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DUP-STEP-HFpEF

Completed

Emulation of the STEP-HFpEF DM Heart Failure Trial in Healthcare Claims Data

Lead sponsor

Brigham and Women's Hospital

Asset

Semaglutide

GLP-1 agonist

Listed sites

Recruiting sites

—

Enrollment

58,387

actual

Study population

Heart failure, Obesity / overweight, Type 2 diabetes

Key I/E criteria

•BMI ≥30•EF ≥45%

Primary endpoint

•Expanded / custom MACE composite (All-cause death, Heart-failure hospitalization)

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 IDNCT06914102

Org study ID2018P002966-DUP-STEP-HFpEF

Timeline

Milestones

Study start2025-01-14actual

Study first posted2025-04-06actual

Primary completion2025-06-01actual

Study completion2025-06-01actual

Last update posted2026-01-30actual

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

Sampling methodNon probability sample

Study population text

The study population included individuals aged 18 years or older with heart failure with preserved ejection fraction when following and relaxing the eligibility criteria of the STEP-HFpEF DM trial.

Inclusion criteria

Eligible cohort entry dates:

Optum: Study period between January 1, 2018 to November 30, 2024. Marketscan: Study period between January 1, 2018 to December 31, 2023. Medicare: Study period between January 1, 2018 to December 31, 2020.

FOLLOWING ELIGIBILITY OF THE STEP-HFpEF DM TRIAL

Inclusion Criteria:

•Male or female, age above or equal to 18 years at the time of signing informed consent.

•BMI ≥ 30.0 kg/m2

•NYHA Class II-IV

•LVEF ≥ 45%

•No hospitalizations due to heart failure between screening (V1) and randomization (V2)

•At least one of the following:

•If BMI <35.0: NT-proBNP ≥ 220 pg/mL (for patients with sinus rhythm) or NTproBNP ≥660 pg/mL (for patients with persistent/permanent atrial fibrillation); if BMI ≥ 35.0: NT-proBNP ≥ 125 pg/mL (for patients with sinus rhythm) or NTproBNP ≥ 375 pg/mL (for patients with persistent/permanent atrial fibrillation) at screening (NT-proBNP analyzed by the central laboratory) in combination with at least one of the following (documented by echocardiography within 12 months prior to or at screening):

i.Septal é < 7cm/sec or lateral é < 10 cm/sec or average E/é ≥ 15

ii.PA systolic pressure >35mmHg

iii.Left atrial (LA) enlargement (LA width ≥3.8 cm or LA length ≥ 5.0cm or LA area ≥ 20.0cm2 or LA volume ≥ 55mL or LA volume index ≥29mL/m2)

iv.LV hypertrophy with septal thickness or posterior wall thickness ≥1.2cm

•Hospitalization with a primary diagnosis of decompensated heart failure which required intravenous loop diuretic treatment, within the previous 12 months in combination with at least two of the following (documented by echocardiography within 12 months prior to or at screening):

i.Septal é < 7cm/sec or lateral é < 10cm/sec or average E/é ≥15

ii.PA systolic pressure >35mmHg

iii.LA enlargement (LA width ≥3.8cm or LA length ≥ 5.0cm or LA area ≥20.0cm2 or LA volume ≥ 55mL or LA volume index ≥ 29mL/m2)

iv.LV hypertrophy with septal thickness or posterior wall thickness ≥1.2cm

•Diagnosed with T2D ≥ 90 days prior to the day of screening.

•Subject treated with diet, exercise, and/or antidiabetic treatment* according to local label in stable dosing for at least 30 days prior to screening: o *OAD(s): unchanged drug(s), dose and dosing frequency o *Insulin(s): unchanged regimen (basal, basal + bolus, premix combination) with stable total daily insulin dose as judged by the investigator

Exclusion criteria

•Myocardial infarction, stroke, hospitalization for heart failure, unstable angina pectoris or transient ischemic attack within 30 days prior to the day of screening.

•Systolic blood pressure > 160 mmHg at screening.

•Any other condition judged by the investigator to be the primary cause of dyspnea (such as heart failure due to restrictive cardiomyopathy or infiltrative conditions (e.g. amyloidosis), hypertrophic obstructive cardiomyopathy, primary pulmonary arterial hypertension, chronic obstructive pulmonary disease, right heart failure due to pulmonary disease, complex congenital heart disease, anemia, or more than moderate heart valve disease).

•Bariatric surgery prior to screening or planned bariatric surgery within the trial time course.

•History of type 1 diabetes (history of gestational diabetes is allowed).

•Treatment with any GLP-1 receptor agonist within 90 days prior to the day of screening.

•Uncontrolled and potentially unstable diabetic retinopathy or maculopathy.

•Recurrent severe hypoglycemic episodes within the last year as judged by the investigator.

