Research Study to Look at How Well Semaglutide Works in People Living With Heart Failure, Obesity and Type 2 Diabetes

Recruitment Status
COMPLETED
(See Contacts and Locations)Verified October 2025 by Novo Nordisk A/S
Sponsor
Novo Nordisk A/S
Information Provided by (Responsible Party)
Novo Nordisk A/S
Clinicaltrials.gov Identifier
NCT04916470
Other Study ID Numbers:
EX9536-4773
First Submitted
May 31, 2021
First Posted
June 6, 2021
Last Update Posted
November 25, 2025
Last Verified
October 2025

ClinicalTrials.gov processed this data on November 2025Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

Condition or DiseaseIntervention/Treatment
Heart Failure With Preserved Ejection Fraction (HFpEF) and Diabetes Mellitus, Type 2
Drug: SemaglutideDrug: Placebo (Semaglutide)

Study Design

Study TypeInterventional
Actual Enrollment617 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingQuadruple
Primary PurposeTreatment
Official TitleEffect of Semaglutide 2.4 mg Once-weekly on Function and Symptoms in Subjects With Obesity-related Heart Failure With Preserved Ejection Fraction, and Type 2 Diabetes
Study Start DateJune 14, 2021
Actual Primary Completion DateOctober 10, 2023
Actual Study Completion DateOctober 10, 2023

Groups and Cohorts

Group/CohortIntervention/Treatment
Semaglutide 2.4 mg once weekly (OW)
Participants will receive semaglutide injections for 52 weeks.
Drug: Semaglutide
Participants will receive semaglutide subcutaneous (s.c.; under the skin) injection(s) once-weekly for 52 weeks. Dose will be gradually increased to 2.4 mg: 0.25 mg from week 1 to 4, 0.5 mg from week 5 to 8, 1.0 mg from week 9 to 12, 1.7 mg from week 13 to 16 and 2.4 mg from week 17 to week 52.
Semaglutide placebo OW
Participants will receive semaglutide placebo injections for 52 weeks.
Drug: Placebo (Semaglutide)
Participants will receive semaglutide matching placebo s.c. injection(s) once-weekly for 52 weeks.

Outcome Measures

Primary Outcome Measures
  1. Change in KCCQ (Kansas City Cardiomyopathy Questionnaire) clinical summary score
    Score on a scale of 0 to 100 where the score 100 means the least burden for the participant.
  2. Change in body weight
    Percentage (%)
Secondary Outcome Measures
  1. Change in 6-minute walking distance
    Measured in metres
  2. Hierarchical composite of time to all-cause death
    Measured as total wins for each treatment group.
  3. Hierarchical composite of number of heart failure events requiring hospitalisation or urgent heart failure visit
    Measured as total wins for each treatment group
  4. Hierarchical composite of time to first heart failure event requiring hospitalisation or urgent heart failure visit
    Measured as total wins for each treatment group.
  5. Hierarchical composite of difference at least 15 inKansas City Cardiomyopathy Questionnaire (KCCQ) clinical summary score change from baseline to 52 weeks
    Measured as total wins for each treatment group.
  6. Hierarchical composite of difference at least 10 in KCCQ clinical summary score change from baseline to 52 weeks
    Measured as total wins for each treatment group.
  7. Hierarchical composite of difference at least 5 in KCCQ clinical summary score change from baseline to 52 weeks
    Measured as total wins for each treatment group.
  8. Hierarchical composite of difference at least 30 metres in six-minute walking distance change from baseline to 52 weeks (assessed by the win ratio)
    Measured as total wins for each treatment group.
  9. Change in C-Reactive Protein
    Presented as ratio to baseline
  10. Participant achieving 10% weight loss or more (Yes/No)
    Count of participants
  11. Participant achieving 15% weight loss or more (Yes/No)
    Count of participants
  12. Participant achieving 20% weight loss or more (Yes/No)
    Count of participants
  13. Participant improving 5 points or more in KCCQ clinical summary score
    Count of participants
  14. Participant improving 10 points or more in KCCQ clinical summary score (Yes/No)
    Count of participants
  15. Change in KCCQ overall summary score
    Score on a scale of 0 to 100 where the score 100 means the least burden for the participant.
  16. Participant achieving threshold for clinically meaningful within-subject change in KCCQ-CSS
    Count of participants
  17. Participant achieving threshold for clinically meaningful within-subject change in 6MWD
    Count of participants
  18. Change in waist circumference
    Measured in centimetre (cm)
  19. Change in systolic blood pressure
    Measured in millimetre of mercury (mmHg)
  20. Change in glycated haemoglobin (HbA1c)
    Measured in percentage (%)-point
  21. Number of treatment emergent severe or clinically significant hypoglycaemia episodes
    Count of events

