STEP-HFpEF

CompletedPhase 3Results posted

Research Study to Investigate How Well Semaglutide Works in People Living With Heart Failure and Obesity

Effect of Semaglutide 2.4 mg Once Weekly on Function and Symptoms in Subjects With Obesity-related Heart Failure With Preserved Ejection Fraction

Lead sponsor

Novo Nordisk A/S

Asset

Semaglutide

Subcutaneous · GLP-1 agonist

Listed sites

146

Recruiting sites

—

Enrollment

529

actual

Study population

Heart failure, Obesity / overweight

Key I/E criteria

•BMI ≥30•EF ≥45%

Primary endpoints

•KCCQ clinical summary•Body weight, % change•Body weight, absolute change (kg)

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT04788511

Org study IDEX9536-4665

Secondary ID2019-004452-11European Medicines Agency (EudraCT)

Secondary IDU1111-1243-4358World Health Organization (WHO)

Timeline

Milestones

Study first posted2021-03-09actual

Study start2021-03-16actual

Primary completion2023-04-18actual

Study completion2023-04-18actual

Results first posted2024-06-11actual

Last update posted2025-12-05actual

Assets

Investigational agents

Semaglutide

Study populations

Who this study enrolls

Heart failureObesity / overweight

Eligibility

Who can enroll

Minimum age18 Years

SexAll

Healthy volunteersNot accepted

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 percentage at screening

Exclusion criteria

•A self-reported change in body weight greater than 5 kg (11 lbs) within 90 days before screening irrespective of medical records

•Haemoglobin A1c (HbA1c) greater than or equal to 6.5 percentage (48 mmol/mol) based on latest available value from medical records, no older than 3 months or if unavailable a local measurement at screening

Endpoints (30)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Heart failure

Weight & body composition

Cardiometabolic biomarkers

Weight & body composition

10 endpoints

Primary/registry result

Change in Body Weight

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

Body weight, % change

percent change from baseline, improvement

Posted result

Group	Value (mean), Percentage of body weight	95% CI
Semaglutide 2.4 mg	-13.9	—
Placebo	-2.5	—

Estimated Treatment Difference-10.795% CI-11.9 – -9.4p<0.0001ANCOVA

Primary/protocol endpoint

Change in Body Weight

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

Body weight, absolute change (kg)

change from baseline, improvement

Secondary/registry result

Percentage of Participants Achieving 10 Percent (%) Weight Loss (Yes/No)

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

≥10% weight-loss responders

threshold achievement, improvement

Posted result

Group	Value (number), Percentage of participants	95% CI
Semaglutide 2.4 mgNo	34.1	—
Yes	65.9	—
PlaceboNo	90.5	—
Yes	9.5	—

Secondary/registry result

Percentage of Participants Achieving 15% Weight Loss (Yes/No)

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

≥15% weight-loss responders

threshold achievement, improvement

Posted result

Group	Value (number), Percentage of participants	95% CI
Semaglutide 2.4 mgNo	56.1	—
Yes	43.9	—
PlaceboNo	97.9	—
Yes	2.1	—

Secondary/registry result

Percentage of Participants Achieving 20% Weight Loss (Yes/No)

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

≥20% weight-loss responders

threshold achievement, improvement

Posted result

Group	Value (number), Percentage of participants	95% CI
Semaglutide 2.4 mgNo	76.4	—
Yes	23.6	—
PlaceboNo	99.6	—
Yes	0.4	—

Secondary/registry result

Change in Waist Circumference

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

Waist circumference, change

change from baseline, improvement

Posted result

Group	Value (mean), Centimeter	95% CI
Semaglutide 2.4 mg	-12.0	—
Placebo	-2.8	—

Secondary/protocol endpoint

Percentage of Participants Achieving 10 Percent (%) Weight Loss (Yes/No)

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

≥10% weight-loss responders

threshold achievement, improvement

Secondary/protocol endpoint

Percentage of Participants Achieving 15% Weight Loss (Yes/No)

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

≥15% weight-loss responders

threshold achievement, improvement

Secondary/protocol endpoint

Percentage of Participants Achieving 20% Weight Loss (Yes/No)

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

≥20% weight-loss responders

threshold achievement, improvement

Secondary/protocol endpoint

Change in Waist Circumference

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

Waist circumference, change

change from baseline, improvement

Heart failure

16 endpoints

Primary/registry result

Change in Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS)