•Treatment with continuous subcutaneous insulin infusion

•Personal or first-degree relative(s) history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma.

•Presence of acute pancreatitis within the last 180 days prior to screening.

•History or presence of chronic pancreatitis.

•End-stage renal disease or chronic or intermittent hemodialysis or peritoneal dialysis.

•Presence or history of malignant neoplasm within 5 years prior to the day of screening. Basal and squamous cell cancer and any carcinoma in-situ are allowed.

•Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using a highly effective contraceptive method.

•Any disorder, including severe psychiatric disorder, suicidal behavior within 90 days before screening, and suspected drug abuse, which in the investigator´s opinion might jeopardize subject´s safety or compliance with the protocol.

RELAXING ELIGIBILITY OF THE STEP-HFpEF DM TRIAL

Inclusion Criteria:

•Men or women ≥ 18 years old

•History of type 2 diabetes mellitus

•BMI ≥ 27.0 kg/m2

•Heart failure

•Preserved ejection fraction

Exclusion Criteria:

•Prior treatment with any GLP-1-RA

•History of type 1 diabetes mellitus

•End-stage renal disease or chronic or intermittent hemodialysis or peritoneal dialysis

•History of bariatric surgery

•History of nursing home admission

•Pregnant female or breast-feeding

•Uncontrolled and potentially unstable diabetic retinopathy or maculopathy

•Treatment with continuous subcutaneous insulin infusion

•Multiple endocrine neoplasia type 2 or medullary thyroid carcinoma

•Have a history of an active or untreated malignancy or are in remission from a clinically significant malignancy (other than basal- or squamous-cell skin cancer, in situ carcinoma of the cervix, or in situ prostate cancer) for less than 5 years

Endpoints (11)

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

Safety / tolerability / PK

Cardiovascular outcomes

Other clinical outcomes

Cardiovascular outcomes

2 endpoints

Primary/protocol endpoint

Composite of all-cause mortality or heart failure hospitalization

Time frame:Through study completion (1 day after cohort entry date until the first of outcome or censoring)

Expanded / custom MACE composite

time to event, event

componentsAll-cause death, Heart-failure hospitalization

Secondary/protocol endpoint

All-cause mortality

Time frame:Through study completion (1 day after cohort entry date until the first of outcome or censoring)

All-cause death

time to event, event

SNOMED 419620001

Heart failure

4 endpoints

Secondary/protocol endpoint

Composite of all-cause mortality or a worsening heart failure event (exacerbated symptoms of heart failure resulting in hospitalization, intravenous diuretic therapy in an urgent care setting), and its respective individual end points.

Time frame:Through study completion (1 day after cohort entry date until the first of outcome or censoring)

Heart-failure composite

time to event, event

componentsAll-cause death, Heart-failure hospitalization, Urgent heart-failure visit

Secondary/protocol endpoint

Worsening heart failure event (exacerbated symptoms of heart failure resulting in hospitalization or intravenous diuretic therapy in an urgent care setting)

Time frame:Through study completion (1 day after cohort entry date until the first of outcome or censoring)

Heart-failure composite

time to event, event

componentsHeart-failure hospitalization, Urgent heart-failure visit

SNOMED 84114007

Secondary/protocol endpoint

Intravenous diuretic therapy in an urgent care setting

Time frame:Through study completion (1 day after cohort entry date until the first of outcome or censoring)

Urgent heart-failure visit

time to event, event

Secondary/protocol endpoint

Hospitalization for heart failure

Time frame:Through study completion (1 day after cohort entry date until the first of outcome or censoring)

Heart-failure hospitalization

time to event, event

SNOMED 84114007

Safety / tolerability / PK

3 endpoints

Secondary/protocol endpoint

Urinary tract infection

Time frame:Through study completion (1 day after cohort entry date until the first of outcome or censoring)

time to event, event

Secondary/protocol endpoint

Serious bacterial infection

Time frame:Through study completion (1 day after cohort entry date until the first of outcome or censoring)

time to event, event

Secondary/protocol endpoint

Gastrointestinal adverse events

Time frame:Through study completion (1 day after cohort entry date until the first of outcome or censoring)

descriptive, event

Other clinical outcomes

2 endpoints

Other/protocol endpoint

Hernia

Time frame:Through study completion (1 day after cohort entry date until the first of outcome or censoring)

time to event, event

Other/protocol endpoint/low confidence

Lumbar radiculopathy

Time frame:Through study completion (1 day after cohort entry date until the first of outcome or censoring)

time to event, event

Publications (1)

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 Tirzepatide in Patients With Heart Failure With Preserved Ejection Fraction.
JAMA2025 Oct 14PMID40886075doi:10.1001/jama.2025.14092via clinicaltrials gov reference derived + 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.