AzTrials
AzTrials

Heart Failure With Preserved Ejection Fraction (HFpEF) and Diabetes Mellitus, Type 2Phase 3STEP HFpEF DMNCT04916470

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

A Phase 3 study testing Semaglutide in people with Heart Failure With Preserved Ejection Fraction (HFpEF) and Diabetes Mellitus, Type 2, run by Novo Nordisk A/S at 180 sites in 16 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study will look at how participants' daily life is affected by their heart failure. The study will also look at the change in participants' body weight. This study will compare the effect of semaglutide (a new medicine) compared to "dummy" medicine on body weight and heart failure symptoms. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Semaglutide
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
617 participants
Where
180 sitesin 16 countries
Study dates
15 Jun 2021to 11 Oct 2023
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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.

Trial locations and contacts

180 sites in 16 countries.

180 sites in 16 countries

United States54 sites

  • Abington Memorial Hospital

    Abington, Pennsylvania, 19001

  • Endeavor Health Clinical Operations-NCH

    Arlington Heights, Illinois, 60005

  • Ascension Saint Agnes Heart Ca

    Baltimore, Maryland, 21229

  • MedStar Good Samaritan Hosp

    Baltimore, Maryland, 21239

  • John Hopkins Hospital

    Baltimore, Maryland, 21287

  • National Heart Institute Cal

    Beverly Hills, California, 90211

  • Excel Med Ctr Clinical Trials

    Boca Raton, Florida, 33434

  • Grace Research, LLC

    Bossier City, Louisiana, 71111

  • Bay Area Cardiology Associates, P.A.

    Brandon, Florida, 33511

  • Lindner Center,Christ Hospital

    Cincinnati, Ohio, 45219

  • John Muir Physicians Network

    Concord, California, 94520

  • Valley Clinical Trials

    Covina, California, 91723

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75390

  • Cardiology Consultants of Danville Inc.

    Danville, Virginia, 24541

  • Baptist Health Woodland

    Elizabethtown, Kentucky, 42701

  • Endeavor Health Glenbook Hosp

    Evanston, Illinois, 60201

  • Northwestern University_Chicago_0

    Evanston, Illinois, 60208

  • Deaconess Specialty Physicians

    Evansville, Indiana, 47747

  • Eastern Shore Rsrch Inst, LLC

    Fairhope, Alabama, 36532

  • Virginia Heart

    Falls Church, Virginia, 22042

  • Elite Research Center

    Flint, Michigan, 48532

  • OptumCare Clinical Trials LLC

    Golden, Colorado, 80401

  • St Francis Hospital Lindner Research Center

    Greenvale, New York, 11548

  • Heart Clinic of Hammond

    Hammond, Louisiana, 70403

  • Chicago Medical Research LLC

    Hazel Crest, Illinois, 60429

  • Angio Cardiac Care of Texas

    Houston, Texas, 77025

  • Ascension St. Vincent Medical Group

    Indianapolis, Indiana, 46260

  • Univ of Mississippi Med Ctr

    Jackson, Mississippi, 39216

  • Baptist Heart Specialists_Jacksonville

    Jacksonville, Florida, 32258

  • Saint Luke's Hospital of Kansas City

    Kansas City, Missouri, 64111

  • The Research Group of Lexington LLC

    Lexington, Kentucky, 40503

  • Bryan Heart

    Lincoln, Nebraska, 68506

  • Keck Medical Center of USC - Outpatient Clinic

    Los Angeles, California, 90033

  • Baptist Health Louisville

    Louisville, Kentucky, 40207

  • CV Res Ctr of S Florida

    Miami, Florida, 33173

  • Mobile Heart Specialists

    Mobile, Alabama, 36608

  • Clinical Trials of Ame, LLC

    Monroe, Louisiana, 71201

  • Carteret Medical Group

    Morehead City, North Carolina, 28557

  • Cardiovascular Rsrch of NW_IN

    Munster, Indiana, 46321

  • NY Presbyt Hosp-W Cornell Med

    New York, New York, 10021

  • Valley Clinical Trials, Inc.

    Northridge, California, 91325

  • CHI Health Clinic Cardiology (CUMC - Bergan Mercy)

    Omaha, Nebraska, 68124

  • Hospital of University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Virginia Commonwealth University

    Richmond, Virginia, 23219

  • Virginia Commonwealth University

    Richmond, Virginia, 23298-5058

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Grace Research, LLC_Shreveport

    Shreveport, Louisiana, 71105

  • Sanford Health_Sioux Falls

    Sioux Falls, South Dakota, 57117

  • Louisiana Heart Center_Slidell

    Slidell, Louisiana, 70458

  • St Louis Heart & Vascular, P.C.