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

KCCQ clinical summary

change from baseline, improvement

Posted result

Group	Value (mean), Score on a scale	95% CI
Semaglutide 2.4 mg	16.8	—
Placebo	10.3	—

Estimated Treatment Difference7.895% CI4.8 – 10.9p<0.0001ANCOVA

Primary/protocol endpoint

Change in Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS)

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

KCCQ clinical summary

change from baseline, improvement

Secondary/registry result

Change in Six-minute Walking Distance (6MWD)

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

6-minute walk distance

change from baseline, improvement

Posted result

Group	Value (mean), Meters	95% CI
Semaglutide 2.4 mg	23.5	—
Placebo	5.8	—

Secondary/registry result

The Hierarchical Composite Endpoint: Percentage of Wins of Participant Pairs

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

Heart-failure composite

composite event, event

componentsAll-cause death, Heart-failure hospitalization, Urgent heart-failure visit, KCCQ clinical summary, 6-minute walk distance

Posted result

Group	Value (number), Percentages of wins of participant pairs	95% CI
Semaglutide 2.4 mg	60.1	—
Placebo	34.9	—

Secondary/registry result

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

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

KCCQ clinical summary

threshold achievement, improvement

Posted result

Group	Value (number), Percentage of participants	95% CI
Semaglutide 2.4 mgNo	24.7	—
Yes	75.3	—
PlaceboNo	36.3	—
Yes	63.7	—

Secondary/registry result

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

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

KCCQ clinical summary

threshold achievement, improvement

Posted result

Group	Value (number), Percentage of participants	95% CI
Semaglutide 2.4 mgNo	36.6	—
Yes	63.4	—
PlaceboNo	51.5	—
Yes	48.5	—

Secondary/registry result

Change in KCCQ Overall Summary Score (KCCQ-OSS)

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

KCCQ total score

change from baseline, improvement

Posted result

Group	Value (mean), Score on a scale	95% CI
Semaglutide 2.4 mg	16.8	—
Placebo	10.9	—

Secondary/registry result

Percentage of Participants Achieving Threshold for Clinically Meaningful Within-participants Change in KCCQ-CSS (PGI-S)

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

KCCQ clinical summary

threshold achievement, improvement

Posted result

Group	Value (number), Percentage of Participants	95% CI
Semaglutide 2.4 mg	43.2	—
Placebo	32.5	—

Secondary/registry result

Percentage of Participants Achieving Threshold for Clinically Meaningful Within-participants Change in 6MWD (PGI-S)

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

6-minute walk distance

threshold achievement, improvement

Posted result

Group	Value (number), Percentage of Participants	95% CI
Semaglutide 2.4 mg	42.5	—
Placebo	28.0	—

Secondary/protocol endpoint

Change in Six-minute Walking Distance (6MWD)

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

6-minute walk distance

change from baseline, improvement

Secondary/protocol endpoint

The Hierarchical Composite Endpoint: Percentage of Wins of Participant Pairs

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

Heart-failure composite

composite event, event

componentsAll-cause death, Heart-failure hospitalization, Urgent heart-failure visit, KCCQ clinical summary, 6-minute walk distance

Secondary/protocol endpoint

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

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

KCCQ clinical summary

threshold achievement, improvement

Secondary/protocol endpoint

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

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

KCCQ clinical summary

threshold achievement, improvement

Secondary/protocol endpoint

Change in KCCQ Overall Summary Score (KCCQ-OSS)

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

KCCQ total score

change from baseline, improvement

Secondary/protocol endpoint

Percentage of Participants Achieving Threshold for Clinically Meaningful Within-participants Change in KCCQ-CSS (PGI-S)

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

KCCQ clinical summary

threshold achievement, improvement

Secondary/protocol endpoint

Percentage of Participants Achieving Threshold for Clinically Meaningful Within-participants Change in 6MWD (PGI-S)

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

6-minute walk distance

threshold achievement, improvement

Cardiometabolic biomarkers

4 endpoints

Secondary/registry result

Change in C-Reactive Protein (CRP): Ratio to Baseline

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

hs-CRP, change

ratio, improvement

LOINC 30522-7

Posted result

Group	Value (geometric_mean), Ratio of C-reactive protein	95% CI
Semaglutide 2.4 mg	0.55	—
Placebo	0.92	—

Secondary/registry result

Change in Systolic Blood Pressure (SBP)

