweight
bodyweightpro?les.
lossaswell,andisrecommendedasoneofthefirst-linein-

terventionsforindividualswithobesitysufferingfromhyper-
Bioelectricalimpedanceanalysis(BIA)forbodyfat
tension.Ameta-analysisunderscoredanadditional-1.4kg
esmaon
weightlossamongthecohortconsumingtheDASHdietover

52
otherlow-energydiets.
BIAulizesimpedancetoelectricconduconasasurrogatefor
45
IntermittentFasting(IF)dietsentailalternatingbetween12-
esmangtotalbodyfatpercentageandfat-freemass.The
20hourslongperiodsoffastingandunrestrictedeating.The
accuracyandprecisionofthisapproximaonarea?ectedby
46
16:8method(fasting16hoursadayfollowedbyan8-hour
hydraonstatus,bodygeometry,andbodywaterdistribuon.
Themostaccuratemethodsforesmangtotalbodyfatper-eatingwindow)andfastingfor24hourstwiceaweek(the
5:2method)aresomeofthemostcommonlyadoptedap-
centagearedensitometry-basedmodalies,namely,under-
47
waterplethysmographyandDEXAscanning.However,noneproachesfordieterspracticingIF.Inameta-analysiscon-
53
ofthesemorecostlymeasuresareripeforwidespreaduse.ductedbyAlmabrukandcolleagues,theIFfastinggroup
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iCARDIOAllianceGlobalImplementationGuidelinesfortheManagementofObesity2025185
experiencedweightreductionsrangingfrom2to6kg,andtotheindividual’spreferences,culturalcontext,andlifestyle,
2
BMIdecreasedbetween1and4kg/mover1.5andsixandthatsupportslong-termadherence.Notably,thelimited
months,respectively.long-termsuccessofmostdietsislessoftenduetothespe-
High-protein(HP)dietsincludeconsuming≥1.6gofproteincificmacronutrientcompositionorstructureofthedietitself,
perkgofbodyweightorobtaining≥25%ofcaloriesfromandmorecommonlyattributabletochallengeswithsus-
54
protein.tainedadherenceovertime.
Low-fat(LF)dietsprescribederivinglessthan30%ofdaily
calorierequirementfromfats.EvidenceonusingLF-dietsasPhysicalactivity
55
astandalonetherapyforweightlossissparse.Astrupetal.
reportedameanweightlossof3.2kg(95%CI:1.9-4.5kg)inPhysicalactivityconstitutesthesecondmostimportant
theLF-dietgroupcomparedtothecontrolintheirmeta-lifestyleinterventiondirectedatinducingaweightlossof5-
56
analysisof16RCTs.Onthecontrary,theDIRECTtrialcom-10%.While,dietremainstheprimarydriverofweightloss,
paringlow-carbohydrate,Mediterranean,andLFdietsasmostindividualsdonotachievesubstantialorsustained
reportedhigherweightlossinthelow-carbohydrateandweightreductionthroughexercisealone,physicalactivity,in
Mediterraneangroups(-4.7kgand-4.4kg,respectively).Theparticularresistancetraining,hasbeenshowntobuildand
5761
PREDIMEDtrialdemonstratedbettercardiovascularout-preserveleanmusclemassdespiteenergyrestriction.Fat-
comesinthegroupontheMediterraneandietsupple-freemasspreservationhasbeenshowntomaintainahigher
mentedwithextra-virginoliveoilornutscomparedtotherestingmetabolicrate,improvestrengthandaerobiccapac-
LF-dietgroup.ity,especiallyinolderadultswithobesity,andsafeguard
62
Low-carbdiets(LCDs)andcalorie-restricteddiets(CRDs):againstsarcopenia.Thedurationofexercisetrainingand
Low-carbdietsarefurtherclassi?edintoverylow,low,mod-weightlossthroughvisceralfatreductionexhibitadose-re-
63
erate,orhigh-carbdietsbasedonperdiemcarbohydrateloadsponserelationship.Althoughthereexistsagreatdealof
(verylow;20-50g/day,low;≤130g/day).Ketogenicdietsareheterogeneityintheliterature,withregardtotheduration
atypeofverylow-carbdiet.Theyworkbydeplengtheofphysicalactivityperweek,thegeneralconsensusisthat
body’sglycogenstorestousefatstoresastheprimarysourceforpatientswithobesity,≥150minutesofexercisetraining
11
forenergyproduconthroughthegeneraonofketones.Al-aweekisassociatedwithweightlossinductionandmain-
thoughe?ecveatinducingweightlossandimprovingtenance,inadditiontoheraldinganimprovementincardio-
glycemiccontrolindiabecs,theLCDshavebeenlinkedtovascularoutcomesinthelongrun,althoughareductionin
58
greateroddsofcardiovascularmorbidityandmortality.cardiovascularmortalityhasnotbeenshown.Accordingto
Thus,warranngcauonandcarefulpaentseleconwhentheAmericanCollegeofSportsMedicine,150-225minand
idenfyingcandidatesforLCD-basedweightlossintervenon.225-400minofaerobicexerciseperweekwereassociated
Calorie-restricteddietsareaneffectiverecourseforachiev-with2to3kgand5to7.5kgofweightloss,respectively,al-
ing5-10%weightloss.Combinedwithincreasedproportionsthoughlong-termmaintenancebeyond3yearsremainsa
64
ofproteinanddairyintake,theymayreducebodyfatper-challenge.
65
centage,totalcholesterol(TC),andlow-densitylipoprotein-Willisetal.concludedthataerobictrainingdemonstrated
cholesterol(LDL-c)levels.However,statinsremaintheamoresignificantdecreaseintotalbodyfatcontentthanre-
mainstayofpharmacologictherapyforloweringLDL-cinpa-sistancetraining.Theyalsodemonstratedthatcombiningre-
tientswithobesityduetotheirrobustevidenceinreducingsistancetrainingwithaerobicexercisedidnotleadto
atheroscleroticcardiovascularrisk.Intermittentfastinghasincrementalweightloss.
gainedtractionasapotentmeansforachievingcaloriere-ItmaybehelpfultoconsidertheMetabolicEquivalentof
striction.Inarandomizedcontrolledtrial(RCT),Sunandcol-Task(MET)valuesofcommonaerobicactivities.Forexample,
leaguesuncoveredthesynergisticweightlosseffectachievedbriskwalkingtypicallyrangesfrom3.5to4.5METs,cycling
bycombiningLCDswithCRDs.Comparedtothoseintheatamoderatepaceyields4to7METs,andjoggingorrunning
calorie-restricted(CR)onlygroup,participantsintheLCDrangesfrom7to12METs,dependingonspeedandincline.
59
plusCRgrouplost55%morebodymassindex(BMI).Theseestimatescanhelpcliniciansrecommendactivitylev-
60
Wycherlyetal.performedameta-analysisof95studies,elsthatalignwiththepatient’scapacityandgoals.
whereintheyestablishedmodestdecreasesinbodyweightPhysicalactivityisastrongpredictoroflong-termweightloss
(-0.79kg;95%CI,-1.50to-0.08)andbodyfatmass(-0.87kg;maintenance,independentofdietandcaloricrestriction.The
95%CI,-1.26to-0.48kg)inthegroupconsumingHPdietsinNationalWeightControlRegistry(NWCR)recommends60
comparisontothelow-fat,low-carbohydrate,energy-minutesofmoderate-intensityexerciseperdayforlong-term
66
restrictedstandardproteindietgroup.weightlossmaintenance.
67
Inconclusion,thisconsensusstatementrecognizesthatthereInanRCTconductedbyJakicicandcolleagues,275min/
isnouniversallysuperiordietarystrategyforthemanage-weekofphysicalactivitywhencombinedwithrestricted
mentofobesityandthattheaverageeffectsaremodest.caloricintakewasfoundtobeassociatedwiththehighest
Rather,theoptimaldietaryapproachisonethatistailoredoddsoflong-termweightlossmaintenanceof5-10%.
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186S.D.Ankeretal.
timeofpublishingthisguideline,oralsemaglutidewasnot
Pharmacologicaltreatment
yetapprovedbyanyregulatoryauthorities,andhenceitcan-