    St Louis, Missouri, 63136

  • Cotton-O'Neil Heart Center

    Topeka, Kansas, 66606

  • Lundquist Inst-Biomed Innovtn

    Torrance, California, 90502

  • Tennessee Center for Clinical Trials

    Tullahoma, Tennessee, 37388

  • Wake Forest Baptist Health

    Winston-Salem, North Carolina, 27157

Other trials in United States

India19 sites

  • Marengo Asia Health Care Private Limited

    Ahmedabad, Gujarat, 380060

  • SP Medical College & A.G.Hospital Bikaner

    Bikaner, Rajasthan, 334003

  • SP Medical College

    Bikaner, Rajasthan, 334003

  • Apollo Hospitals Education & Research Foundation

    Chennai, Tamil Nadu, 600006

  • Lisie Hospital

    Kochi, Kerala, 682018

  • Gandhi Memorial Hospital- King George's Medical University

    Lucknow, Uttar Pradesh, 226003

  • K R Hospital

    Mysore, Karnataka, 570001

  • Vijan Cardiac & Critical Care

    Nashik, Maharashtra, 422005

  • Vijan Hospital & Research Centre

    Nashik, Maharashtra, 422005

  • VMMC & Safdarjung Hospital

    New Dehli, New Delhi, 110029

  • G B Pant Institute of Postgraduate Medical Education and Research

    New Delhi, National Capital Territory of Delhi, 110002

  • Max Super Speciality Hospital, Saket

    New Delhi, National Capital Territory of Delhi, 110017

  • Batra Hospital and Medical Research Center

    New Delhi, National Capital Territory of Delhi, 110062

  • G B Pant Institute of Postgraduate Medical Education and Res

    New Delhi, 110002

  • Dr. BL Kapur Memorial Hospital

    New Delhi, 110005

  • Max Super Speciality Hospital_New Delhi

    New Delhi, 110017

  • Sir Ganga Ram Hospital

    New Delhi, 110060

  • Krishna Institute of medical sciences Ltd

    Secunderabad, A.P., 500 003

  • Rhythm Heart Institute

    Vadodara, Gujarat, 390022

Other trials in India

Canada14 sites

  • ViaCar Recherche Clinique Inc

    Brossard, Quebec, J4Z 2K9

  • University of Calgary_Calgary

    Calgary, Alberta, T2N 4Z6

  • Cambridge Cardiac Care Centre

    Cambridge, Ontario, N1R 6V6

  • Univ of Alberta Hosp Edmonton

    Edmonton, Alberta, T6G 2B7

  • Applied Med Inf Res

    Montreal, Quebec, H4A 3T2

  • Partnrs Adv Cardio Eval (PACE)

    Newmarket, Ontario, L3Y 2P6

  • North Shore Heart Centre

    North Vancouver, British Columbia, V7M 2H4

  • Oakville Cardiovascular Research LP

    Oakville, Ontario, L6K 3W7

  • Institut universitaire de cardiologie

    Québec, G1V 4G5

  • Heart Health Institute Research, Inc.

    Scarborough Village, Ontario, M1B 4Z8

  • SMH Cardiology Clinical Trials Inc.

    Surrey, British Columbia, V3V 0C6

  • Ctr de Med Metab de Lanaudiere

    Terrebonne, Quebec, J6X 4P7

  • Dr. Louis Yao

    Weston, Ontario, M9N 1W4

  • St. Boniface Hospital

    Winnipeg, Manitoba, R2H 2HA6

Other trials in Canada

Germany10 sites

  • Charité - Campus Virchow-Klinikum - Kardiologie, Angiologie und Intensivmedizin (CRU)

    Berlin, 13353

  • Cardiologicum Dresden und Pirna - MVZ "Am Felsenkeller" (Dresden)

    Dresden, 01277

  • Zentrum für klinische Studien Südbrandenburg GmbH

    Elsterwerda, 04910

  • MVZ CCB Frankfurt und Main-Taunus GbR

    Frankfurt, 60389

  • Medical Center - University Of Freiburg

    Freiburg im Breisgau, 79106

  • Universitätsklinikum Freiburg - Medical Center

    Freiburg im Breisgau, 79106

  • B. Braun Ambulantes Herzzentrum Kassel MVZ GmbH

    Kassel, 34121

  • Universitätsklinikum Leipzig - Klinik und Poliklinik für Kardiologie

    Leipzig, 04103

  • Universitätsmedizin Mainz, Kardiologie I, Studienzentrum

    Mainz, 55131

  • Universitatsklinikum Würzburg - Zentrum für Herzinsuffizienz

    Würzburg, 97078

Other trials in Germany

Hungary10 sites

  • Lausmed Kft.

    Baja, Bács-Kiskun county, 6500

  • Szent Margit Rendelőintézet Nonprofit Kft.