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

Systolic BP, change

change from baseline, improvement

LOINC 8480-6

Posted result

Group	Value (mean), millimetre of mercury (mmHg)	95% CI
Semaglutide 2.4 mg	-6.4	—
Placebo	-1.1	—

Secondary/protocol endpoint

Change in C-Reactive Protein (CRP): Ratio to Baseline

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

hs-CRP, change

ratio, improvement

LOINC 30522-7

Secondary/protocol endpoint

Change in Systolic Blood Pressure (SBP)

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

Systolic BP, change

change from baseline, improvement

LOINC 8480-6

Publications (15)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Semaglutide and Exercise Function in Obesity-Related HFpEF: Insights From the STEP-HFpEF Program.
JACC. Heart failure2025 Nov (month)PMID41045908doi:10.1016/j.jchf.2025.102660via pubmed nct search
Frailty and Effects of Semaglutide in Obesity-Related HFpEF: Findings From the STEP-HFpEF Program.
JACC. Heart failure2025 Oct (month)PMID40956259doi:10.1016/j.jchf.2025.102610via pubmed nct search
Inflammation in Obesity-Related HFpEF: The STEP-HFpEF Program.
Journal of the American College of Cardiology2024 Oct 22PMID39217564doi:10.1016/j.jacc.2024.08.028via pubmed nct search
Atrial Fibrillation and Semaglutide Effects in Obesity-Related Heart Failure With Preserved Ejection Fraction: STEP-HFpEF Program.
Journal of the American College of Cardiology2024 Oct 22PMID39217565doi:10.1016/j.jacc.2024.08.023via pubmed nct search
Effect of Semaglutide on Cardiac Structure and Function in Patients With Obesity-Related Heart Failure.
Journal of the American College of Cardiology2024 Oct 22PMID39217567doi:10.1016/j.jacc.2024.08.021via pubmed nct search
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.
European heart journal2024 Sep 14PMID38739118doi:10.1093/eurheartj/ehae322via clinicaltrials gov reference derived + pubmed nct search
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 (London, England)2024 Sep 7PMID39222642doi:10.1016/S0140-6736(24)01643-Xvia clinicaltrials gov reference derived + pubmed nct search
Efficacy of Semaglutide by Sex in Obesity-Related Heart Failure With Preserved Ejection Fraction: STEP-HFpEF Trials.
Journal of the American College of Cardiology2024 Aug 27PMID38913003doi:10.1016/j.jacc.2024.06.001via pubmed nct search
Semaglutide and NYHA Functional Class in Obesity-Related Heart Failure With Preserved Ejection Fraction: The STEP-HFpEF Program.
Journal of the American College of Cardiology2024 Jul 16PMID38913004doi:10.1016/j.jacc.2024.04.038via pubmed nct search
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 (London, England)2024 Apr 27PMID38599221doi:10.1016/S0140-6736(24)00469-0via clinicaltrials gov reference derived + pubmed nct search
Effects of Semaglutide on Symptoms, Function, and Quality of Life in Patients With Heart Failure With Preserved Ejection Fraction and Obesity: A Prespecified Analysis of the STEP-HFpEF Trial.
Circulation2024 Jan 16PMID37952180doi:10.1161/CIRCULATIONAHA.123.067505via clinicaltrials gov reference derived + pubmed nct search
Semaglutide in Patients With Obesity and Heart Failure Across Mildly Reduced or Preserved Ejection Fraction.
Journal of the American College of Cardiology2023 Nov 28PMID37993201doi:10.1016/j.jacc.2023.09.811via clinicaltrials gov reference derived + pubmed nct search
Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity.
The New England journal of medicine2023 Sep 21PMID37622681doi:10.1056/NEJMoa2306963via CT.gov reference + pubmed nct search
Semaglutide in HFpEF across obesity class and by body weight reduction: a prespecified analysis of the STEP-HFpEF trial.
Nature medicine2023 Sep (month)PMID37635157doi:10.1038/s41591-023-02526-xvia CT.gov background + pubmed nct search
Design and Baseline Characteristics of STEP-HFpEF Program Evaluating Semaglutide in Patients With Obesity HFpEF Phenotype.
JACC. Heart failure2023 Aug (month)PMID37294245doi:10.1016/j.jchf.2023.05.010via pubmed nct search

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 1, 2026

Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 1, 2026 snapshot.