PMID- 37635157
OWN - NLM
STAT- MEDLINE
DCOM- 20230918
LR  - 20240425
IS  - 1546-170X (Electronic)
IS  - 1078-8956 (Print)
IS  - 1078-8956 (Linking)
VI  - 29
IP  - 9
DP  - 2023 Sep
TI  - Semaglutide in HFpEF across obesity class and by body weight reduction: a 
      prespecified analysis of the STEP-HFpEF trial.
PG  - 2358-2365
LID - 10.1038/s41591-023-02526-x [doi]
AB  - In the STEP-HFpEF trial, semaglutide improved symptoms, physical limitations and 
      exercise function and reduced body weight in patients with obesity phenotype of 
      heart failure and preserved ejection fraction (HFpEF). This prespecified analysis 
      examined the effects of semaglutide on dual primary endpoints (change in Kansas 
      City Cardiomyopathy Questionnaire-Clinical Summary Score (KCCQ-CSS) and body 
      weight) and confirmatory secondary endpoints (change in 6-minute walk distance 
      (6MWD), hierarchical composite (death, HF events, change in KCCQ-CSS and 6MWD) 
      and change in C-reactive protein (CRP)) across obesity classes I-III (body mass 
      index (BMI) 30.0-34.9 kg m(-)(2), 35.0-39.9 kg m(-)(2) and >/=40 kg m(-)(2)) and 
      according to body weight reduction with semaglutide after 52 weeks. Semaglutide 
      consistently improved all outcomes across obesity categories (P value for 
      treatment effects x BMI interactions = not significant for all). In 
      semaglutide-treated patients, improvements in KCCQ-CSS, 6MWD and CRP were greater 
      with larger body weight reduction (for example, 6.4-point (95% confidence 
      interval (CI): 4.1, 8.8) and 14.4-m (95% CI: 5.5, 23.3) improvements in KCCQ-CSS 
      and 6MWD for each 10% body weight reduction). In participants with obesity 
      phenotype of HFpEF, semaglutide improved symptoms, physical limitations and 
      exercise function and reduced inflammation and body weight across obesity 
      categories. In semaglutide-treated patients, the magnitude of benefit was 
      directly related to the extent of weight loss. Collectively, these data support 
      semaglutide-mediated weight loss as a key treatment strategy in patients with 
      obesity phenotype of HFpEF. ClinicalTrials.gov identifier: NCT04788511 .
CI  - (c) 2023. The Author(s).
FAU - Borlaug, Barry A
AU  - Borlaug BA
AUID- ORCID: 0000-0001-9375-0596
AD  - Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, USA.
FAU - Kitzman, Dalane W
AU  - Kitzman DW
AD  - Department of Cardiovascular Medicine and Section on Geriatrics and Gerontology, 
      Wake Forest University School of Medicine, Winston-Salem, NC, USA.
FAU - Davies, Melanie J
AU  - Davies MJ
AD  - Diabetes Research Centre, University of Leicester, Leicester, UK.
AD  - NIHR Leicester Biomedical Research Centre, Leicester, UK.
FAU - Rasmussen, Soren
AU  - Rasmussen S
AD  - Novo Nordisk A/S, Soborg, Denmark.
FAU - Barros, Eric
AU  - Barros E
AUID- ORCID: 0000-0001-6613-4181
AD  - Novo Nordisk A/S, Soborg, Denmark.
FAU - Butler, Javed
AU  - Butler J
AD  - Baylor Scott and White Research Institute, Dallas, TX and Department of Medicine, 
      University of Mississippi, Jackson, MS, USA.
FAU - Einfeldt, Mette Nygaard
AU  - Einfeldt MN
AD  - Novo Nordisk A/S, Soborg, Denmark.
FAU - Hovingh, G Kees
AU  - Hovingh GK
AD  - Novo Nordisk A/S, Soborg, Denmark.
FAU - Moller, Daniel Vega
AU  - Moller DV
AD  - Novo Nordisk A/S, Soborg, Denmark.
FAU - Petrie, Mark C
AU  - Petrie MC
AD  - School of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, 
      UK.
FAU - Shah, Sanjiv J
AU  - Shah SJ
AUID- ORCID: 0000-0002-5655-8201
AD  - Division of Cardiology, Department of Medicine, Northwestern University Feinberg 
      School of Medicine, Chicago, IL, USA.
FAU - Verma, Subodh
AU  - Verma S
AUID- ORCID: 0000-0002-4018-8533
AD  - Division of Cardiac Surgery, Li Ka Shing Knowledge Institute of St. Michael's 
      Hospital, Unity Health Toronto, University of Toronto, Toronto, ON, Canada.