notberecommended.Higherdose(7.2mg)onceweekly
Recommendaonspertainingtoopmalpharmacotherapeu-
semaglutidemayalsobecomeavailableinthenearfuture,
cintervenonsforobesitymanagementarelistedinTable4
buttheyarenotyetapprovedforuse.
aswellasinFigure1andFigure2.
SemaglutideTreatmentEffectinPeoplewithobesity(STEP)

wasthefirstglobalprogramtoevaluatesemaglutide2.4mg
Glucagon-likepeptide(GLP)-1receptoranddual
onceweeklyforweightmanagement.
agonists
77
STEP1TheSTEP1trial(SemaglutideTreatmentEffectin

Peoplewithobesity)wasthefirstlarge-scale,double-blind,
Inthelastdecade,incretin-basedmedicationswithhighef-
randomizedcontrolledstudytodemonstratethatonce-
ficiencyofweightlosshaveemerged.Theseincludeliraglu-
weeklysubcutaneoussemaglutide2.4mgledtosignificant
tide,semaglutide,andtirzepatide.TheyactonGLP-1
weightlossinnon-diabeticadultswithoverweightorobesity.
receptorsinthepancreaticβ-cells,increasingintracellular
Participantsreceivingsemaglutidelostanaverageof14.9%
cyclicAMP(cAMP)andtriggeringendogenousinsulinrelease
ofbodyweight,comparedto2.4%intheplacebogroupover
andappetitesuppression.TirzepatideisadualGLP-1RA/
68weeks.
Glucose-dependentinsulinotropicpolypeptide(GIP)agonist
78
STEP2comparedsemaglutide2.4mgvs1.0mgwith
thatworksbymodulatinginsulinreleaseandincreasing
placebo.The2.4mgdosecohorthadthehighest9.6%of
adiponectinlevels.
baselinebodyweightlosscomparedtothe1.0mggroupthat

experienced7%ofbaselinebodyweightloss.
Liraglutide
79
STEP3showedthatincludingintensivelifestyletherapy

