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Trial · Interventional

CompletedPhase 3Registry data

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

Short name STEP HFpEF DM

NCTNCT04916470 (opens ClinicalTrials.gov in a new tab)Other idEX9536-4773Other idU1111-1257-5069Other id2020-004170-22
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Completed
Phase
Phase 3
Enrollment
617 participants (actual)
Sponsor
Novo Nordisk A/S · Industry
Design
Randomized · Quadruple masking
Countries
16 countries

United States, Argentina, Austria, Canada, Czechia, Germany, Hungary, India, Israel, Italy, Japan, Netherlands, Poland, Spain, Sweden, United Kingdom

Start
15 Jun 2021
Primary completion
11 Oct 2023
Completion
11 Oct 2023
First posted
7 Jun 2021
Last update posted
26 Nov 2025
Conditions
Heart Failure With Preserved Ejection Fraction (HFpEF) and Diabetes Mellitus, Type 2

Timeline

1 trial · 1 completed

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2021202220232024
  1. Ph 3

    STEP HFpEF DM

    NCT04916470

    15 Jun 2021 to 11 Oct 2023

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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. 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.

Interventions

  • SemaglutideDrug
  • Placebo (Semaglutide)Drug

Arms2

  • Experimental

    Semaglutide 2.4 mg once weekly (OW)

    Participants will receive semaglutide injections for 52 weeks.

  • Placebo comparator

    Semaglutide placebo OW

    Participants will receive semaglutide placebo injections for 52 weeks.

Primary outcomes2

Outcomes the sponsor listed as primary.

  1. Change in KCCQ (Kansas City Cardiomyopathy Questionnaire) clinical summary score

    Time frame · From baseline (week 0) to end of treatment (week 52)

    Registry description

    Score on a scale of 0 to 100 where the score 100 means the least burden for the participant.

  2. Change in body weight

    Time frame · From baseline (week 0) to end of treatment (week 52)

    Registry description

    Percentage (%)

Secondary outcomes(20)

  1. Change in 6-minute walking distance

    Time frame · From baseline (week 0) to end of treatment (week 52)

    Registry description

    Measured in metres

  2. Hierarchical composite of time to all-cause death

    Time frame · From baseline (week 0) to end of study (week 57)

    Registry description

    Measured as total wins for each treatment group.

  3. Hierarchical composite of number of heart failure events requiring hospitalisation or urgent heart failure visit

    Time frame · From baseline (week 0) to end of study (week 57)

    Registry description

    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

    Time frame · From baseline (week 0) to end of study (week 57)

    Registry description

    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

    Time frame · From baseline (week 0) to end of study (week 57)

    Registry description

    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

    Time frame · From baseline (week 0) to end of study (week 57)

    Registry description

    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

    Time frame · From baseline (week 0) to end of study (week 57)

    Registry description

    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)

    Time frame · From baseline (week 0) to end of study (week 57)

    Registry description

    Measured as total wins for each treatment group.

  9. Change in C-Reactive Protein

    Time frame · From baseline (week -2) to end of treatment (week 52)

    Registry description

    Presented as ratio to baseline

  10. Participant achieving 10% weight loss or more (Yes/No)

    Time frame · From baseline (week 0) to end of treatment (week 52)

    Registry description

    Count of participants

  11. Participant achieving 15% weight loss or more (Yes/No)

    Time frame · From baseline (week 0) to end of treatment (week 52)

    Registry description

    Count of participants

  12. Participant achieving 20% weight loss or more (Yes/No)

    Time frame · From baseline (week 0) to end of treatment (week 52)

    Registry description

    Count of participants

  13. Participant improving 5 points or more in KCCQ clinical summary score

    Time frame · From baseline (week 0) to end of treatment (week 52)

    Registry description

    Count of participants

  14. Participant improving 10 points or more in KCCQ clinical summary score (Yes/No)

    Time frame · From baseline (week 0) to end of treatment (week 52)

    Registry description

    Count of participants

  15. Change in KCCQ overall summary score

    Time frame · From baseline (week 0) to end of treatment (week 52)

    Registry description

    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

    Time frame · From baseline (week 0) to end of treatment (week 52)

    Registry description

    Count of participants

  17. Participant achieving threshold for clinically meaningful within-subject change in 6MWD

    Time frame · From baseline (week 0) to end of treatment (week 52)

    Registry description

    Count of participants

  18. Change in waist circumference

    Time frame · From baseline (week 0) to end of treatment (visit 52)

    Registry description

    Measured in centimetre (cm)

  19. Change in systolic blood pressure

    Time frame · From baseline (week -2) to end of treatment (week 52)

    Registry description

    Measured in millimetre of mercury (mmHg)

  20. Change in glycated haemoglobin (HbA1c)

    Time frame · From baseline (week 0) to end of treatment (week 52)

    Registry description

    Measured in percentage (%)-point

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

No results are posted for this trial.