    Budapest, 1032

  • Semmelweis Egyetem Szent Rókus Klinikai Tömb

    Budapest, 1085

  • Gottsegen György Országos Kardiológiai Intézet

    Budapest, 1096

  • Semmelweis Egyetem Városmajori Szív- és Érgyógyászat

    Budapest, 1122

  • Jahn Ferenc Dél-pesti Kórház és Rendelőintézet

    Budapest, 1204

  • DE KK Kardiológiai és Szívsebészeti klinika

    Debrecen, 4032

  • Selye János Kórház

    Komárom, Komárom-Esztergom, 2921

  • Borsod-Abaúj-Zemplén Megyei Központi Kórház

    Miskolc, 3526

  • Zala Megyei Szent Rafael Kórház

    Zalaegerszeg, 8900

Other trials in Hungary

United Kingdom10 sites

  • Ninewells Hospital

    Dundee, DD1 9SY

  • Glasgow Clinical Research Facility

    Glasgow, G31 2ER

  • Glasgow Royal Infirmary

    Glasgow, G31 2ER

  • Queen Elizabeth University Hospital

    Glasgow, G51 4TF

  • Wycombe General Hospital

    High Wycombe, HP11 2TT

  • Aintree University Hospital

    Liverpool, L9 7AL

  • University Hospital Aintree

    Liverpool, L9 7AL

  • Manchester Royal Infirmary_Manchester_0

    Manchester, M13 9WL

  • Manchester Royal Infirmary

    Manchester, M13 9WL

  • Great Western Hospital

    Swindon, SN3 6BB

Other trials in United Kingdom

Argentina9 sites

  • CEMEDIC

    CABA, Buenos Aires, C1440CFD

  • CIPREC Arenales

    CABA, C1061AAS.

  • Centro de Investigación y Prevención Cardiovascular

    CABA, C1119ACN

  • CEMEDIC

    CABA, C1440CFD

  • Cardiología Palermo Duplicate

    Ciudad Autónoma de Buenos Aire, 1425

  • Cardiología Palermo

    Ciudad Autónoma de Buenos Aire, 1425

  • Instituto de Cardiología de Corrientes

    Corrientes, W3400AMZ

  • Consultorio Integral de Atención al Diabético

    Morón, B1708IFF

  • Sanatorio Britanico S.A.

    Rosario, Santa Fe, S2000CVB

Other trials in Argentina

Austria9 sites

  • Krankenhaus St. Josef Braunau

    Braunau am Inn, 5280

  • Medizinische Universität Graz

    Graz, 8036

  • Medizinische Universität Graz

    Graz, A 8036

  • Fließer-Görzer [Ordination]

    Saint Stefan, 8511

  • Medizinische Universität Wien

    Vienna, 1090

  • Klinik Favoriten

    Vienna, 1100

  • Imed 19- privat

    Vienna, 1190

  • AKH Universitätsklinik für Innere Medizin II

    Vienna, A 1090

  • Universitätsklinik für Innere Medizin II

    Vienna, A 1090

Other trials in Austria

Japan8 sites

  • Hyogo Prefectural HarimaHimeji General Medical Center_Cardiology

    Himeji-shi, Hyogo, 670-8560

  • Kokura Memorial Hospital_Cardiology

    Kitakyushu-shi,Fukuoka, 802-8555

  • Okayama University Hospital_Cardiovascular Medicine

    Okayama-shi, Okayama, 700-8558

  • Omihachiman Community Medical Center_Cardiovascular Medicine

    Omihachiman-shi, Siga, 523-0082

  • Osaka City General Hospital

    Osaka, 534-0021

  • Medical Research Institute KITANO HOSPITAL_Cardiovascular Medicine

    Osaka-shi, Osaka, 530-8480

  • Hanaoka Seishu Memorial Hosp._Cardiovascular Medicine

    Sapporo-shi, Hokkaido, 062-0003

  • Tokyo Shinagawa Hospital_Cardiovascular Medicine

    Tokyo, 140-8522

Other trials in Japan

Italy7 sites

  • Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII

    Bergamo, Lombardy, 24127

  • Spedali Civili Brescia

    Brescia, Bs, 25123

  • A.O.U. Ferrara, Sant'Anna

    Cona (Ferrara), Fe, 44124

  • Centro Cardiologico Monzino

    Milan, 20138

  • Azienda Ospedaliera di Padova

    Padova, 35128

  • A.O.U. Policlinico Umberto I

    Roma, 00161

  • Policlinico A. Gemelli IRCCS

    Rome, 00168

Other trials in Italy

Netherlands7 sites

  • Gelre Zkh Apeldoorn

    Apeldoorn, 7334 DZ

  • Rijnstate Ziekenhuis

    Arnhem, 6815 AD

  • Rode Kruis Zkh Beverwijk

    Beverwijk, 1942 LE

  • UMC Groningen

    Groningen, 9713 GZ

  • Saxenburgh MC - Cardiologie

    Hardenberg, 7772 SE

  • Frisius MC Leeuwarden

    Leeuwarden, 8934 AD

  • Bravis Zkh Roosendaal

    Roosendaal, 4708 AE

Other trials in Netherlands

Poland7 sites

  • Uniwersytecki Szpital Kliniczny w Bialymstoku K. Kardio

    Bialystok, Podlaskie Voivodeship, 15-276

  • Uniwersytecki Szpital Kliniczny w Bialymstoku K. Kardio

    Bialystok, Podlaskie Voivodeship, 15-540

  • Malopolskie Centrum Sercowo-Naczyniowe

    Chrzanów, Lesser Poland Voivodeship, 32-500

  • Ind. Spec. Prak. Lek. w dziedz. Kardiologii lek. med. K. Cymerman

    Gdynia, Pomeranian Voivodeship, 81-157

  • Pro Familia Altera Sp. z o.o.