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
Inclusion Criteria
Male or female, age above or equal to 18 years at the time of signing informed consent.
Body mass index (BMI) greater than or equal to 30.0 kg/m\^2
New York Heart Association (NYHA) Class II-IV
Left ventricular ejection fraction (LVEF) greater than or equal to 45% at screening
Diagnosed with T2D greater than or equal to 90 days prior to the day of screening
HbA1c of below or equal to 10.0% as measured at the screening visit
Exclusion Criteria
A self-reported change in body weight greater than 5 kg (11 lbs) within 90 days before screening irrespective of medical records
Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within 90 days prior to screening or in the period between screening and randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination.

Contacts and Locations

Sponsors and CollaboratorsNovo Nordisk A/S
Locations
Eastern Shore Rsrch Inst, LLC | Fairhope Alabama, United States, 36532Mobile Heart Specialists | Mobile Alabama, United States, 36608National Heart Institute Cal | Beverly Hills California, United States, 90211John Muir Physicians Network | Concord California, United States, 94520Valley Clinical Trials | Covina California, United States, 91723Keck Medical Center of USC - Outpatient Clinic | Los Angeles California, United States, 90033Valley Clinical Trials, Inc. | Northridge California, United States, 91325Lundquist Inst-Biomed Innovtn | Torrance California, United States, 90502New West Physicians,Inc. | Golden Colorado, United States, 80401Excel Med Ctr Clinical Trials | Boca Raton Florida, United States, 33434Bay Area Cardiology Associates, P.A. | Brandon Florida, United States, 33511Baptist Heart Specialists_Jacksonville | Jacksonville Florida, United States, 32258CV Res Ctr of S Florida | Miami Florida, United States, 33173Endeavor Health Clinical Operations-NCH | Arlington Heights Illinois, United States, 60005Endeavor Health Glenbook Hosp | Evanston Illinois, United States, 60201Northwestern University_Chicago_0 | Evanston Illinois, United States, 60208Chicago Medical Research LLC | Hazel Crest Illinois, United States, 60429Deaconess Specialty Physicians | Evansville Indiana, United States, 47747Ascension St. Vincent Medical Group | Indianapolis Indiana, United States, 46260Cardiovascular Rsrch of NW_IN | Munster Indiana, United States, 46321Cotton-O'Neil Heart Center | Topeka Kansas, United States, 66606Baptist Health Woodland | Elizabethtown Kentucky, United States, 42701The Research Group of Lexington LLC | Lexington Kentucky, United States, 40503Baptist Health Louisville | Louisville Kentucky, United States, 40207Grace Research, LLC | Bossier City Louisiana, United States, 71111Heart Clinic of Hammond | Hammond Louisiana, United States, 70403Clinical Trials of Ame, LLC | Monroe Louisiana, United States, 71201Grace Research, LLC_Shreveport | Shreveport Louisiana, United States, 71105Louisiana Heart Center_Slidell | Slidell Louisiana, United States, 70458Ascension Saint Agnes Heart Ca | Baltimore Maryland, United States, 21229MedStar Good Samaritan Hosp | Baltimore Maryland, United States, 21239John Hopkins Hospital | Baltimore Maryland, United States, 21287Elite Research Center | Flint Michigan, United States, 48532Mayo Clinic | Rochester Minnesota, United States, 55905Univ of Mississippi Med Ctr | Jackson Mississippi, United States, 39216Saint Luke's Hospital of Kansas