withsemaglutidedidnotaffectweightlossastheweightloss
Liraglutide,aGLP-1receptoragonist(RA)isapprovedfor
2
inthedrugplusintensivelifestylearmwas16%,thesameas
chronicweightmanagementinadultswithaBMIof30kg/m
2
STEP1,whichdidnothaveanintensivelifestylecomponent.
oratleast27kg/m,ifatleastoneweight-relatedcomorbid
80
STEP4revealedthatdiscontinuingsemaglutideresultedin
conditionispresent.Dosingbeginsat0.6mgdailyforone
weightregain,whilecontinuingsemaglutidebeyond20
weekandisthentitratedupweeklyat0.6mgintervalsuntil
68
weeksresultedin16-18%weightloss.
therecommendeddoseof3mgdailyisreached.LEADER,
81
STEP5wasthefirstlong-termstudythatranfor104weeks
SatietyandClinicalAdiposity-LiraglutideEvidenceinindivid-
69
andcorroboratedthefindingsofthepreviousstudies,and
ualswithandwithoutdiabetes(SCALE),SCALEMainte-
707172
showedhowincreaseddurationoftreatmentresultedin
nance,SCALEDiabetes,andSCALESleepApneawere
maintenanceofthe16%weightlossachievedat1year.No
amongthemostprominentRCTsevaluatingliraglutide’s
73
weightregainwasobservedwhenthemedicationwascon-
safetyandefficacyprofiles.Ameta-analysisrevealedthat
tinued.
liraglutideproducedamean5.2kgplacebo-subtracted
82
STEP8,aphase3trial,comparedonce-weeklysubcuta-
weightlossat1year,with63%ofparticipantsachievinga
neoussemaglutide(2.4mg)withonce-dailyliraglutide
≥5%weightloss,inclusiveof34%ofparticipantswholost
(3.0mg)inadultswithoverweightorobesitywithoutdia-
≥10%ofinitialweight.Weightlossof7%wasmaintainedfor
74
betesmellitus.Semaglutideresultedinsignificantlygreater
3yearsintheSCALEPrediabetesstudy.
weightloss(-15.8%)comparedtoliraglutide(-6.4%).
Therecentexpirationofliraglutide’spatentprotectionin
Semaglutidealsoshowedhigheroddsofachieving≥10%,
multiplecountriesopensthedoorforgenericversions,
≥15%,and≥20%weightloss.Bothtreatmentshadsimilar
whichmaybecomeacost-effectiveGLP-1RAoptionin
resource-limitedsettings.Thiscouldenablebroaderphar-ratesofgastrointestinaladverseevents.
83
macologicimplementation,particularlyinLMICswhereIntheSTEP9trial,semaglutide2.4mgadministeredonce
weeklyresultedinsignificantimprovementsinkneepain,
neweragentslikesemaglutideandtirzepatideremaincost-
function,andstiffness,aswellasweightloss,inindividuals
prohibitive.
withobesityandsymptomatickneeosteoarthritis.These
Semaglutidefindingssuggestthatsemaglutidemayhaveaddedmuscu-
loskeletalbenefits,particularlyinpatientsforwhomjoint
painlimitsmobilityorexercisetolerance.
Semaglutide,anotherGLP-1RA,worksbyup-regulatingthe
7584
downstreameffectsofGLP-1receptoractivation.Once-TherecentlyconcludedSTEPUPtrialcomparedweekly7.2
weeklysubcutaneoussemaglutide1.0mgwasapprovedbymgsemaglutideto2.4mgsemaglutideandplaceboinadults
theFDAin2017andtheEuropeanMedicinesAssociationinwithobesitywithoutdiabetesmellitus.Peopletreatedwith
76
semaglutide7.2mgachievedasuperiorweightlossof20.7%
2018forthetreatmentoftype2diabetes.In2021,theFDA
approved2.4mgonceweeklysemaglutidefortreatingobe-after72weekscomparedtoareductionof17.5%with
sityinadults.Ongoingtrialsoforalsemaglutidemayresultsemaglutide2.4mgand2.4%withplacebo.Inaddition,
inanotheroptionforthetreatmentofobesity,butatthe33.2%ofthosewhoreceivedsemaglutide7.2mgachieved
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aweightlossof25%ormoreafter72weeks,comparedtogreatermedianimprovementfrombaseline(estimatedtreat-
16.7%withsemaglutide2.4mgand0.0%withplacebo.Inmentratio:1.13;95%CI:1.06-1.21;p=0.0004).Italsore-
85
theSTEPUPT2Dtrialresultswerelargelyconfirmedinducedthecompositeriskofrescuetherapyorall-cause
adultswithobesitywithdiabetesmellitususingthesamedeathby54%(HR0.46;95%CI:0.24-0.85),andimproved
treatmentapproach.Peopletreatedwithsemaglutide7.2qualityoflife.
93
mgachievedasuperiorweightlossof13.2%after72weeksTheESSENCEtrialenrolledadultswithmetabolicdysfunc-
comparedtoareductionof3.9%withplacebo(p<0.0001).tion-associatedsteatohepatitis(MASH)andmoderatetoad-
Inpatientswithsemaglutide2.4mg,weightlossamountedvancedfibrosis(stage2-3).Treatmentwithweekly
to10.4%.semaglutide2.4mgfor72weeksachievedresolutionof
Inallthesetrials,weightlossesweregenerallylessinpeoplesteatohepatitiswithnoworseningoffibrosisin~62.9%vs
withtype2diabetesthanwithout,thoughrecentevidence~34.3%withplacebo,andimprovementinfibrosiswithno
suggeststhatweightlossesaresubstantiallygreaterintypeworseningofsteatohepatitisin~36.8%vs~22.4%.Patients
86
2diabeteswhenHbA1clevelsarelower.Thelowerweightalsolostanaverageof~10.5%ofbodyweightvs~2.0%with
lossesseenwithweightlosstherapiesathigherHbA1clevelsplacebo,withasafetyprofileconsistentwithpriorsemaglu-
maybepartlyduetocorrectionofunintentionalweighttideobesitytrials.
lossesduetoglucosuria.InSURMOUNT-2,weightlossesin
inpeoplewithtype2diabeteswassimilartothatinpeopleTirzepatide
87
withoutwhenHbA1c<7.0%.
88
TheSELECTstudyshowedweightmaintenancefor4yearsIntheSURPASS1-5trials,whichevaluatedglycemiclowering
withoutanyregain,providedthemedicationwascontinued.efficiencyasanprimaryendpoint,differentdosagesof
ThisisalsotheonlyRCTinpatientswithobesitywithoutdi-tirzepatide(5mg,10mg,and15mgonceweekly)demon-
abetesthathasshownareductioninmajoradversecardio-stratedsignificantweightreductionasasecondaryendpoint
vasculareventswhenanintentionalweightlossstrategywasinpatientswithtype2diabetesmellitus(T2DM),especially
8894
used.whencomparedtoplacebo(SURPASS1),semaglutide1mg
95
(SURPASS2),insulindegludecasanadd-ontometformin
96
CardiovascularstudieswithsemaglutidewithorwithoutSGLT2inhibitor(SURPASS3),insul-
97
inglargine(SURPASS4),andplacebo+insulinglargine(SUR-
8898
TheSELECTtrialwasalarge,randomized,placebo-con-PASS5).Theoverallweightlossrangedfrom7.6kg,10.7
trolledcardiovascularoutcomestrial(CVOT)thatenrolledkg,to12.9kgwithtirzepatide5mg,10mg,and15mg,re-
17,604patientswithestablishedatheroscleroticcardiovas-spectively.
