biostudies-literatureUnknownPop-Busui R<h4>Importance</h4>Heart failure (HF) is a common complication of type 2 diabetes (T2D). Oral semaglutide reduced the risk of major adverse cardiovascular (CV) events (MACE; comprising CV death, nonfatal myocardial infarction, or nonfatal stroke) in people with T2D in the SOUL trial, but the impact on HF outcomes in these participants is unknown.<h4>Objective</h4>To evaluate the effect of oral semaglutide on HF events, MACE, and safety among participants with or without HF at baseline.<h4>Design, setting, and participants</h4>This is a secondary analysis of the double-blind, placebo-controlled, event-driven, phase 3b SOUL randomized clinical trial, which was conducted at 444 centers in 33 countries. Participants were enrolled from June 17, 2019, to March 24, 2021, and had T2D and atherosclJAMA internal medicinehttps://www.ebi.ac.uk/biostudies/studies/S-EPMC12865694biostudies-literatureOral Semaglutide and Heart Failure Outcomes in Persons With Type 2 Diabetes: A Secondary Analysis of the SOUL Randomized Clinical Trial.PMC12865694Deerochanawong CPillay DVucak Loncar JSuciu MPant NKebapci NDonicova VGandy WHFink RIKhaira ASGurkan ETurner WSchelde PBLauro DMihai BWan Mohamed WMIGenovese SOleksyk ODang CHernandez Erazo IDHanackova Prasekova SYuan GJankovec ZCanecki-Varzic SGunstone ABusch RGarza Ruiz JAMitrovic MSchulze JPletea NNPadayachee TPatel MBDe Block CVerges BNardone LYe XHoogenberg KSnyder BMohamad MPoremba JBrinson CMarx NSathyapalan TCigarran SBilen HTatovic DMizote IChun Chung Chow FPeskov ABBustamante Labarta MTabak OJebbink MLaviada Molina HABarrios CSaraiva JFKSethi BKRosenstock JLee CBAbbink-Zandbergen EGonzalez-Galvez GDong XWatada HChaudhury TSOUL Study GroupPaschen BLingvay IKesavadev JBhagwat NMBashkin AKim SGGilbert MPLysenko TATu STConsoli AKoch THusain MRuyatkina LASuwanagool AArechavaleta RChen STWeiss DSoto Gonzalez AFadini GPEsser MBuranapin SMarusic SBusegeanu MMBuse JBLedesma GNNakamura SLalic NLalic KKurtz Lisboa HRShechter MStrajer DEverhart BGLiu JBorot SZemanova JGaborit BComlekci ASugawara MShimon IFließer-Gorzer ELam CSPSchlosser RPiskorz DGomez Mesa JEPantalone KHewitt MJinnouchi HCulak JIgnatyeva AIwata HPrier KFasching PChoi SHBain SCPunthakee ZPedersen SGonzalez-Orozco LBhorat QEHarris KPashkovska NMazon Ramos PReddy VSGmitrov JZalevskaya AKyselova PMurray AVOnaka HRay SNakhle SNSanchez Garcia RFrancisco JGirithara GMann JFELeite SOThrasher JRJohnson DMKargina LChochinov RHInzucchi SELuquez CKuskalo PBayram FSmahelova AMishchenko Golinskaya ODesai AJohnston PBuscemi SKiyosue AKooy ARandeva HSingh KPBondarets IOlsen AMZThomas NHuffman DSueyoshi AGarcia Ordonez MAKunitsyna MLopez Suarez AKrishnasamy SSAyele EYahaya NHernandez Ruiz EASimegi-Djekic VEbisui OOsonoi TSeeber MEKaydashev ILane WSAdam NLBlack DMyshanych GTran HGorgojo-Martinez JJBeljic Zivkovic TBays HEMittal NSariakcali BDjordjevic MBayer Tanggaard KDhatariya KBaker CLorenzatti AJCitarrella RStokic EIgarashi MSingh JJodar EChaidarun SSMohan VDang AHTan FHSKikovic SZemel LRField BReed JCHGaysina LDimic DBoonyavarakul ASchaum TDaxini BMot ACAllison DCOdugbesan AOBeca STantiwong POiwa APieber TMin KWeisnagel JYanovskaya MEHanaoka KFonseca AGTAharon-Hananel GYuki HPrakash APoulter NROlsovsky JJacob JJMaranghi MAnderson MWMikkelsen DUrbanovych ATellier GDi Carlo AKobalava ZLeelawattana RMurdolo GPop-Busui RJi LWenzl-Bauer