City | Kansas City Missouri, United States, 64111St Louis Heart & Vascular, P.C. | St Louis Missouri, United States, 63136Bryan Heart | Lincoln Nebraska, United States, 68506CHI Health Clinic Cardiology (CUMC - Bergan Mercy) | Omaha Nebraska, United States, 68124St Francis Hospital Lindner Research Center | Greenvale New York, United States, 11548NY Presbyt Hosp-W Cornell Med | New York New York, United States, 10021Carteret Medical Group | Morehead City North Carolina, United States, 28557Wake Forest Baptist Health | Winston-Salem North Carolina, United States, 27157Lindner Center,Christ Hospital | Cincinnati Ohio, United States, 45219Abington Memorial Hospital | Abington Pennsylvania, United States, 19001Hospital of University of Pennsylvania | Philadelphia Pennsylvania, United States, 19104Sanford Health_Sioux Falls | Sioux Falls South Dakota, United States, 57117Tennessee Center for Clinical Trials | Tullahoma Tennessee, United States, 37388University of Texas Southwestern Medical Center | Dallas Texas, United States, 75390Angio Cardiac Care of Texas | Houston Texas, United States, 77025Cardiology Consultants of Danville Inc. | Danville Virginia, United States, 24541Virginia Heart | Falls Church Virginia, United States, 22042Virginia Commonwealth University | Richmond Virginia, United States, 23298-5058Virginia Commonwealth University | Richmond Virginia, United States, 23298CEMEDIC | CABA Buenos Aires, Argentina, C1440CFDCentro de Investigación y Prevención Cardiovascular | CABA , Argentina, C1061AAS.Centro de Investigación y Prevención Cardiovascular | CABA , Argentina, C1119ACNCEMEDIC | CABA , Argentina, C1440CFDCardiología Palermo Duplicate | Ciudad Autónoma de Buenos Aire , Argentina, 1425Cardiología Palermo | Ciudad Autónoma de Buenos Aire , Argentina, 1425Instituto de Cardiología de Corrientes | Corrientes , Argentina, W3400AMZConsultorio Integral de Atención al Diabético | Morón , Argentina, B1708IFFSanatorio Britanico S.A. | Rosario, Santa Fe , Argentina, S2000CVBKrankenhaus St. Josef Braunau | Braunau am Inn , Austria, 5280Medizinische Universität Graz | Graz , Austria, 8036Medizinische Universität Graz | Graz , Austria, A 8036Fließer-Görzer [Ordination] | Saint Stefan , Austria, 8511Medizinische Universität Wien | Vienna , Austria, 1090Klinik Favoriten | Vienna , Austria, 1100Imed 19- privat | Vienna , Austria, 1190AKH Universitätsklinik für Innere Medizin II | Vienna , Austria, A 1090Universitätsklinik für Innere Medizin II | Vienna , Austria, A 1090University of Calgary_Calgary | Calgary Alberta, Canada, T2N 4Z6Univ of Alberta Hosp Edmonton | Edmonton Alberta, Canada, T6G 2B7North Shore Heart Centre | North Vancouver British Columbia, Canada, V7M 2H4SMH Cardiology Clinical Trials Inc. | Surrey British Columbia, Canada, V3V 0C6St. Boniface Hospital | Winnipeg Manitoba, Canada, R2H 2HA6Cambridge Cardiac Care Centre | Cambridge Ontario, Canada, N1R 6V6Partnrs Adv Cardio Eval (PACE) | Newmarket Ontario, Canada, L3Y 2P6Oakville Cardiovascular Research LP | Oakville Ontario, Canada, L6K 3W7Heart Health Institute Research, Inc. | Scarborough Village Ontario, Canada, M1B 4Z8Dr. Louis Yao | Weston Ontario, Canada, M9N 1W4ViaCar Recherche Clinique Inc | Brossard Quebec, Canada, J4Z 2K9Applied Med Inf Res | Montreal Quebec, Canada, H4A 3T2Ctr de Med Metab de Lanaudiere | Terrebonne Quebec, Canada, J6X 4P7Institut universitaire de cardiologie | Québec , Canada, G1V 4G5Edumed