culardisease(ASCVD)andeitherobesityoroverweight(BMITheSURMOUNT1-4trialswerespecificallydesignedtoeval-
2
≥27kg/m)butwithoutdiabetes.Overameanfollow-upofuatetheweight-loweringeffectivenessandsafetyof
39.8months,subcutaneoussemaglutide2.4mgonceweeklytirzepatideasanadjuncttolifestyleinterventionscompared
significantlyreducedtheincidenceofmajoradversecardio-toaplaceboinpatientswithobesity,withorwithoutT2DM.
99
vascularevents(MACE),acompositeofcardiovasculardeath,SURMOUNT1comparedtirzepatide5mgvs10mgvs15
nonfatalmyocardialinfarction,ornonfatalstroke,by20%mgvsplaceboinpatientswithoutdiabetes.Attheendof72
comparedtoplacebo(HR0.80;95%CI,0.72-0.90;p<0.001).weeks,5mg,10mg,and15mggroupsexperienceda-15%,
Althoughhazardratiosforcardiovasculardeath(HR0.85;-19.5%,and-20.9%weightreductionvs-3.1%inthosere-
95%CI,0.71-1.01)andthecompositeofcardiovasculardeathceivingplacebo.Inthe3-yearextensionofSURMOUNT-1
orheartfailureevents(HR0.82;95%CI,0.71-0.96)favoredamongparticipantswithprediabetes,meanweightreduc-
semaglutide,theseendpointsdidnotmeettherequiredsig-tionsat176weekswere-12.3%withtirzepatide5mg,-
nificancethresholdsinhierarchicaltesting.18.7%with10mg,and-19.7%with15mg,comparedwith
8990100
STEPHFpEFandSTEPHFpEFDMshowedthattreatment-1.3%intheplacebogroup.
87
withsemaglutideledtoareductioninheartfailureevents,SURMOUNT2includedpatientswithconcomitantobesity
NT-proBNPandCRPlevels,aswellasanimprovementin6-andtype2diabetesmellitus.tirzepatide10mg,15mg,and
minutewalkingdistance(6MWD)andKansasCityCardiomy-placebowerecomparedfor72weeks.Themeanchangein
opathy(KCCQ)scoresinpatientswithconfirmedHFpEFandbodyweightattheendwas-12.8%,-14.7%,and-3.2%,re-
theobesityphenotype,overoneyear,comparedtospectively.
91101
placebo.SURMOUNT3patientsweresubjectedtoanintensive
92
STRIDE,aphase3brandomizedplacebo-controlledtrial,lifestyleintervention,andonlythosewholost35%weighton
studyingtheroleofsemaglutideinperipheralarterydiseaseitwererandomizedtoeithertirzepatide(10or15mg)or
(PAD)reportedthatinpatientswithconcomitantdiabetesplacebo.Meanweightchangeattheendof72weekswas-
andPADwithintermittentclaudication,semaglutide(1.0mg18.4%fortirzepatide,whilethegrouptreatedwiththein-
weekly)significantlyimprovedmaximumwalkingdistanceattensivelifestyleinterventionandplacebohadaweight
52weeksbyameanof39.9metersversusplacebo,a13%increaseof2.5%.
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102107
SURMOUNT4startedasanopen-labeltrial.ParticipantsIntheSURPASS-CVOTtrial,inmorethan13,000patients
experienceda20.9%weightloss.Thentheywererandom-withT2DM,weeklysubcutaneoustirzepatide(upto15mg)
ized.Thosewhoswitchedtotheplaceboexperienceda14%ascomparedtoweeklydulaglutide(1.5mg)wasnon-infe-
weightgain,whereasthosewhocontinuedwithtirzepatideriorforrateofmajoradversecardiovascularevents(MACE-
lostanadditional5.5%oftheirinitialweight.3:hazardratio0.92,95.3%CI:0.83-1.01,p=0.086)andwas
103
SURMOUNT5trialdemonstratedthatmaximallytoler-foundtonominallylowerall-causemortalityby16%
atedtirzepatide(10?mgor15?mgonceweekly)achievedsig-(p=0.002).Atthetimeofpublication,thetrialwasnotyet
nificantlygreaterweightlossthanmaximallytoleratedpublished.
semaglutide(1.7mgor2.4mg)over72weeksinadultswith
obesityoroverweightandatleastonecomorbidity.Specif-Resource-limitedsettings
ically,tirzepatideledtoa20.2?%meanreductioninbody
weightvs13.7%withsemaglutide(p<0.001),alongwithaConsiderusingbiosimilarliraglutide,whichisexpectedto
greatermeandeclineinwaistcircumference(-18.4?cmvs-belessexpensivethansemaglutideortirzepatideinre-
13.0?cm).source-limitedsettings.Hopefully,inafewyears,biosimilar
ForpatientswhoplateauonGLP-1receptoragonists,semaglutidemaybecomeavailable,aswellasmultiple
switchingtoanalternativeGLP-1RAbaseddrugcouldoffersmall-moleculenon-peptideGLP-1RAscurrentlyindevelop-
additionalbenefitintermsofweightloss.Thisstatementment,whichmaybeeasiertoproduceinamorescalable
reflectsaconsensusopinionbasedonavailablecomparativefashion,makingthemmoreaffordable.Unfortunately,com-
trialdataandclinicalexperience.However,itisimportantpoundedproductsofGLP-1RAsofunknownoriginarebeing
tonotethatnodedicatedrandomized?switch?studycur-increasinglyusedaslower-costalternativesinsomecoun-
rentlyexiststoformallyevaluatethisstrategy.Untilfurthertries,despitealackofdataonmanufacturingqualitycontrol
studiesareavailable,suchanapproachshouldbeconsid-andtheabsenceofrandomizedcontrolledtrialstoproperly
eredcautiously,consideringsafety,patientpreference,assesstheirsafetyandefficacy.
andlong-termgoals.Drugaccessibility,safety,andlong-Theauthorsofthisguidelinerecognizetheneedtoaddress
termadherenceremainadditionalcriticalfactorsintherapyaccesstoobesitymedicationsinlower-andmiddle-income
selection.countries.However,inmanypartsoftheworld,thesein-
104
SURMOUNT-OSAinvestigatedtheutilityoftirzepatideincretin-relatedcompoundedmedicationsareeitherdisal-
patientsintwocohorts(Cohort1notusingCPAP,Cohort2lowedorillegal,oraresubjecttolitigationincourts,asthey
usingCPAP)withobstructivesleepapnea(OSA).Theyfoundareassociatedwithsignificantsafetyandefficacyconcerns.
thatamongpersonswithmoderate-to-severeobstructiveWecannotrecommendtheuseofthesecompoundedobe-
sleepapneaandobesity,tirzepatidereducedtheAHI,bodysitymedications,butrecognizethefactthattheyareare-
weight,hypoxicburden,high-sensitivityC-reactiveproteinflectionofaseriouscalltothepharmaceuticalindustryto
(hsCRP)concentration,andsystolicbloodpressureandim-addresstheneedtoimproveaccessandaffordabilityto
provedsleep-relatedpatient-reportedoutcomes.largerpopulationsofthecurrentlyapproved,properly
105
SYNERGY-NASHrevealedthatinpatientswithMASHandtestedobesitydrugs.
moderateorseverefibrosis,treatmentwithtirzepatidefor
52weekswasmoreeffectivethanplacebowithrespecttoCost-effectivenessandaccessconsiderations
theresolutionofMASHwithoutworseningoffibrosis.inpharmacologictherapy

