DUAL-HFrEF

Not yet recruitingPhase 3

Evaluation of the Efficacy and Safety of Tirzepatide, a Dual GLP-1/GIP Agonist, on Functional Capacity in Reduced Ejection Fraction Heart Failure Patients With Obesity

Evaluation of the Efficacy and Safety of Tirzepatide, a Dual GLP-1/GIP Agonist, on Functional Capacity in Reduced Ejection Fraction Heart Failure Patients With Obesity: A Double-Blinded Randomized Controlled Trial

Lead sponsor

Shahid Beheshti University of Medical Sciences

Asset

Tirzepatide

Subcutaneous · GLP-1 / GIP dual

Listed sites

Recruiting sites

Estimated enrollment

Study population

Heart failure, Obesity / overweight

Eligibility highlights

•BMI ≥27•EF ≤40%

Primary endpoint

•6-Minute Walk Distance

Registered trial locations

Locations reported to ClinicalTrials.gov for this trial snapshot. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT07738276

Org study IDIRCT20200209046427N3

Timeline

Milestones

Study start2026-07-18estimated

Study first posted2026-07-31actual

Last update posted2026-08-03actual

Primary completion2027-06-11estimated

Study completion2027-12-22estimated

Assets

Investigational agents

Tirzepatide

Who this study enrolls

Heart failureObesity / overweight

Who can enroll

Minimum age18 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Age 18 years or older

•Heart failure with reduced ejection fraction, defined as left ventricular ejection fraction ≤40% on echocardiography performed within the prior 3 months

•Body mass index ≥27 kg/m², with at least one obesity-related comorbidity (hypertension, diabetes, or dyslipidemia)

•Stable heart failure therapy for at least 4 weeks prior to enrollment, including beta-blockers, renin-angiotensin system inhibitors/angiotensin receptor-neprilysin inhibitors, and sodium-glucose cotransporter-2 inhibitors, if prescribed

•Written informed consent

Exclusion criteria

•Acute heart failure decompensation or cardiac hospitalization within the prior 4 weeks

•Uncontrolled blood pressure (systolic blood pressure <90 mmHg or ≥180 mmHg)

•Advanced renal impairment (estimated glomerular filtration rate <30 mL/min/1.73m²)

•Severe hepatic impairment (liver enzymes elevated to 3 times the upper limit of normal)

•Active pancreatitis

•Personal or first-degree family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2

•Pregnancy or breastfeeding

•Known hypersensitivity to glucagon-like peptide-1 (GLP-1) or glucose-dependent insulinotropic polypeptide (GIP) receptor agonist drugs

•Concurrent use of other weight-loss medications

Endpoints (27)

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

Cardiometabolic biomarkers

Safety / tolerability / PK

Heart failure

Other (unclassified)

Glycemic / diabetes

MASH / liver

Weight & body composition

Patient-reported / QoL

Weight & body composition

1 endpoint

Secondary/protocol endpoint

Body Mass Index (BMI)

Time frame:Baseline and 6 months after intervention start

descriptive

Glycemic / diabetes

2 endpoints

Secondary/protocol endpoint

Glycated Hemoglobin (HbA1c)

Time frame:Baseline, end of month 2, end of month 4, and end of month 6

descriptive

Secondary/protocol endpoint

Fasting Blood Glucose

Time frame:Baseline, end of month 2, end of month 4, and end of month 6

descriptive

MASH / liver

2 endpoints

Secondary/protocol endpoint

Alanine Aminotransferase (ALT)

Time frame:Baseline, end of month 2, end of month 4, and end of month 6

descriptive

Secondary/protocol endpoint

Aspartate Aminotransferase (AST)

Time frame:Baseline, end of month 2, end of month 4, and end of month 6

descriptive

Heart failure

5 endpoints

Primary/protocol endpoint

Change in 6-Minute Walk Distance

Time frame:Baseline and 6 months after intervention start

change from baseline, improvement

Secondary/protocol endpoint

NYHA Functional Class

Time frame:Baseline and 6 months after intervention start

descriptive

Secondary/protocol endpoint

N-terminal Pro B-type Natriuretic Peptide (NT-proBNP)

Time frame:Baseline, end of month 2, end of month 4, and end of month 6

descriptive

Secondary/protocol endpoint

Ejection Fraction

Time frame:Baseline, end of month 2, end of month 4, and end of month 6

descriptive

Other/protocol endpoint

Change in Gene Expression of Obesity- and Heart Failure-Related Pathways

Time frame:Baseline and 6 months after intervention start

change from baseline, improvement

Cardiometabolic biomarkers

6 endpoints

Secondary/protocol endpoint

Systolic Blood Pressure

Time frame:Baseline, end of month 2, end of month 4, and end of month 6

descriptive

Secondary/protocol endpoint

Total Cholesterol

Time frame:Baseline, end of month 2, end of month 4, and end of month 6

descriptive

Secondary/protocol endpoint

Diastolic Blood Pressure

Time frame:Baseline, end of month 2, end of month 4, and end of month 6

descriptive

Secondary/protocol endpoint

Low-Density Lipoprotein (LDL)