Broumov | Broumov , Czechia, 550 01Fakultní poliklinika VFN ambulance Srdecniho selhani | Prague , Czechia, 120 00IKEM | Prague , Czechia, 140 21MEDICON a.s. | Prague , Czechia, 170 00Poliklinika Holešovice VISIONARY - Medicon Pharm s.r.o. | Prague , Czechia, 170 00Charité - Campus Virchow-Klinikum - Kardiologie, Angiologie und Intensivmedizin (CRU) | Berlin , Germany, 13353Cardiologicum Dresden und Pirna - MVZ "Am Felsenkeller" (Dresden) | Dresden , Germany, 01277Zentrum fuer klinische Studien Suedbrandenburg GmbH | Elsterwerda , Germany, 04910MVZ CCB Frankfurt und Main-Taunus GbR | Frankfurt , Germany, 60389Medical Center - University Of Freiburg | Freiburg im Breisgau , Germany, 79106Universitätsklinikum Freiburg - Medical Center | Freiburg im Breisgau , Germany, 79106B. Braun Ambulantes Herzzentrum Kassel MVZ GmbH | Kassel , Germany, 34121Universitätsklinikum Leipzig - Klinik und Poliklinik für Kardiologie | Leipzig , Germany, 04103Universitätsmedizin Mainz, Kardiologie I, Studienzentrum | Mainz , Germany, 55131Universitatsklinikum Würzburg - Zentrum für Herzinsuffizienz | Würzburg , Germany, 97078Lausmed Kft. | Baja Bács-Kiskun county, Hungary, 6500Selye János Kórház | Komárom Komárom-Esztergom, Hungary, 2921Szent Margit Rendelőintézet Nonprofit Kft. | Budapest , Hungary, 1032Semmelweis Egyetem Szent Rókus Klinikai Tömb | Budapest , Hungary, 1085Gottsegen György Országos Kardiológiai Intézet | Budapest , Hungary, 1096Semmelweis Egyetem Városmajori Szív- és Érgyógyászat | Budapest , Hungary, 1122Jahn Ferenc Dél-pesti Kórház és Rendelőintézet | Budapest , Hungary, 1204DE KK Kardiológiai és Szívsebészeti klinika | Debrecen , Hungary, 4032Borsod-Abaúj-Zemplén Megyei Központi Kórház | Miskolc , Hungary, 3526Zala Megyei Szent Rafael Kórház | Zalaegerszeg , Hungary, 8900Krishna Institute of medical sciences Ltd | Secunderabad A.P., India, 500 003CIMS- Care Institute of Medical Sciences | Ahmedabad Gujarat, India, 380060Rhythm Heart Institute | Vadodara Gujarat, India, 390022K R Hospital | Mysore Karnataka, India, 570001Lisie Hospital | Kochi Kerala, India, 682018Vijan Cardiac & Critical Care | Nashik Maharashtra, India, 422005Vijan Hospital & Research Centre | Nashik Maharashtra, India, 422005G B Pant Institute of Postgraduate Medical Education and Research | New Delhi National Capital Territory of Delhi, India, 110002Max Super Speciality Hospital, Saket | New Delhi National Capital Territory of Delhi, India, 110017Batra Hospital and Medical Research Center | New Delhi National Capital Territory of Delhi, India, 110062VMMC & Safdarjung Hospital | New Dehli New Delhi, India, 110029SP Medical College & A.G.Hospital Bikaner | Bikaner Rajasthan, India, 334003SP Medical College | Bikaner Rajasthan, India, 334003Apollo Hospitals Education & Research Foundation | Chennai Tamil Nadu, India, 600006Gandhi Memorial Hospital- King George's Medical University | Lucknow Uttar Pradesh, India, 226003G B Pant Institute of Postgraduate Medical Education and Res | New Delhi , India, 110002Dr. BL Kapur Memorial Hospital | New Delhi , India, 110005Max Super Speciality Hospital_New Delhi | New Delhi , India, 110017Sir Ganga Ram Hospital | New Delhi , India, 110060Hadassah Ein Karam MC - Cardio Department | Jerusalem , Israel, 91120Western Galilee MC - Cardiology Department | Nahariya , Israel, 22100Rabin MC Beilinson - Heart Failure Unit | Petah Tikva , Israel, 49100Sourasky MC - Cardio Vascular