CardiovascularstudieswithtirzepatideWhenselectinganti-obesitypharmacologicagents,bothef-
ficacyandcost-effectivenessmustbeconsidered.While
106
IntheSUMMITtrial,weeklysubcutaneoustirzepatide(upGLP-1RAsdemonstratethegreatestweightlossbenefits,
to15mg)wascomparedwithplaceboover104weeksintheyarealsoamongthemostexpensiveoptions,withan-
adultswithobesityandheartfailurewithpreservedejectionnualcostssignificantlyhigherthanagentslikeorlistator
fraction(HFpEF;LVEF≥50%).Tirzepatidereducedtheriskofphentermine/topiramate.Economicanalysessuggestthat
cardiovasculardeathorworseningheartfailureeventsbyforpopulationswithestablishedcardiovasculardiseaseor
38%comparedtoplacebo(HR0.62;95%CI,0.41-0.95;diabetes,semaglutidemaybecost-effectiveduetoassoci-
p=0.026),andimprovedpatient-reportedsymptomburdenatedreductioninadverseevents.Incontrast,orlistatand
andqualityoflife.MeanKansasCityCardiomyopathyQues-naltrexone/bupropionmayoffermorefavorablecost-bene-
tionnaireClinicalSummaryScoresincreasedby19.5pointsfitprofilesforprimaryobesitymanagementinlower-income
comparedto12.7withplacebo(meandifference6.9;95%settings.However,fororlistatandnaltrexone/bupropionas
CI,3.3-10.6;p<0.001).Thesefindingssupporttirzepatide’swellasforphentermine/topiramatenocardiovascularout-
emergingroleasapotentialdisease-modifyingtherapyforcomebenefithasbeendocumented.
obesity-relatedcardiovascularcomorbidities.Additionally,coldchainstorage,injectabledeliveryroutes,
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andlimiteddrugapprovalsincertaincountriesfurthercon-notbeenelucidated,itishypothesizedtoreducetotalbody
113114
strainaccessibility.Healthsystemsshouldevaluateallthesefatcontent.TheEQUIP-trialshowedasignificantde-
issueswhenselectingpharmacologicalinterventions.creaseinbodyweight(10.9%ofbaselineweight)inthe
groupreceivingPhentermine/Topiramate(15mg/92mg)
SGLT2inhibitorswhencomparedtomatchedcontrolsreceivingplacebo
(1.6%ofbaselineweight).Phentermine/TopiramateisFDA
SGLT2inhibitorsarenotapprovedtotreatobesityperse,
approvedforuseasaweightlossregimenintheU.S.since
i.e.theyarenotdrugsfortreatment“ofobesity”.However,2012.Itisalsoapprovedinmorethan10Europeancoun-
theyareveryeffectivemedicinesforpatients“withobesity”tries;howeveraEurope-widegeneralapprovalofEMAhas
andcardio-renal-metabolicdisease.SGLT2inhibitorsworknotbeengranted.Thiscombinationiscontraindicatedinpa-
byblockingthere-uptakeofsodiumandglucoseintheprox-
tientswithawithglaucoma,andinhyperthyroidism.
imalconvolutedtubule-amechanismthatisthoughttoun-
derlieitsweightlosseffects.Althoughtheycauseminimal
Naltrexone/Bupropion
weightlossandarenotconsideredweightlossagentsper
se,theyareveryeffectiveinimprovingoutcomesinchronic
Naltrexone/Bupropioninduceweightlossbyincreasingsig-
conditionsthatcommonlyco-existwithobesity,including
nalingfromthepro-opiomelanocortin(POMC)neuronsin
heartfailureandchronickidneydisease.Mazidiandcol-
thehypothalamus.Consequentlydecreasingappetiteby
81
leagues,intheirmeta-analysisof43RCTsevaluatingthe
bluntingthehyperphagiapathwaysinthemesolimbicsys-
115
efficacyandsafetyprofileofSGLT2inhibitorsinmanagingtem.Therecommendeddoseforobesitytreatmentisa
116
diabetes-relatedcomorbidities,reportedaweightedmean
totalof32mgnaltrexoneand360mgbupropion.The
differenceof-1.8kg(95%CI:-2.1to-1.6kg)betweenthe
ContraveObesityResearchprogramencompassesaseries
117118119
SGLT2inhibitorgroupandthosereceivingplacebo.Ina
offourRCTs(COR-I,COR-II,COR-DMandCOR-
120
meta-analysisof15randomizedcontrolledtrials,UsmanandBMOD)thatformthecentralbodyofliteraturedepicting
108
colleaguesdemonstratedthatSGLT2inhibitorssignifi-theefficacyofthenaltrexone/bupropioncombinationdrug
cantlyreducedrisksforHF-relatedhospitalizationandcar-
inobesitymanagement.Thesephase?IIItrialsdemonstrated
diovascularmortalityinpatientswithHF,type2diabetes,
thatoverapproximately56weeks,naltrexone32?mg/bupro-
chronickidneydisease,andatheroscleroticcardiovascularpion360?mgpluslifestyleinterventionledtomeanweight
disease.lossof8.1-8.2%inCOR-IandCOR-II(vs1.3-1.7%with
placebo),3.7%inCOR-DM(vs1.7%),and9.3%inCOR-
Orlistat
BMODwithintensivebehavioralmodification(vs5.1%).A
historyofhypertension,depression,breastfeedingoractive
Orlistatworksbyinhibitingthelipasemediatedbreakdownsubstanceabuseprecludestheuseofnaltrexone/bupro-
121
offats,thusdecreasingfattyuptakefromthegut.Oneofpion.
theearliestinvestigationsofOrlistat-mediatedweightloss
109
wasconductedbyZavoral,whoperformedapooled
Lisdexamfetamine
analysisofdatafromfiveRCTsandreportedthatattheone
yearmark,patientstakingorlistat120mgthricedaily,ex-Astimulantmedicationusedveryrarelyfortreatingobesity
periencedsignificantlygreaterweightlossthanthoseona
inchildrenandadolescentswithunderlyingeatingdisor-
placebo,withanaveragereductionof9.2%comparedto
ders.ItisprimarilyapprovedforADHSandbingeeating.To
5.8%(p<0.001).Additionally,ahigherpercentageoforlis-avoidadverseeffects(e.g.,significantweightgaininasmall
tat-treatedpatientsachievedweightlossofover5%andsubgroupofpatients),closefollow-upisneededwhenthis
over10%oftheirinitialbodyweight,comparedtothoseontreatmentisapplied.
placebo(69.6%vs51.9%;p<0.001and42.1%vs22.7%;
110-112
p<0.001,respectively).Sincethen,severalRCTsandThefutureofanti-obesitydrug-basedtherapy
prospectiveobservationalstudieshavedetailedmorecom-
prehensiveaccountsoforlistat’sefficacyinmanagingSeveralnoveldualandtripleagonistsbuiltonaGLP-1RA
obesityandpreventingthedevelopmentofaswellastreat-backboneareinvariousstagesofclinicaltrials.Inthephase
122
ingitsco-morbiditiesnamely,dyslipidemias,MASLDandIIIREDEFINE?1trial,weeklyCagriSema(combinationof
diabetes.amylin-basedcagrilintideandincretin-basedsemaglutide)
(2.4?mgeach)producedameanweightlossof20.4?%
Phentermine/Topiramatevs3.0?%withplaceboat68weeks(difference-17.3percent-
agepoints;p<0.001).Infullyadherentparticipants,weight
Phentermine,anadrenergicstimulant,inducesweightlosslossreached22.7%,withover40%achieving≥25%reduc-
byappetitesuppression.Althoughtheexactmechanismstioninbodyweight.Orforglipron,aonce-dailyoralnonpep-
underlyingTopiramate’sroleininducingweightlosshavetideGLP-1RA,demonstratedaplacebo-adjustedweight
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190S.D.Ankeretal.
reductionofupto5.9%andHbA1creductionofupto1.07%sophagealrefluxdisease(GERD)andBarrett’sesophagus,
123130
over40weeksinthephase3ACHIEVE-1trial.Noveldrugandtheirreversiblenatureoftheprocedure.
therapiesactingcentrally(setmelanotide;melanocortin4
[MC4]receptoractivator,velneperit;neuropeptideYantag-Intragastricballoon(IGB)andbanding
onist,zonisamide-bupropion;combinationdrugcomprised
132
ofsodiumandT-typecalciumchannelblockeraswellasAbuDayyehetal.conductedanRCTtodemonstratethat;
norepinephrine-dopaminereuptakeinhibitor,andcannabi-whenusedinconjunconwithlifestyleintervenons,ad-
noidtype-1receptorblockers),andperipherallyincludingjustableIGBresultedinsigni?cantweightloss(15%intheaIGB
amylinmimetics(davalintide),pramlintide-metreleptingroupvs3%inthecontrolgroup;p<0.0001)whichmaintained
(amylinandleptinanaloguesworkingbyslowinggastric
for6monthsfollowingballoonremoval.Mostotherstudies
emptyingandinducingearlysatiety),beloranib(methionine
suggestedweightregainwhentheballoonisremoved.
aminopeptidase2inhibitors),andnovelanti-obesityvac-
Gastricbandingulizeslaparoscopicapproachtomodulate
cines(ghrelin,somatostatin,adenovirus36)arecurrently
gastric?lling.Theoverallweightlosse?ectisachievedbyin-
underinvestigationasemergingadjunctsinobesityphar-
vokingtheearlysaetymechanisms.Thereareanumberof
124
macotherapy.
wellconductedRCTsshowingthesafetyandsuperiore?cacy