    Katowice, Silesian Voivodeship, 40-648

  • Uniwersytecki Szpital Kliniczny nr 2 Uniwersytetu Medycznego w Lodzi

    Lodz, Łódź Voivodeship, 90-549

  • I Katedra i Klinika Kardiologii WUM SPCSK

    Warsaw, 02-097

Other trials in Poland

Czechia5 sites

  • Edumed Broumov

    Broumov, 550 01

  • Fakultní poliklinika VFN ambulance Srdecniho selhani

    Prague, 120 00

  • IKEM

    Prague, 140 21

  • MEDICON a.s.

    Prague, 170 00

  • Poliklinika Holešovice VISIONARY - Medicon Pharm s.r.o.

    Prague, 170 00

Other trials in Czechia

Israel5 sites

  • Hadassah Ein Karam MC - Cardio Department

    Jerusalem, 91120

  • Western Galilee MC - Cardiology Department

    Nahariya, 22100

  • Rabin MC Beilinson - Heart Failure Unit

    Petah Tikva, 49100

  • Sourasky MC - Cardio Vascular Research Center

    Tel Aviv, 6423906

  • Sheba MC - Cardiology Clinical Research Unit

    Tel HaShomer, 5265601

Other trials in Israel

Spain3 sites

  • Complejo Hospitalario Universitario de Santiago

    Santiago de Compostela, 15706

  • Clínica Nuevas Tecnologías en Diabetes y Endocrinología

    Seville, 41003

  • Hospital Clinico Universitario de Valencia

    Valencia, 46010

Other trials in Spain

Sweden3 sites

  • Sahlgrenska US - Medicinkliniken

    Gothenburg, 416 50

  • Medicinkliniken Ryhov

    Jönköping, 551 85

  • Uppsala US - Hjärtmottagningen

    Uppsala, 751 85

Other trials in Sweden

About this study

Official title: Effect 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

This study will look at how participants' daily life is affected by their heart failure. The study will also look at the change in participants' body weight.

This study will compare the effect of semaglutide (a new medicine) compared to "dummy" medicine on body weight and heart failure symptoms.

Read more

Participants will either get semaglutide or "dummy" medicine, which treatment participants get is decided by chance.

Participants will need to take 1 injection once a week. The study medicine is injected with a thin needle in a skin fold in the stomach area, thigh or upper arm.

During the study participants will have talks with the study staff about healthy lifestyle and physical activity.

The study will last for about 59 weeks, that is a little more than 1 year. Participants will have 12 clinic visits with the study doctor.

  • At 6 of the visits participants will have blood samples taken.
  • At 5 of the visits participants will be asked to fill in a questionnaire
  • At 4 of the visits participants will have to do a 6-minute walking test
  • At 3 of the visits participants will have a test to check the heart.
  • participants will have their eyes checked before or at the start of the study and at the end of the study

Women cannot take part if pregnant, breast-feeding or plan to become pregnant during the study period.

Being tested
Semaglutide, Placebo (Semaglutide)
Medical subject headings
Diabetes Mellitus

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SemaglutideDrug

    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.

  • Placebo (Semaglutide)Drug

    Participants will receive semaglutide matching placebo s.c. injection(s) once-weekly for 52 weeks.

Study groups in NCT04916470
Study groupRoleWhat they receive
Semaglutide 2.4 mg once weekly (OW)ExperimentalParticipants will receive semaglutide injections for 52 weeks.
Receives: Drug: Semaglutide
Semaglutide placebo OWPlacebo comparatorParticipants will receive semaglutide placebo injections for 52 weeks.
Receives: Drug: Placebo (Semaglutide)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in KCCQ (Kansas City Cardiomyopathy Questionnaire) Clinical Summary Score

    Change in KCCQ-Clinical Summary Score (CSS) from baseline (week 0) to end of treatment (week 52) is presented. The KCCQ is a standardised 23-item, self-administered instrument that quantifies heart failure symptoms (frequency, severity, and recent change), physical limitation, quality of life (QOL), and social limitation. Scores were transformed to a range of 0 to 100 in which higher scores reflected better health status. KCCQ-Clinical Summary Score (CSS) included the symptom and physical limitation domains of the KCCQ. The outcome data was evaluated based on the in-trial observation period. The in-trial period was defined as the time interval from date of randomisation to date of last contact with trial site (or date of withdrawal of informed consent or death).