Completed trials do not always post results.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies13

Studies that cite this trial.

Studies with results

11 studies on this page

Indexing hint: Randomized controlled trial · 2025

10 results

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.

Davies et al. 2025The lancet. Diabetes & endocrinologycited by 20

PMID 39848268DOI 10.1016/s2213-8587(24)00304-8PUB-39848268

Full text at the publisher10 results
Publisher pageSee results (10)

Indexing hint: Randomized controlled trial · 2025

5 results

Frailty and Effects of Semaglutide in Obesity-Related HFpEF: Findings From the STEP-HFpEF Program.

Pandey et al. 2025JACC. Heart failurecited by 4

PMID 40956259DOI 10.1016/j.jchf.2025.102610PUB-40956259

Full text at the publisher5 results
Publisher pageSee results (5)

Indexing hint: Randomized controlled trial · 2025

9 results

Semaglutide and Exercise Function in Obesity-Related HFpEF: Insights From the STEP-HFpEF Program.

Borlaug et al. 2025JACC. Heart failurecited by 9

PMID 41045908PMC12688318DOI 10.1016/j.jchf.2025.102660PUB-41045908

CC BY9 results
Download PDFSee results (9)

Indexing hint: Randomized controlled trial · 2024

6 results

Semaglutide in Patients with Obesity-Related Heart Failure and Type 2 Diabetes.

Kosiborod et al. 2024The New England journal of medicinecited by 622

PMID 38587233DOI 10.1056/nejmoa2313917PUB-38587233

Full text at the publisher6 results
Publisher pageSee results (6)

Indexing hint: Randomized controlled trial · 2024

7 results

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.

Butler et al. 2024Lancet (London, England)cited by 296

PMID 38599221PMC11317105DOI 10.1016/s0140-6736(24)00469-0PUB-38599221

Rights unknown7 results
Source linkSee results (7)

Indexing hint: Randomized controlled trial · 2024

9 results

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.

Shah et al. 2024European heart journalcited by 68

PMID 38739118PMC11400859DOI 10.1093/eurheartj/ehae322PUB-38739118

CC BY9 results
Download PDFSee results (9)

Indexing hint: Randomized controlled trial · 2024

5 results

Efficacy of Semaglutide by Sex in Obesity-Related Heart Failure With Preserved Ejection Fraction: STEP-HFpEF Trials.

Verma et al. 2024Journal of the American College of Cardiologycited by 48

PMID 38913003DOI 10.1016/j.jacc.2024.06.001PUB-38913003

Full text at the publisher5 results
Publisher pageSee results (5)

Indexing hint: Randomized controlled trial · 2024

8 results

Semaglutide and NYHA Functional Class in Obesity-Related Heart Failure With Preserved Ejection Fraction: The STEP-HFpEF Program.

Schou et al. 2024Journal of the American College of Cardiologycited by 45

PMID 38913004DOI 10.1016/j.jacc.2024.04.038PUB-38913004

Full text at the publisher8 results
Publisher pageSee results (8)

Indexing hint: Randomized controlled trial · 2024

7 results

Inflammation in Obesity-Related HFpEF: The STEP-HFpEF Program.

Verma et al. 2024Journal of the American College of Cardiologycited by 62

PMID 39217564DOI 10.1016/j.jacc.2024.08.028PUB-39217564

Full text at the publisher7 results
Publisher pageSee results (7)

Indexing hint: Randomized controlled trial · 2024

13 results

Atrial Fibrillation and Semaglutide Effects in Obesity-Related Heart Failure With Preserved Ejection Fraction: STEP-HFpEF Program.

Verma et al. 2024Journal of the American College of Cardiologycited by 36

PMID 39217565PMC11486552DOI 10.1016/j.jacc.2024.08.023PUB-39217565

Free to read · publisher termsCC BY-NC-ND13 results
Read at sourceSee results (13)

Indexing hint: Randomized controlled trial · 2024

4 results

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.

Kosiborod et al. 2024Lancet (London, England)cited by 232

PMID 39222642DOI 10.1016/s0140-6736(24)01643-xPUB-39222642

Full text at the publisher4 results
Publisher pageSee results (4)

Indexing hint: Clinical trial · 2023

Design and Baseline Characteristics of STEP-HFpEF Program Evaluating Semaglutide in Patients With Obesity HFpEF Phenotype.

Kosiborod et al. 2023JACC. Heart failurecited by 67

PMID 37294245DOI 10.1016/j.jchf.2023.05.010PUB-37294245

Full text at the publisher
Publisher page

More studies

1 study on this page

Indexing hint: Randomized controlled trial · 2024

Corrected

Effect of Semaglutide on Cardiac Structure and Function in Patients With Obesity-Related Heart Failure.

Solomon et al. 2024Journal of the American College of Cardiologycited by 109

PMID 39217567DOI 10.1016/j.jacc.2024.08.021PUB-39217567

Full text at the publisher
Publisher pageRead the notice

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
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.

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