ofgastricbandingincomparisontolifestylechanges.Theonly

long-termRCTcomparingRoux-en-Ygastricbypasswithgastric
Bariatricsurgery
bandingreportedsigni?cantlysuperiorweightlossoutcomes
132

fortheformer.
125
Sinceitsinception,circa70yearsago,bariatricsurgery

hasbecomeaneffectivetreatmentoptionforpatientswith
BiliopancreacDiversionwithDuodenalSwitch
obesity,especiallyinthepresenceofcomplicationssuchas
(BPD/DS)
diabetesmellitus,metabolicsyndrome,andmetabolicdys-

function-associatedsteatoticliverdisease(MASLD).The
TheBPD/DSisanothere?ecvebariatricsurgeryprocedure,
126
BRAVEtrialrandomizedindividualswithMetabolicDys-
characterizedbyasleevegastrectomyfollowedbygastroileal
134
function-AssociatedSteatohepatitis(MASH)tolifestyle
andileoilealanastomoses.Inalongitudinalanalysisofthe
modificationsplusbestmedicalcaregrouporabariatricsur-
weightlosse?ectsofthisprocedurebySorribasandcol-
gerygroup.Thetrialconcludedthatbariatric-metabolicsur-
leaguesreported15%,18%and18%inialbodyweightloss
geryismoreeffectivethanlifestyleinterventionsand135
at2,5and10yearintervals.Inameta-analysisesmang
optimizedmedicaltherapyinthetreatmentofMASH.
thee?cacyofbariatricsurgeryprocedures,Buchwaldetal.,
Roux-en-Ygastricbypass,sleevegastrectomy,endoscopicin-
reportedthatthepercentageofextrabodyweightlost(calcu-
tragastricballoon,biliopancreaticdiversion,andgastric
latedas[preoperaveBMI?currentBMI)/(preoperave
bandingareamongtheroutinelyofferedoptionsforpa-
BMI?25]×100)at2-yearsoffollow-upwasthehighest(73%)
tientsconsideringundergoingbariatricsurgeryforachieving
fortheBPD/DSsubgroup,followedbythegastricbypass
11
weightlossgoals.Recommendationspertainingtotheuse
(63%),gastroplasty(56%),andgastricbanding(49%)sub-
ofbariatricsurgeryasatreatmentmodalityforobesityare136
groups.
listedinTable4.



Roux-en-Ygastricbypass
Consideraonsregardingspecial

populaons
Thisisthemostwidelyadoptedtechniqueforperforming

bariatricsurgeryowingtoitssuperiorsafetyandefficacypro-
127
Childrenandyoungadolescents
file.Mechanismsarecomplex-amongstotherthingsitin-

ducesweightlossbyincreasingsignalingfromtheguttothe
AforecasngstudyfromtheGlobalBurdenofDiseaseStudy
brain,includinghamperingghrelinrelease,increasingsatiety
6
128
2021examinedtheprevalence,trends,andfutureprojecons
hormones,bileacidsandalteringthegutmicrobiota.It
ofoverweightandobesityinchildrenandadolescentsacross
shouldespeciallybeconsideredinpatientswithBMI≥30
2
kg/m(orhigher)withdiabetesmellitus,hypertension,hy-180countriesfrom1990to2021,withprojeconsextending
129
to2050.Thestudyreportedthatbetween1990and2021,the
perlipidemiaorotherCVDriskfactors(Table5).
globalprevalenceofoverweightandobesityinyouthdoubled,