FAU - Abhayaratna, Walter
AU  - Abhayaratna W
AUID- ORCID: 0000-0002-4908-0641
AD  - College of Health and Medicine, The Australian National University, Canberra, 
      ACT, Australia.
FAU - Ahmed, Fozia Z
AU  - Ahmed FZ
AD  - Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, 
      University of Manchester, Manchester, UK.
FAU - Chopra, Vijay
AU  - Chopra V
AD  - Clinical Cardiology, Heart Failure and Research, Max Super Specialty Hospital, 
      Saket, New Delhi, India.
FAU - Ezekowitz, Justin
AU  - Ezekowitz J
AUID- ORCID: 0000-0002-2724-4086
AD  - University of Alberta, Edmonton, AB, Canada.
FAU - Fu, Michael
AU  - Fu M
AD  - Section of Cardiology, Department of Medicine, Sahlgrenska University 
      Hospital-Ostra, Gothenburg, Sweden.
FAU - Ito, Hiroshi
AU  - Ito H
AD  - Department of General Internal Medicine 3, Kawasaki Medical School, Okayama, 
      Japan.
FAU - Lelonek, Malgorzata
AU  - Lelonek M
AD  - Department of Noninvasive Cardiology, Medical University of Lodz, Lodz, Poland.
FAU - Melenovsky, Vojtech
AU  - Melenovsky V
AD  - Institute for Clinical and Experimental Medicine - IKEM, Prague, Czech Republic.
FAU - Nunez, Julio
AU  - Nunez J
AUID- ORCID: 0000-0003-1672-7119
AD  - Hospital Clinico Universitario de Valencia, INCLIVA, Universidad de Valencia, and 
      CIBER Cardiovascular, Valencia, Spain.
FAU - Perna, Eduardo
AU  - Perna E
AUID- ORCID: 0000-0002-9977-7623
AD  - Instituto de Cardiologia J. F. Cabral, Corrientes, Argentina.
FAU - Schou, Morten
AU  - Schou M
AD  - Department of Cardiology, Herlev-Gentofte Hospital, University of Copenhagen, 
      Herlev, Denmark.
FAU - Senni, Michele
AU  - Senni M
AUID- ORCID: 0000-0001-5502-7882
AD  - Cardiovascular Department, ASST Papa Giovanni XXIII Hospital, Bergamo, Italy.
FAU - van der Meer, Peter
AU  - van der Meer P
AUID- ORCID: 0000-0002-9705-4413
AD  - Department of Cardiology, University Medical Center Groningen, University of 
      Groningen, Groningen, The Netherlands.
FAU - Von Lewinski, Dirk
AU  - Von Lewinski D
AUID- ORCID: 0000-0001-9996-6128
AD  - Division of Cardiology, Medical University of Graz, Graz, Austria.
FAU - Wolf, Dennis
AU  - Wolf D
AUID- ORCID: 0000-0003-1525-4348
AD  - Cardiology and Angiology, Medical Center - University of Freiburg, Faculty of 
      Medicine, University of Freiburg, Freiburg, Germany.
FAU - Kosiborod, Mikhail N
AU  - Kosiborod MN
AUID- ORCID: 0000-0002-3750-9789
AD  - Department of Cardiovascular Disease, Saint Luke's Mid America Heart Institute, 
      University of Missouri-Kansas City School of Medicine, Kansas City, MO, USA. 
      mkosiborod@saint-lukes.org.
