STEP HFpEF DM

CompletedPhase 3

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

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

Lead sponsor

Novo Nordisk A/S

Asset

Semaglutide

Subcutaneous · GLP-1 agonist

Listed sites

180

Recruiting sites

—

Enrollment

617

actual

Study population

Heart failure, Obesity / overweight, Type 2 diabetes

Key I/E criteria

•BMI ≥30•EF ≥45%

Primary endpoints

•KCCQ clinical summary•Body weight, % change

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 IDNCT04916470

Org study IDEX9536-4773

Secondary ID2020-004170-22

Secondary IDU1111-1257-5069World Health Organization (WHO)

Timeline

Milestones

Study first posted2021-06-07actual

Study start2021-06-15actual

Primary completion2023-10-11actual

Study completion2023-10-11actual

Last update posted2025-11-26actual

Assets

Investigational agents

Semaglutide

Study populations

Who this study enrolls

Heart failureObesity / overweightType 2 diabetes

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% 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.

Endpoints (23)

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

Cardiovascular outcomes

Glycemic / diabetes

Safety / tolerability / PK

Cardiovascular outcomes

1 endpoint

Secondary/protocol endpoint

Hierarchical composite of time to all-cause death

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

All-cause death

time to event, event

SNOMED 419620001

Weight & body composition

5 endpoints

Primary/protocol endpoint

Change in body weight

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

Body weight, % change

percent change from baseline, improvement

Secondary/protocol endpoint

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

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

≥10% weight-loss responders

threshold achievement, improvement

Secondary/protocol endpoint

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

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

≥15% weight-loss responders

threshold achievement, improvement

Secondary/protocol endpoint

Participant achieving 20% weight loss or more (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

Glycemic / diabetes

1 endpoint

Secondary/protocol endpoint

Change in glycated haemoglobin (HbA1c)

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

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Heart failure

13 endpoints

Primary/protocol endpoint

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

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

KCCQ clinical summary

change from baseline, improvement

Secondary/protocol endpoint

Change in 6-minute walking distance

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

6-minute walk distance

change from baseline, improvement

Secondary/protocol endpoint

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)

Heart-failure composite

event count, event

componentsHeart-failure hospitalization, Urgent heart-failure visit

SNOMED 84114007

Secondary/protocol endpoint

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)

Heart-failure composite

time to event, event

componentsHeart-failure hospitalization, Urgent heart-failure visit

SNOMED 84114007

Secondary/protocol endpoint

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)

KCCQ clinical summary

threshold achievement, improvement

Secondary/protocol endpoint

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)

KCCQ clinical summary

threshold achievement, improvement

Secondary/protocol endpoint

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)

KCCQ clinical summary

change from baseline, improvement

Secondary/protocol endpoint

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)

6-minute walk distance

change from baseline, improvement

Secondary/protocol endpoint

Participant improving 5 points or more in KCCQ clinical summary score

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

KCCQ clinical summary

threshold achievement, improvement

Secondary/protocol endpoint

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)

KCCQ clinical summary

threshold achievement, improvement

Secondary/protocol endpoint

Change in KCCQ overall summary score

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

KCCQ total score

change from baseline, improvement

Secondary/protocol endpoint

Participant achieving threshold for clinically meaningful within-subject change in KCCQ-CSS

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

KCCQ clinical summary

threshold achievement, improvement

Secondary/protocol endpoint

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

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

6-minute walk distance

threshold achievement, improvement

Cardiometabolic biomarkers

2 endpoints

Secondary/protocol endpoint

Change in C-Reactive Protein

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

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

Systolic BP, change

change from baseline, improvement

LOINC 8480-6

Safety / tolerability / PK

1 endpoint

Secondary/protocol endpoint

Number of treatment emergent severe or clinically significant hypoglycaemia episodes

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

Severe hypoglycemia

event count, event

Publications (13)

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 clinicaltrials gov reference derived + 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 clinicaltrials gov reference derived + pubmed nct search
Semaglutide in obesity-related heart failure with preserved ejection fraction and type 2 diabetes across baseline HbA(1c) levels (STEP-HFpEF DM): a prespecified analysis of heart failure and metabolic outcomes from a randomised, placebo-controlled trial.
The lancet. Diabetes & endocrinology2025 Mar (month)PMID39848268doi:10.1016/S2213-8587(24)00304-8via clinicaltrials gov reference derived + 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 clinicaltrials gov reference derived + 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 clinicaltrials gov reference derived + 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 clinicaltrials gov reference derived + 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 clinicaltrials gov reference derived + 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 clinicaltrials gov reference derived + 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
Semaglutide in Patients with Obesity-Related Heart Failure and Type 2 Diabetes.
The New England journal of medicine2024 Apr 18PMID38587233doi:10.1056/NEJMoa2313917via clinicaltrials gov reference derived + 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 CT.gov background + 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 tableno registry results posted yet

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.