whileobesityalonetripled.In2021,anesmated93.1million
Sleevegastrectomy
children(5-14years)and80.6millionadolescents(15-24
Sleevegastrectomyiseffectiveandcomparabletoslightlyyears)werelivingwithobesity.Thehighestprevalencewas
worseforweightloss,incomparisontotheRoux-en-Yby-notedinNorthAfrica,theMiddleEast,andpartsofOceania,
130,131
pass,butwithagreaterriskofdevelopinggastroe-withthegreatestincreasesobservedinSoutheastAsia,East
GlobalCardiology2025
10.4081/cardio.2025.86titititititititititititittititititititititititititititititititititititititititittitititititititititititititititititititititttititifttitititititttititititititi
iCARDIOAllianceGlobalImplementationGuidelinesfortheManagementofObesity2025191
144,148
Asia,andOceania.By2050,obesityratesareexpectedtorisewhereappropriate.Allobesitymedicaons,including
further,parcularlyinSouthAsia,surpassinghistoricaltrendsGLP-1receptoragonistsofanykind,orlistatandphenter-
globally.Rounescreeningforoverweightandobesityshouldmine/topiramateetc.,arecontraindicatedduringpregnancy,
beginatage6years,usingBMI-for-agepercenlesbasedonandwomenofreproducveageonsuchtherapiesshouldre-
WHOorCDCgrowthcharts.Earlierscreeningmaybewar-ceivecounselingoncontraceponandmedicaondisconn-
143,144,148,149
rantedinchildrenwithriskfactorssuchasafamilyhistoryofuaonifpregnancyoccurs(Table7).
obesity,rapidweightgainininfancy,orcomorbidcondions
137
suchassleep-disorderedbreathingorinsulinresistance.AsObesityandpsychiatricillnesse
withadults,e?ecveweightmanagementinchildrenandado-
lescentsrequiresmorethandietarychangesalone;itshouldRecommendaonspertainingtointervenonsforobesityin
includephysicalacvityandpsychosocialsupport,withdietarypaentswithpsychiatricillnessesarelistedinTable8.
strategiestailoredtothechild’spreferences,comorbidies,
foodrestricons,andpersonalcontextaspartofacompre-
138
hensivecareplan.Emergingroleofar?cialintelligence
School-basedintervenonssuchashealthiermealo?erings,inobesity
physicalacvityprograms,andculturallyrelevantnutrion
awarenesstalkscanhelpfosterhealthierhabitsatayoungageAr?cialintelligenceandmachinelearningtoolsarebeingin-
andpreventobesity,especiallyinresource-limitedsengscreasinglyulizedduetotheirgrowingulityindetecngearly
withlimitedhealthcareaccess.obesity-relatedcomorbidityrisks,creangindividualizedtreat-
150,151
RecentevidencesupportstheuseofGLP-1RAsinchildrenandmentplans,andmonitoring.Theabilityofmachine-learn-
adolescentswithobesity.Inchildrenaged6to<12years,li-ing(ML)algorithmstoanalyzelargedepositsofmulmodal
raglude3.0mgdailyreducedBMIby7.3%at52weeks(vsdataabstractedfromelectronichealthrecords(EHRs)enables
139
1.5%withplacebo).Amongadolescents,semaglude2.4theiden?caonofpaentsathighriskandcanevenanci-
150
mgweeklyachieveda16.1%BMIreduconat68weeks(vspatetreatmentresponse.
140
0.6%),andliraglude3.0mgdailyreducedBMIby4.6%atThiscanespeciallybeusefulinresource-limitedsengswhere
141
56weeks(vsa1.6%increase).Thesetrialssupportthead-targetedintervenoninat-riskpaentscanhelpalleviatethe
juncveuseofGLP-1RAswithlifestyletherapyinpediatrichighobesity-relatedcomorbidityandmortalityburden.
obesity(Table6).
PregnantfemalesConclusions
Thedetrimentalimpactofgestaonalobesityonbothmater-Thisglobalconsensusdocumentprovidesanintegrated,evi-
nalandfetalwell-beinghasbeenwelldocumentedinthelit-dence-basedframeworkforthediagnosisandmanagementof
erature,makingadequateweightcontrolbothintheantenatalobesity,forimplementaonacrossdiversehealthcaresystems.
periodandduringpregnancyofparamountimportance.Aho-Toensurerelevanceacrossglobalcontexts,theguidelinesfea-
liscapproachconsisngofnutrionalsupport,physicalac-turescalableintervenons,includinglifestyleandbehavioral
vityguidance,andsupervisioncanopmizeobesitystrategies,aswellas?exiblepathwaysfortheincorporaonof
managementduringpregnancy,improvinghealthoutcomespharmacologicandsurgicaltherapieswherefeasible.Recent
138
forboththefetusandthemother.therapeucadvances,suchasGLP-1receptoragonistsanddual
Thedetrimentalimpactofgestaonalobesityonbothmater-GIP/GLP-1agents,holdsubstanalpromise,butconcerns
nalandfetalwell-beinghasbeenwelldocumentedinthelit-arounda?ordability,accessibility,andregulatorystatusrepre-
erature,makingadequateweightcontrolbothinthesentamajorhurdleinglobaladoponofthesetherapies.
antenatalperiodandduringpregnancyofparamountimpor-Thewringcommieeo?ersfeasiblealternavesaertaking
tance.Aholiscapproachconsisngofnutrionalsupport,intoaccounttheindividuallevelvariabilityincomorbidies,
physicalacvityguidance,andsupervisioncanopmizeobe-healthstatus,culturalbeliefs,healthcareaccessandadher-
152
sitymanagementduringpregnancy,improvinghealthout-encebarriers,andthesocialdeterminantsofhealth.Clinical
comesforboththefetusandthemother.Balancedjudgmentformsthecornerstoneofadapngrecommenda-
dietaryintakeinlinewithgestaonalcalorierequirementsre-onstothecircumstancesofeachpaent,especiallyinre-
mainskey.Restricveorvery-low-caloriedietsarestronglysource-constrainedenvironments.
142-145
discouraged.Moderate-intensityphysicalacvity,suchUlmately,theseguidelinesaimnotonlytosupportevidence-
asbriskwalkingorswimming,isgenerallysafeandencour-basedpraccebutalsotoadvanceequity,feasibility,andcon-
agedintheabsenceofcontraindicaonsandhasbeenshowntextualsensivityinobesitycareacrossawiderangeofhealth
142,146,147
tobeassociatedwithbeeroutcomes.Earlyscreen-systems.Giventherapidlychangingevidencebase,weanc-
ingforgestaonaldiabetesshouldbeo?eredtoallpregnantipateupdangtheseguidelineswithin2years,withafocused
individualswithobesity,withrepeattesngat24to28weeksupdateinbetween.
GlobalCardiology2025
10.4081/cardio.2025.86
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194














































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196S.D.Ankeretal.