    Measured: Baseline (week 0), end of treatment (week 52)

  2. Percentage Change in Body Weight

    Percentage change in body weight from baseline (week 0) to end of treatment (week 52) is presented. The outcome data was evaluated based on the in-trial observation period. The in-trial period was defined as the time interval from date of randomisation to date of last contact with trial site (or date of withdrawal of informed consent or death).

    Measured: Baseline (week 0), end of treatment (week 52)

Secondary outcomes (15)

  1. Change in Six-minute Walking Distance

    Change in six-minute walking distance from baseline (week 0) to end of treatment (week 52) is presented. The 6 Minute Walk Test is a direct and timed measure of walk distance. The goal is for the subject to walk as far as possible in six minutes without running. The outcome data was evaluated based on the in-trial observation period. The in-trial period was defined as the time interval from date of randomisation to date of last contact with trial site (or date of withdrawal of informed consent or death).

    Measured: Baseline (week 0), end of treatment (week 52)

  2. Hierarchical Composite Endpoint: Total Number of Wins for Each Treatment Group

    Hierarchical composite outcome measure from baseline (week 0) to end of trial (week 57) is presented. Analysis of the hierarchical composite endpoint was based on direct comparisons of each participant randomised to semaglutide 2.4 mg and placebo within each stratum. A 'treatment winner' (1000 imputations) based on similar observation time was declared based on endpoint hierarchy. Outcome data was evaluated based on in-trial observation period which was defined as time interval from date of randomisation to date of last contact with trial site (or date of withdrawal of informed consent or death). Missing observations at week 52 for KCCQ-CSS and body weight were multiple (x1000) imputed (by MAR assumption) using available measurements at week 52 from participants of same randomized treatment arm. Missing observations due to CV death or previous HF event were single imputed using change from baseline to overall lowest KCCQ-CSS value across treatment arms and time points.

    Measured: Baseline (week 0), end of trial (week 57)

  3. Change in C-Reactive Protein

    Change in C-Reactive Protein from baseline (week -2) to end of treatment (week 52) is presented. The outcome data was evaluated based on the in-trial observation period. The in-trial period was defined as the time interval from date of randomisation to date of last contact with trial site (or date of withdrawal of informed consent or death).

    Measured: From baseline (week -2) to end of treatment (week 52)

  4. Participants Achieving 10% Weight Loss or More (Yes/No)

    Participants achieving 10% weight loss or more (Yes/No) at week 52 is presented. In the reported data, 'Yes' infers number of participants who have achieved 10% weight loss or more whereas 'No' infers number of participants who have not achieved 10% weight loss or more. The outcome data was evaluated based on the in-trial observation period. The in-trial period was defined as the time interval from date of randomisation to date of last contact with trial site (or date of withdrawal of informed consent or death).

    Measured: At Week 52

  5. Participants Achieving 15% Weight Loss or More (Yes/No)

    Participants achieving 15% weight loss or more (Yes/No) at week 52 is presented. In the reported data, 'Yes' infers number of participants who have achieved 15% weight loss or more whereas 'No' infers number of participants who have not achieved 15% weight loss or more. The outcome data was evaluated based on the in-trial observation period. The in-trial period was defined as the time interval from date of randomisation to date of last contact with trial site (or date of withdrawal of informed consent or death).

    Measured: At Week 52

  6. Participants Achieving 20% Weight Loss or More (Yes/No)

    Participants achieving 20% weight loss or more (Yes/No) at week 52 is presented. In the reported data, 'Yes' infers number of participants who have achieved 20% weight loss or more whereas 'No' infers number of participants who have not achieved 20% weight loss or more. The outcome data was evaluated based on the in-trial observation period. The in-trial period was defined as the time interval from date of randomisation to date of last contact with trial site (or date of withdrawal of informed consent or death).

    Measured: At Week 52

  7. Participants Improving 5 Points or More in KCCQ Clinical Summary Score (Yes/No)

    Participants improving 5 points or more in KCCQ clinical summary score (Yes/No) at week 52 is presented. The KCCQ is a standardised 23-item, self-administered instrument that quantifies heart failure symptoms (frequency, severity, and recent change), physical limitation, quality of life (QOL), and social limitation. Scores were transformed to a range of 0 to 100 in which higher scores reflected better health status. KCCQ-CSS included the symptom and physical limitation domains of the KCCQ. In the reported data, 'Yes' infers number of participants who have improved 5 points or more in score whereas 'No' infers number of participants who have not improved 5 points or more in score. The outcome data was evaluated based on the in-trial observation period. The in-trial period was defined as the time interval from date of randomisation to date of last contact with trial site (or date of withdrawal of informed consent or death).

    Measured: At Week 52

  8. Participants Improving 10 Points or More in KCCQ Clinical Summary Score (Yes/No)

    Participants improving 10 points or more in KCCQ clinical summary score (Yes/No) at week 52 is presented. The KCCQ is a standardised 23-item, self-administered instrument that quantifies heart failure symptoms (frequency, severity, and recent change), physical limitation, quality of life (QOL), and social limitation. Scores were transformed to a range of 0 to 100 in which higher scores reflected better health status. KCCQ-CSS included the symptom and physical limitation domains of the KCCQ. In reported data, 'Yes' infers number of participants who have improved 10 points or more in score whereas 'No' infers number of participants who have not improved 10 points or more in score. The outcome data was evaluated based on the in-trial observation period. The in-trial period was defined as the time interval from date of randomisation to date of last contact with trial site (or date of withdrawal of informed consent or death).