LA  - eng
SI  - ClinicalTrials.gov/NCT04788511
GR  - R01 HL162828/HL/NHLBI NIH HHS/United States
GR  - R01 AG078153/AG/NIA NIH HHS/United States
GR  - R01 HL140731/HL/NHLBI NIH HHS/United States
GR  - R01 HL128526/HL/NHLBI NIH HHS/United States
GR  - R01 HL127028/HL/NHLBI NIH HHS/United States
GR  - R01 AG018915/AG/NIA NIH HHS/United States
GR  - U24 AG059624/AG/NIA NIH HHS/United States
GR  - R01 HL107577/HL/NHLBI NIH HHS/United States
GR  - R01 HL149423/HL/NHLBI NIH HHS/United States
GR  - P30 AG021332/AG/NIA NIH HHS/United States
GR  - UL1 TR002384/TR/NCATS NIH HHS/United States
GR  - R01 AG045551/AG/NIA NIH HHS/United States
GR  - U54 HL160273/HL/NHLBI NIH HHS/United States
GR  - U01 HL160272/HL/NHLBI NIH HHS/United States
GR  - U01 HL160226/HL/NHLBI NIH HHS/United States
GR  - U01 AG076928/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20230827
PL  - United States
TA  - Nat Med
JT  - Nature medicine
JID - 9502015
RN  - 53AXN4NNHX (semaglutide)
RN  - 9007-41-4 (C-Reactive Protein)
SB  - IM
MH  - Humans
MH  - *Heart Failure
MH  - Stroke Volume
MH  - Body Weight
MH  - Weight Loss
MH  - Obesity/complications/drug therapy
MH  - C-Reactive Protein
PMC - PMC10504076
COIS- B.A.B. receives research support from the National Institutes of Health (NIH) and 
      the US Department of Defense as well as research grant funding from AstraZeneca, 
      Axon, GlaxoSmithKline, Medtronic, Mesoblast, Novo Nordisk, Rivus and Tenax 
      Therapeutics. B.A.B. has also served as a consultant for Actelion, Amgen, Aria, 
      Axon Therapies, BD Biosciences, Boehringer Ingelheim, Cytokinetics, Edwards 
      Lifesciences, Eli Lilly, Imbria, Janssen, Merck, Novo Nordisk, NGM 
      Biopharmaceuticals, NXT and VADovations and is named as an inventor (US patent 
      no. 10,307,179) for the tools and approach for a minimally invasive pericardial 
      modification procedure to treat heart failure. D.W.K. was supported, in part, by 
      the Kermit Glenn Phillips II Chair in Cardiovascular Medicine and NIH grants 
      U01AG076928, R01AG078153, R01AG045551, R01AG18915 and U01HL160272 and reports 
      receiving honoraria as a consultant for Bayer, Corvia Medical, Boehringer 
      Ingelheim, Ketyo, Rivus, Novo Nordisk, AstraZeneca, Pfizer and Novartis; grant 
      funding from Novartis, Bayer, Novo Nordisk, Rivus, Pfizer and AstraZeneca; and 
      stock ownership in Gilead Sciences. M.J.D. has acted as a consultant, advisory 
      board member and speaker for Boehringer Ingelheim, Eli Lilly, Novo Nordisk and 
      Sanofi; an advisory board member and speaker for AstraZeneca; an advisory board 
      member for Pfizer, Medtronic and ShouTi Pharma Inc.; and a speaker for Novartis, 
      Sanofi and Amgen. M.D. has received grants in support of investigator and 
      investigator-initiated trials from AstraZeneca, Sanofi-Aventis, Eli Lilly, 
      Boehringer Ingelheim, Janssen and Novo Nordisk. J.B. is a consultant to Abbott, 
      American Regent, Amgen, Applied Therapeutic, AstraZeneca, Bayer, Boehringer 
      Ingelheim, Bristol Myers Squibb, Cardiac Dimension, Cardior, CVRx, Cytokinetics, 
      Edwards, Element Science, Innolife, Impulse Dynamics, Imbria, Inventiva, Lexicon, 
      Eli Lilly, LivaNova, Janssen, Medtronics, Merck, Occlutech, Novartis, Novo 
      Nordisk, Pfizer, Pharmacosmos, Pharmain, Roche, Sequana, SQ Innovation, 3live and 
      Vifor. M.C.P. has received research grants or consultancy fees from AstraZeneca, 
      Boehringer Ingelheim, Eli Lilly, Napp Pharmaceuticals, Novartis, Novo Nordisk, 
      Pharmacosmos, Roche and SQ Innovations; has served on committees for AbbVie, 
      Akero, Alnylam, AstraZeneca, Bayer, Boehringer Ingelheim, GlaxoSmithKline, New 
      Amsterdam, Novo Nordisk, Resverlogix and Teikoku; and is Director of Global 
      Clinical Trial Partners. S.J.S. reports receiving consulting fees from Abbott, 
      AstraZeneca, Amgen, Aria CV, Axon Therapies, Bayer, Boehringer Ingelheim, Boston 
      Scientific, Bristol Myers Squibb, Cyclerion, Cytokinetics, Edwards Lifesciences, 
      Eidos, Imara, Impulse Dynamics, Intellia, Ionis, Eli Lilly, Merck, Metabolic 
      Flux, MyoKardia, NGM Biopharmaceuticals, Novartis, Novo Nordisk, Pfizer, 
      Prothena, Regeneron, Rivus, Sardocor, Shifamed, Tenax, Tenaya and United 
      Therapeutics. S.V. reports speaking honoraria and/or consulting fees from Abbott, 
      AstraZeneca, Bayer, Boehringer Ingelheim, Novo Nordisk, Novartis, Merck, 
      PhaseBio, HLS Therapeutics, Amarin, Eli Lilly, Janssen, Pfizer, TIMI, Canadian 
      Medical and Surgical Knowledge Translation Research Group. W.A. reports honoraria 
      and/or consulting fees from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, 
      Novartis and Novo Nordisk. F.Z.A. reports honoraria and/or consulting fees from 
      Abbott, AstraZeneca, Medtronic, Novo Nordisk, Occlutech, Pharmacosmos and Vifor. 