VLacka JEzaki HIdogaki AMaliar KTusek SCondit JGarcia Cantu EATinahones FCornett GMPatel DRasmussen SYoon KHMakan Vde Valk HWLieverse LPesic MKernohan AMcknight JASaprina TVEagerton DCAmod ADolezalova BDaboul NYMirza LPurighalla RSFrolova EVFitz-Patrick DMarwah TMonier AMorales Portillo CJain SMDoi MLandewe-Cleuren SANTLevenson DHundza VMathieu CDelgado Lista JLillestol MJJackson RAHochberg IOng TKRisser JAKruljac IFogarty CMHeyns EHasan SLupoli RNatsuaki MCerna KVidotti MHMontalban Carrasco CPetrosyan OEbenbichler CMacKinnon IJPhilip SHaluzik MWarren MLPratley RENtusi NOldenburg-Ligtenberg CGhosh SSaboo BPolovina SPotier LKoleny DNicol PRRansom TPPGopalakrishnan UAMayet LSonmez YALarroumet ALudemann Jvan Bemmel TKahrmann GZilov ACernea SBacus HBWyatt NFujino SShabelnikova OYWierum CAlasaad HGupta DConnelly KABajaj CTicinovic Kurir TDjukic ABajaj HChahin MIFam TLRea RRThulaseedharan NKEnglish PNoronha LChu JWTytus RReddy SPGrimmer PArambasick JYusoff Azmi Merican NSAbdul Ghani RBanda Elizondo RGCrisan CMbogua CNGarcia Ulloa ACStaudenmeyer AEspinoza Peralta DDesouza CVEmerson SSJhund PSChilka STraylor HAggarwal NKadam YFilip IJantzi CAnghel VThuan JFZyangirova STMontero MMurakami TAngelo Cadena Bonfanti AChadha MMorales Villegas ECTirosh AO'Donnell PKempe HPTanabe MLee WJLindsay ROznerova MBirkenfeld ALAhbab SPorter JJerkins TJardula MFChaicha-Brom TNishida YMurthy SSriwijitkamol ATsoukas MBenjachareonwong SNielsen OWMa RCWPradignac AVisco VETandron IJDoshi AGagianas PJSiddiqui IAPrager RSharma SKCannon KGuclu MOtroshchenko OGarcia Quintana ABaruah MPPozzi JMMankovsky BSahay RSuplotova LAZagrebelnaya OLovre DVishlitzky VOhashi HNagelberg SSuryanarayana KMLapauw BLee JSetola ERao PVEgstrup KRatnasingam JBhargava ATandon NRahelic DTanaka MAxthelm CBrautigam DPowell TPlasil RVathesatogkit PCasaubon LBian FHovingh GKVrkoc JGiorgino FAndreozzi FNicoara ATsur AAgaiby JMKang ESSalles JEHuang CNRoman GHata YAstamirova KPedersen-Bjergaard UPella DTuratti LAAPerez Manghi FAcibucu FKanungo AKKellerer MMedina Pech CESosovec DBuranasupkajorn PPark AAwasty VCavender MASivalingam KKocak MSofer YBudoff MJLakha DROguz ADuyck FDomae HMcGuire DKMulvagh SLFranco DRvan Raalte DEngelmann MDMChawla RJoshi MRasouli NJoshi PRose LGregersen SDeanfield JESergeeva-Kondrachenko MYFabris Vitkovic DBao SMancini JGBOh FPhilis-Tsimikas AfalseOral Semaglutide and Heart Failure Outcomes in Persons With Type 2 Diabetes: A Secondary Analysis of the SOUL Randomized Clinical Trial.<h4>Importance</h4>Heart failure (HF) is a common complication of type 2 diabetes (T2D). Oral semaglutide reduced the risk of major adverse cardiovascular (CV) events (MACE; comprising CV death, nonfatal myocardial infarction, or nonfatal stroke) in people with T2D in the SOUL trial, but the impact on HF outcomes in these participants is unknown.<h4>Objective</h4>To evaluate the effect of oral semaglutide on HF events, MACE, and safety among participants with or without HF at baseline.<h4>Design, setting, and participants</h4>This is a secondary analysis of the double-blind, placebo-controlled, event-driven, phase 3b SOUL randomized clinical trial, which was conducted at 444 centers in 33 countries. Participants were enrolled from June 17, 2019, to March 24, 2021, and had T2D and atheroscl2026-01-01T00:00:00Z2026 Feb2026-07-15T13:56:57.294Z2026-07-05T03:12:19.891ZS-EPMC128656944162780210.1001/jamainternmed.2025.7774