    Measured: At Week 52

  9. Change in KCCQ Overall Summary Score

    Change in KCCQ overall summary score from baseline (week 0) to end of treatment (week 52) is presented. The KCCQ is a standardised 23-item, self-administered instrument that quantifies heart failure symptoms (frequency, severity, and recent change), physical limitation, QOL, and social limitation. Scores are transformed to a range of 0 to 100 in which higher scores reflect better health status. KCCQ- overall summary score (OSS) included the symptom, physical limitation, quality of life, and social limitation domains. The outcome data was evaluated based on the in-trial observation period. The in-trial period was defined as the time interval from date of randomisation to date of last contact with trial site (or date of withdrawal of informed consent or death).

    Measured: Baseline (week 0), end of treatment (week 52)

  10. Participants Achieving Threshold for Clinically Meaningful Within-participant Change in KCCQ-CSS (PGI-S)

    Participants achieving threshold for clinically meaningful within-participant change (based on participant perspective) in KCCQ-CSS (Patient Global Impression of Status [PGI-S]) at week 52 is presented. KCCQ is a standardised 23-item instrument that quantifies heart failure symptoms (frequency, severity, and recent change), physical limitation, QOL, and social limitation. Scores are transformed to a range of 0 to 100 where higher scores reflect better health status. KCCQ-CSS includes the symptom and physical limitation domains of KCCQ. PGI-S for KCCQ was used to rate participants' symptoms of heart failure in last two weeks using a 4-category ordinal scale (no symptoms, mild, moderate, severe). The threshold of 16.3 points is based on PGI-S for KCCQ-CSS. Outcome data was evaluated based on in-trial period. In-trial period was defined as time interval from date of randomisation to date of last contact with trial site (or date of withdrawal of informed consent or death).

    Measured: At Week 52

  11. Participants Achieving Threshold for Clinically Meaningful Within-participant Change in Six Minute Walking Distance (6MWD) (PGI-S)

    Participants achieving threshold for clinically meaningful within-participant change in 6MWD (PGI-S) at week 52 is presented. The six minute walk test (6MWT) is a direct and timed measure of walk distance. The goal is for the subject to walk as far as possible in six minutes without running. The PGI-S for 6MWT was used to rate any difficulty that participants were experiencing in walking quickly using a 5-category ordinal scale (not at all difficult, a little difficult, moderately difficult, very difficult, or unable to walk quickly). The threshold of 16.2 meters is based on PGI-S for 6MWT. The outcome data was evaluated based on the in-trial observation period. The in-trial period was defined as the time interval from date of randomisation to date of last contact with trial site (or date of withdrawal of informed consent or death).

    Measured: At Week 52

  12. Change in Waist Circumference

    Change in waist circumference from baseline (week 0) to end of treatment (week 52) is presented. The outcome data was evaluated based on the in-trial observation period. The in-trial period was defined as the time interval from date of randomisation to date of last contact with trial site (or date of withdrawal of informed consent or death).

    Measured: From baseline (week 0) to end of treatment (week 52)

  13. Change in Systolic Blood Pressure

    Change in systolic blood pressure from baseline (week -2) to end of treatment (week 52) is presented. The outcome data was evaluated based on the in-trial observation period. The in-trial period was defined as the time interval from date of randomisation to date of last contact with trial site (or date of withdrawal of informed consent or death).

    Measured: Bseline (week -2), end of treatment (week 52)

  14. Change in Glycated Haemoglobin (HbA1c)

    Change in HbA1c from baseline (week 0) to end of treatment (week 52) is presented. The outcome data was evaluated based on the in-trial observation period. The in-trial period was defined as the time interval from date of randomisation to date of last contact with trial site (or date of withdrawal of informed consent or death).

    Measured: Baseline (week 0), end of treatment (week 52)

  15. Number of Treatment Emergent Severe or Clinically Significant Hypoglycaemia Episodes

    Number of treatment emergent severe or clinically significant hypoglycaemia episodes from baseline (week 0) to end of trial (week 57) is presented. Clinically significant hypoglycemic episode is defined as blood glucose concentration of less than 54 milligrams per deciliter (mg/dL) which is sufficiently low to indicate serious, clinically important hypoglycaemia. Severe hypoglycemic episode is defined as hypoglycaemia associated with severe cognitive impairment requiring external assistance for recovery. The outcome data was evaluated based on on-treatment period. A time-point was considered as 'on-treatment' if any dose of trial product had been administered within the prior 5 weeks (35 days).