Figure1.Treatmentprinciplesforobesity.
Figure2.Weightlossmedicationrecommendationchartforobesityinadults.
GlobalCardiology2025
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titttitititttitttitititititititititititttititititititititttitttititititi
iCARDIOAllianceGlobalImplementationGuidelinesfortheManagementofObesity2025201
ConsultantinCardiologyattheDepartmentofCardiologyand
Con?ictofInterest
CardiacCT,MGMNewBombayHospital,Mumbai,India;Carel
W.LeRoux,DiabetesComplicaonsResearchCentre,Univer-
SeeAppendix.
sityCollegeDublin,Ireland;DiabetesResearchCentre,Ulster
University,UK;FaustoJ.Pinto,CentroAcademicodeMedicina
deLisboa,CCUL@RISE,FaculdadedeMedicinadaUniversi-
Acknowledgements
dadedeLisboa,Lisbon,Portugal;JulioRosenstock,Velocity
ClinicalResearchatMedicalCity,Dallas,TX,USA;Banshi
TheworktowardsthisdocumentissupportedbyTranslaonal
Saboo,Diacare-DiabetesCareAndHormoneClinic,Ahmed-
152
MedicineAcademy,aswellasbytheiCARDIOAllianceand
abad,India;HaniSabbour,CardiologyDepartment,Mediclinic
theiCARDIOAlliancePartnerSociees(hps://icardioal-
AirportRoadHospital,AbuDhabi,UnitedArabEmirates;
liance.org/partnersociees/).
MangeshTiwaskar,ConsultantPhysicianandDiabetologist,
ShilpaMedicalResearchCentre,Mumbai,Maharashtra,India;
KarolE.Watson,DavidGe?enSchoolofMedicineatUniver-
AuthorInformaon
sityofCalifornia,LosAngeles,CA,USA;KwangWeiTham,De-
partmentofEndocrinology,WoodlandsHealth,Naonal
TaskForceMemberA?liaons:
HealthcareGroup,Singapore;FernandoStuardoWyss,
StefanD.Anker,DepartmentofCardiology(CVK)ofGerman
GuatemalaCardiovascularServicesandTechnology,
HeartCenterCharité;GermanCentreforCardiovascularRe-
GuatemalaCity,Guatemala
search(DZHK)partnersiteBerlin,CharitéUniversit?tsmedizin,
Berlin,Germany;LinongJi,DepartmentofEndocrinologyand
ReviewerA?liaons:
Metabolism,PekingUniversityPeople’sHospital,Beijing,
WalterP.Abhayaratna,SchoolofMedicineandPsychology,The
China;TammyKindel,MedicalCollegeofWisconsin,Milwau-
AustralianNaonalUniversity,Canberra,Australia;WilliamT.
kee,WI,USA;AndrewJ.S.Coats,HeartResearchInstute,
Abraham,DivisionofCardiovascularMedicineandTheDavis
Sydney,Australia;DikeOjji,DepartmentofInternalMedicine,
HeartandVascularResearchInstute,TheOhioStateUniversity
FacultyofClinicalSciences,UniversityofAbuja,Nigeria;Adri-
(OSU)CollegeofMedicineandOSUWexnerMedicalCenter,
anaPuenteBarragán,CentroMedicoNacional20deNoviem-
Columbus,OH,USA;WaelAlMahmeed,Heart,Vascularand
bre,ISSSTE,MexicoCity,Mexico;PeterRossing,Steno
ThoracicInstute,ClevelandClinicAbuDhabi,UnitedArabEmi-
DiabetesCenterCopenhagen;DepartmentofClinicalMedi-
rates;AlessiaArgirò,CardiomyopathyUnit,UniversityofFlo-
cine,UniversityofCopenhagen,Denmark;ShelleyZieroth,
rence,Italy;JohnJ.Atherton,UniversityofQueenslandFaculty
UniversityofManitoba,St.BonifaceHospital,CardiacSciencesofMedicine,CardiologyDepartment,RoyalBrisbaneand
Manitoba,Canada;ShaafAhmad,DivisionofCardiology,The
Women’sHospital,Herston,Brisbane,QLD,Australia;Danielle
UniversityofNorthCarolinaatChapelHill,ChapelHill,NC,
Belardo,PrecisionPrevenveCardiology,LosAngeles,CA,USA;
USA;ShariqUsman,DepartmentofMedicine,Universityof
RaquelCampuzano,DepartmentofCardiology,AlcorconFoun-
MississippiMedicalCenter,Jackson,MS,USA;GeetaAppan-
daonUniversityHospital,Madrid,Spain;NandiniChaerjee,
nah,DivisionofNutrion,DietecsandFoodScience,SchoolDepartmentofMedicine,InstuteofPostGraduateMedicalEd-
ofHealthSciences;CentreforTransformaveNutrionand
ucaonandResearchandSethSukhlalKarnaniMemorialHos-
Health,InstuteforResearch,DevelopmentandInnovaon
pital,Kolkata,WestBengal,India;VijayChopra,HeartFailure
(IRDI),IMUUniversity,BukitJalil,KualaLumpur,Malaysia;Al-
ProgrammeandResearch,MaxSuperSpecialtyHospital,
isonL.Bailey,CentennialHeartatParkridge,ParkridgeMed-
Saket,NewDelhi,India;Marc-AndréCornier,DivisionofEn-
icalCenter,Chaanooga,TN,USA;AhmedBennis,Centerofdocrinology,DiabetesandMetabolicDiseases,Departmentof
Cardiology,IbnRochdUniversityHospital,CasablancaMo-
Medicine,MedicalUniversityofSouthCarolina,Charleston,SC,
rocco;AndreaBrandao,FaculdadedeCiênciasMédicas,Uni-USA;SarahDavies,GPWoodlandsMedicalCentre,Cardi?,
versidadedoEstadodoRiodeJaneiro,RiodeJaneiro,Brazil;WalesPrimaryCareleadforDiabetes,UK;ClemenciadeRueda
JavedButler,DepartmentofMedicine,UniversityofMissis-
Panadero,DepartmentofCardiology,HospitalUniversitario
sippiMedicalCentre,Jackson,MSandBaylorScoandWhiteRamónyCajal,Madrid,Spain;AnastaseDzudie,Department
ResearchInstute,Dallas,TX,USA;MelanieJDavies,Diabetes
ofInternalMedicineandSubspeciales,DoualaGeneralHos-
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LeicesterBiomedicalResearchCentre,Leicester,UK;LubomiravascularAnalycs,Research,andDataScience(CARDS),
Fabryova,MetabolKLINIKsro,DepartmentforDiabetesandProvidenceHeartInstute,ProvidenceHealthSystem,Port-
MetabolicDisorders,LipidClinic,MEDPEDCentre,Biomedicalland,OR,USA;MuhammadShahzebKhan,BaylorScoand
ResearchCentreofSlovakAcademyofSciences,SlovakMed-
WhiteResearchInstute,Dallas,TX;BaylorScoandWhite
icalUniversity,Braslava,Slovakia;Yuan-LinGuo,Cardiometa-TheHeartHospital-Plano,Plano,TX;DepartmentofMedicine,
bolicMedicineCenter,FuwaiHospital,ChineseAcademyofBaylorCollegeofMedicine,Temple,TX,USA;KamleshKhun,
MedicalSciences,Beijing,China;HidetakaItoh,CardiologyDiabetesResearchCentre,UniversityofLeicester,UK;Yuri
Center,ToranomonHospital,Tokyo,Japan;UdayM.Jadhav,Lopan,VolgogradMedicalUniversity,CardiologyCentre,Vol-
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