Research Center | Tel Aviv , Israel, 6423906Sheba MC - Cardiology Clinical Research Unit | Tel Litwinsky , Israel, 5265601Spedali Civili Brescia | Brescia Bs, Italy, 25123A.O.U. Ferrara, Sant'Anna | Cona (Ferrara) Fe, Italy, 44124Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII | Bergamo Lombardy, Italy, 24127Centro Cardiologico Monzino | Milan , Italy, 20138Azienda Ospedaliera di Padova - MASTER | Padova , Italy, 35128A.O.U. Policlinico Umberto I | Roma , Italy, 00161Policlinico A. Gemelli IRCCS | Rome , Italy, 00168Hyogo Prefectural HarimaHimeji General Medical Center_Cardiology | Himeji-shi, Hyogo , Japan, 670-8560Kokura Memorial Hospital_Cardiology | Kitakyushu-shi,Fukuoka , Japan, 802-8555Okayama University Hospital_Cardiovascular Medicine | Okayama-shi, Okayama , Japan, 700-8558Omihachiman Community Medical Center_Omihachiman-shi, Siga | Omihachiman-shi, Siga , Japan, 523-0082Osaka City General Hospital_Endocrinology and Diabetes Mellitus | Osaka , Japan, 534-0021Medical Research Institute KITANO HOSPITAL_Cardiovascular Medicine | Osaka-shi, Osaka , Japan, 530-8480Hanaoka Seishu Memorial Hosp._Cardiovascular Medicine | Sapporo-shi, Hokkaido , Japan, 062-0003Tokyo Shinagawa Hospital_Cardiovascular Medicine | Tokyo , Japan, 140-8522Gelre Ziekenhuizen Apeldoorn | Apeldoorn , Netherlands, 7334 DZRijnstate Ziekenhuis | Arnhem , Netherlands, 6815 ADRode Kruis Ziekenhuis Beverwijk | Beverwijk , Netherlands, 1942 LEUMC Groningen | Groningen , Netherlands, 9713 GZSaxenburgh Medisch Centrum | Hardenberg , Netherlands, 7772 SEFrisius MC Leeuwarden | Leeuwarden , Netherlands, 8934 ADBravis Ziekenhuis | Roosendaal , Netherlands, 4708 AEMalopolskie Centrum Sercowo-Naczyniowe | Chrzanów Lesser Poland Voivodeship, Poland, 32-500Uniwersytecki Szpital Kliniczny w Bialymstoku K. Kardio | Bialystok Podlaskie Voivodeship, Poland, 15-276Uniwersytecki Szpital Kliniczny w Bialymstoku K. Kardio | Bialystok Podlaskie Voivodeship, Poland, 15-540Ind. Prak. Lek. w dziedz. Kardiologii lek. med. K. Cymerman | Gdynia Pomeranian Voivodeship, Poland, 81-157Pro Familia Altera Sp. z o.o. | Katowice Silesian Voivodeship, Poland, 40-648I Katedra i Klinika Kardiologii WUM SPCSK | Warsaw , Poland, 02-097Uniwersytecki Szpital Kliniczny nr 2 Uniwersytetu Medycznego w Łodzi | Lodz Łódź Voivodeship, Poland, 90-549Complejo Hospitalario Universitario de Santiago | Santiago de Compostela , Spain, 15706Clínica Nuevas Tecnologías en Diabetes y Endocrinología | Seville , Spain, 41003Hospital Clinico Universitario de Valencia | Valencia , Spain, 46010Dept of Med Sahlgrenska/Östra | Gothenburg , Sweden, 416 50Medicinkliniken Ryhov | Jönköping , Sweden, 551 85Hjärtmottagningen | Uppsala , Sweden, 751 85Ninewells Hospital | Dundee , United Kingdom, DD1 9SYGlasgow Clinical Research Facility | Glasgow , United Kingdom, G31 2ERGlasgow Royal Infirmary | Glasgow , United Kingdom, G31 2ERQueen Elizabeth University Hospital | Glasgow , United Kingdom, G51 4TFWycombe General Hospital | High Wycombe , United Kingdom, HP11 2TTAintree University Hospital | Liverpool , United Kingdom, L9 7ALUniversity Hospital Aintree | Liverpool , United Kingdom, L9 7ALManchester Royal Infirmary_Manchester_0 | Manchester , United Kingdom, M13 9WLManchester Royal Infirmary | Manchester , United Kingdom, M13 9WLGreat Western Hospital | Swindon , United Kingdom, SN3 6BB
Investigators
Study Director: Clinical Transparency (Dept.1452), Novo Nordisk A/S