    Measured: From baseline (week 0) to end of trial (week 57)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Jun 2021
  2. Study start15 Jun 2021
  3. Primary completion11 Oct 2023
  4. Study completion11 Oct 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
617 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04916470
Sponsor's protocol ID
EX9536-4773
Other IDs
U1111-1257-5069, 2020-004170-22
Acronym
STEP HFpEF DM
Status last verified
Oct 2026
First submitted
1 Jun 2021
Last updated
2 Nov 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Publications

  • Kosiborod MN, Abildstrom SZ, Borlaug BA, Butler J, Christensen L, Davies M, Hovingh KG, Kitzman DW, Lindegaard ML, Moller DV, Shah SJ, Treppendahl MB, Verma S, Petrie MC. Design and Baseline Characteristics of STEP-HFpEF Program Evaluating Semaglutide in Patients With Obesity HFpEF Phenotype. JACC Heart Fail. 2023 Aug;11(8 Pt 1):1000-1010. doi: 10.1016/j.jchf.2023.05.010. Epub 2023 May 21.

    PubMed 37294245

  • Borlaug BA, Kitzman DW, Patel S, Chinnakondepalli KM, Butler J, Davies MJ, Petrie MC, Shah SJ, Verma S, Nunez J, Einfeldt MN, Liisberg K, Salsali A, Kosiborod MN; STEP-HFpEF Trial Committees and Investigators. Semaglutide and Exercise Function in Obesity-Related HFpEF: Insights From the STEP-HFpEF Program. JACC Heart Fail. 2025 Nov;13(11):102660. doi: 10.1016/j.jchf.2025.102660. Epub 2025 Oct 3.

    PubMed 41045908

  • Pandey A, Kitzman DW, Chinnakondepalli KM, Patel S, Borlaug BA, Butler J, Davies MJ, Shah SJ, Verma S, Ronnback C, Domdey A, Liisberg K, Schou M, Perna E, Ahmed FZ, Fu M, Petrie MC, Kosiborod MN. Frailty and Effects of Semaglutide in Obesity-Related HFpEF: Findings From the STEP-HFpEF Program. JACC Heart Fail. 2025 Oct;13(10):102610. doi: 10.1016/j.jchf.2025.102610. Epub 2025 Sep 15.

    PubMed 40956259

  • Davies MJ, van der Meer P, Verma S, Patel S, Chinnakondepalli KM, Borlaug BA, Butler J, Kitzman DW, Shah SJ, Harring S, Salsali A, Rasmussen S, von Lewinski D, Abhayaratna W, Petrie MC, Kosiborod MN; STEP-HFpEF Trials Committees and Investigators. Semaglutide in obesity-related heart failure with preserved ejection fraction and type 2 diabetes across baseline HbA1c levels (STEP-HFpEF DM): a prespecified analysis of heart failure and metabolic outcomes from a randomised, placebo-controlled trial. Lancet Diabetes Endocrinol. 2025 Mar;13(3):196-209. doi: 10.1016/S2213-8587(24)00304-8. Epub 2025 Jan 20.

    PubMed 39848268

  • Kosiborod MN, Deanfield J, Pratley R, Borlaug BA, Butler J, Davies MJ, Emerson SS, Kahn SE, Kitzman DW, Lingvay I, Mahaffey KW, Petrie MC, Plutzky J, Rasmussen S, Ronnback C, Shah SJ, Verma S, Weeke PE, Lincoff AM; SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM Trial Committees and Investigators. Semaglutide versus placebo in patients with heart failure and mildly reduced or preserved ejection fraction: a pooled analysis of the SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM randomised trials. Lancet. 2024 Sep 7;404(10456):949-961. doi: 10.1016/S0140-6736(24)01643-X. Epub 2024 Aug 30.

    PubMed 39222642

  • Solomon SD, Ostrominski JW, Wang X, Shah SJ, Borlaug BA, Butler J, Davies MJ, Kitzman DW, Verma S, Abildstrom SZ, Nygaard Einfeldt M, Rasmussen S, Abhayaratna WP, Ahmed FZ, Ben-Gal T, Chopra V, Ito H, Merkely B, Nunez J, Senni M, van der Meer P, Wolf D, Petrie MC, Kosiborod MN; STEP-HFpEF Trial Committees and Investigators. Effect of Semaglutide on Cardiac Structure and Function in Patients With Obesity-Related Heart Failure. J Am Coll Cardiol. 2024 Oct 22;84(17):1587-1602. doi: 10.1016/j.jacc.2024.08.021. Epub 2024 Aug 30.

    PubMed 39217567

  • Verma S, Butler J, Borlaug BA, Davies MJ, Kitzman DW, Petrie MC, Shah SJ, Jensen TJ, Rasmussen S, Ronnback C, Merkely B, O'Keefe E, Kosiborod MN; STEP-HFpEF and STEP-HFpEF DM Investigators. Atrial Fibrillation and Semaglutide Effects in Obesity-Related Heart Failure With Preserved Ejection Fraction: STEP-HFpEF Program. J Am Coll Cardiol. 2024 Oct 22;84(17):1603-1614. doi: 10.1016/j.jacc.2024.08.023. Epub 2024 Aug 30.