      V.C. reports speaker fees from AstraZeneca, Boehringer Ingelheim, Cipla, Dr. 
      Reddy's, Lupin, Novartis, Novo Nordisk, Mankind, Pfizer, Sanofi, Sun Pharma and 
      Torrent. J.E. reports research support for trial leadership from American Regent, 
      Applied Therapeutics, Bayer, Cytokinetics, Merck and Novo Nordisk; honoraria for 
      consultancy from AstraZeneca, Bayer, Boehringer Ingelheim, Novartis, Novo Nordisk 
      and Otsuka; and service as an advisor to US2.ai. M.F. reports no conflicts of 
      interest. H.I. reports honoraria and/or consulting fees from AstraZeneca, Bayer, 
      Boehringer Ingelheim, Daiichi-Sankyo, Mochida, Novartis and Novo Nordisk. M.L. 
      reports honoraria and/or consulting fees from AstraZeneca, Bayer, Boehringer 
      Ingelheim, Ewopharma, Gedeon Richter, Novartis, Novo Nordisk, Roche and Servier. 
      V.M. reports consulting fees from Bayer, Merck Sharp & Dohme and Novo Nordisk; 
      research grants from Regeneron; and research support from the National Institute 
      for Research of Metabolic and Cardiovascular Diseases (Program EXCELES, project 
      no. LX22NPO5104), funded by the European Union-Next Generation EU. J.N. reports 
      honoraria and/or consulting fees from Alleviant, AstraZeneca, Bayer, Boehringer 
      Ingelheim, Cytokinetics, Pfizer, Novartis, Novo Nordisk, Rovi and Vifor. E.P. 
      reports honoraria from Novo Nordisk. M. Schou reports speaker fees from 
      AstraZeneca, Boehringer Ingelheim, Novartis and Novo Nordisk. M. Senni reports 
      honoraria and/or consulting fees from Abbott, AstraZeneca, Bayer, Boehringer 
      Ingelheim, Merck, Merck Sharp & Dohme, Novartis, Novo Nordisk and Vifor. P.v.d.M. 
      reports institutional payments for consultancy fees and/or grants from 
      AstraZeneca, Boehringer Ingelheim, BridgeBio, Ionis, Novartis, Novo Nordisk, 
      Pfizer, Pharmacosmoc, Pharma Nord and Vifor. D.V.L. reports honoraria and/or 
      consulting fees from AstraZeneca, Bayer, Boehringer Ingelheim, Merck Sharp & 
      Dohme, Novartis, Novo Nordisk, Recardio, Sanofi, Sanova and Vaxxinity. D.W. 
      reports consultancy fees from Novo Nordisk. S.R., E.B., M.N.E., G.K.H. and D.V.M. 
      are employees of and hold shares in Novo Nordisk A/S. M.N.K. served as a 
      consultant or on an advisory board for 35Pharma, Alnylam, Amgen, Applied 
      Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Cytokinetics, Dexcom, Eli 
      Lilly, Esperion Therapeutics, Janssen, Lexicon Pharmaceuticals, Merck (Diabetes 
      and Cardiovascular), Novo Nordisk, Pharmacosmos, Pfizer, scPharmaceuticals, 
      Sanofi, Structure Therapeutics, Vifor and Youngene Therapeutics. M.N.K. has also 
      received research grants from AstraZeneca, Boehringer Ingelheim and Pfizer; holds 
      stock in Artera Health and Saghmos Therapeutics; has received honoraria from 
      AstraZeneca, Boehringer Ingelheim and Novo Nordisk; and has received other 
      research support from AstraZeneca.
EDAT- 2023/08/28 00:41
MHDA- 2023/09/18 12:42
PMCR- 2023/08/27
CRDT- 2023/08/27 23:02
PHST- 2023/07/10 00:00 [received]
PHST- 2023/08/01 00:00 [accepted]
PHST- 2023/09/18 12:42 [medline]
PHST- 2023/08/28 00:41 [pubmed]
PHST- 2023/08/27 23:02 [entrez]
PHST- 2023/08/27 00:00 [pmc-release]
AID - 10.1038/s41591-023-02526-x [pii]
AID - 2526 [pii]
AID - 10.1038/s41591-023-02526-x [doi]
PST - ppublish
SO  - Nat Med. 2023 Sep;29(9):2358-2365. doi: 10.1038/s41591-023-02526-x. Epub 2023 Aug 
      27.