    PubMed 39217565

  • Verma S, Petrie MC, Borlaug BA, Butler J, Davies MJ, Kitzman DW, Shah SJ, Ronnback C, Abildstrom SZ, Liisberg K, Wolf D, von Lewinski D, Lelonek M, Melenovsky V, Senni M, Kosiborod MN; STEP-HFpEF Trial Committees and Investigators. Inflammation in Obesity-Related HFpEF: The STEP-HFpEF Program. J Am Coll Cardiol. 2024 Oct 22;84(17):1646-1662. doi: 10.1016/j.jacc.2024.08.028. Epub 2024 Aug 30.

    PubMed 39217564

  • Schou M, Petrie MC, Borlaug BA, Butler J, Davies MJ, Kitzman DW, Shah SJ, Verma S, Patel S, Chinnakondepalli KM, Harring S, Abildstrom SZ, Liisberg K, Kosiborod MN; STEP-HFpEF Trial Committees and Investigators. Semaglutide and NYHA Functional Class in Obesity-Related Heart Failure With Preserved Ejection Fraction: The STEP-HFpEF Program. J Am Coll Cardiol. 2024 Jul 16;84(3):247-257. doi: 10.1016/j.jacc.2024.04.038. Epub 2024 Jun 23.

    PubMed 38913004

  • Verma S, Butler J, Borlaug BA, Davies M, Kitzman DW, Shah SJ, Petrie MC, Barros E, Ronnback C, Vestergaard LS, Schou M, Ezekowitz JA, Sharma K, Patel S, Chinnakondepalli KM, Kosiborod MN; STEP-HFpEF Trial Committees and Investigators. Efficacy of Semaglutide by Sex in Obesity-Related Heart Failure With Preserved Ejection Fraction: STEP-HFpEF Trials. J Am Coll Cardiol. 2024 Aug 27;84(9):773-785. doi: 10.1016/j.jacc.2024.06.001. Epub 2024 Jun 23.

    PubMed 38913003

  • Shah SJ, Sharma K, Borlaug BA, Butler J, Davies M, Kitzman DW, Petrie MC, Verma S, Patel S, Chinnakondepalli KM, Einfeldt MN, Jensen TJ, Rasmussen S, Asleh R, Ben-Gal T, Kosiborod MN. Semaglutide and diuretic use in obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF-DM trials. Eur Heart J. 2024 Sep 14;45(35):3254-3269. doi: 10.1093/eurheartj/ehae322.

    PubMed 38739118

  • Butler J, Shah SJ, Petrie MC, Borlaug BA, Abildstrom SZ, Davies MJ, Hovingh GK, Kitzman DW, Moller DV, Verma S, Einfeldt MN, Lindegaard ML, Rasmussen S, Abhayaratna W, Ahmed FZ, Ben-Gal T, Chopra V, Ezekowitz JA, Fu M, Ito H, Lelonek M, Melenovsky V, Merkely B, Nunez J, Perna E, Schou M, Senni M, Sharma K, van der Meer P, Von Lewinski D, Wolf D, Kosiborod MN; STEP-HFpEF Trial Committees and Investigators. Semaglutide versus placebo in people with obesity-related heart failure with preserved ejection fraction: a pooled analysis of the STEP-HFpEF and STEP-HFpEF DM randomised trials. Lancet. 2024 Apr 27;403(10437):1635-1648. doi: 10.1016/S0140-6736(24)00469-0. Epub 2024 Apr 7.

    PubMed 38599221

  • Kosiborod MN, Petrie MC, Borlaug BA, Butler J, Davies MJ, Hovingh GK, Kitzman DW, Moller DV, Treppendahl MB, Verma S, Jensen TJ, Liisberg K, Lindegaard ML, Abhayaratna W, Ahmed FZ, Ben-Gal T, Chopra V, Ezekowitz JA, Fu M, Ito H, Lelonek M, Melenovsky V, Merkely B, Nunez J, Perna E, Schou M, Senni M, Sharma K, van der Meer P, Von Lewinski D, Wolf D, Shah SJ; STEP-HFpEF DM Trial Committees and Investigators. Semaglutide in Patients with Obesity-Related Heart Failure and Type 2 Diabetes. N Engl J Med. 2024 Apr 18;390(15):1394-1407. doi: 10.1056/NEJMoa2313917. Epub 2024 Apr 6.

    PubMed 38587233

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Semaglutide in people with Heart Failure With Preserved Ejection Fraction (HFpEF) and Diabetes Mellitus, Type 2, run by Novo Nordisk A/S at 180 sites in 16 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 180 sites in United States, India, Canada, Germany, Hungary and 11 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 2 Nov 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in KCCQ (Kansas City Cardiomyopathy Questionnaire) Clinical Summary Score (time frame: Baseline (week 0), end of treatment (week 52)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04916470, which also lists 13 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2026.

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