Time frame:Baseline, end of month 2, end of month 4, and end of month 6

descriptive

Secondary/protocol endpoint

High-Density Lipoprotein (HDL)

Time frame:Baseline, end of month 2, end of month 4, and end of month 6

descriptive

Secondary/protocol endpoint

Triglycerides

Time frame:Baseline, end of month 2, end of month 4, and end of month 6

descriptive

Patient-reported / QoL

1 endpoint

Secondary/protocol endpoint

Quality of Life (QoL)

Time frame:Baseline and 6 months after intervention start

descriptive

Safety / tolerability / PK

6 endpoints

Secondary/protocol endpoint

Number of Participants With Gallbladder Problems

Time frame:Baseline, end of month 2, end of month 4, and end of month 6

event count, event

Secondary/protocol endpoint

Number of Participants With Hypoglycemia

Time frame:Baseline, end of month 2, end of month 4, and end of month 6

event count, event

Secondary/protocol endpoint

Number of Participants With Injection Site Reactions

Time frame:Baseline, end of month 2, end of month 4, and end of month 6

event count, event

Secondary/protocol endpoint

Number of Participants With Gastrointestinal Adverse Events

Time frame:Baseline, end of month 2, end of month 4, and end of month 6

event count, event

Secondary/protocol endpoint

Number of Participants With Pancreatitis

Time frame:Baseline, end of month 2, end of month 4, and end of month 6

event count, event

Secondary/protocol endpoint

Number of Participants With Tachycardia

Time frame:Baseline, end of month 2, end of month 4, and end of month 6

event count, event

Other (unclassified)

4 endpoints

Secondary/protocol endpoint/low confidence

Serum Amylase

Time frame:Baseline, end of month 2, end of month 4, and end of month 6

descriptive

Secondary/protocol endpoint/low confidence

Serum Lipase

Time frame:Baseline, end of month 2, end of month 4, and end of month 6

descriptive

Secondary/protocol endpoint/low confidence

Alkaline Phosphatase

Time frame:Baseline, end of month 2, end of month 4, and end of month 6

descriptive

Secondary/protocol endpoint/low confidence

Pulmonary Artery Pressure

Time frame:Baseline, end of month 2, end of month 4, and end of month 6

descriptive

Publications (12)

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

Effects of Tirzepatide on the Clinical Trajectory of Patients With Heart Failure, Preserved Ejection Fraction, and Obesity.
Circulation2025 Mar 11PMID39556714doi:10.1161/CIRCULATIONAHA.124.072679via CT.gov background
Effects of tirzepatide on circulatory overload and end-organ damage in heart failure with preserved ejection fraction and obesity: a secondary analysis of the SUMMIT trial.
Nature medicine2025 Feb (month)PMID39551891doi:10.1038/s41591-024-03374-zvia CT.gov background
Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity.
The New England journal of medicine2025 Jan 30PMID39555826doi:10.1056/NEJMoa2410027via CT.gov background
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 CT.gov background
Tirzepatide reduces the predicted risk of atherosclerotic cardiovascular disease and improves cardiometabolic risk factors in adults with obesity or overweight: SURMOUNT-1 post hoc analysis.
Diabetes, obesity & metabolism2024 Jan (month)PMID37932236doi:10.1111/dom.15318via CT.gov background
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 background
Petrie MC, Borlaug BA, Butler J, Davies MJ, Kitzman DW, Shah SJ, Verma S, Jensen TJ, Einfeldt MN, Liisberg K, Perna E, Sharma K, Ezekowitz JA, Fu M, Melenovsky V, Ito H, Lelonek M, Kosiborod MN; STEP-HFpEF Trial Committees and Investigators. Semaglutide and NT-proBNP in Obesity-Related HFpEF: Insights From the STEP-HFpEF Program. J Am Coll Cardiol. 2024 Jul 2;84(1):27-40. doi: 10.1016/j.jacc.2024.04.022. Epub 2024 May 13.
PMID38819334via CT.gov background
Wallner M, Biber ME, Stolfo D, Sinagra G, Benson L, Dahlstrom U, Gudbjornsdottir S, Cosentino F, Mol PGM, Rosano GMC, Butler J, Metra M, Lund LH, Ferrannini G, Savarese G. Glucagon-like peptide-1 receptor agonists use and associations with outcomes in heart failure and type 2 diabetes: data from the Swedish Heart Failure and Swedish National Diabetes Registries. Eur Heart J Cardiovasc Pharmacother. 2024 Jul 16;10(4):296-306. doi: 10.1093/ehjcvp/pvae026.
PMID38632048via CT.gov background
Hinney A, Nguyen TT, Scherag A, Friedel S, Bronner G, Muller TD, Grallert H, Illig T, Wichmann HE, Rief W, Schafer H, Hebebrand J. Genome wide association (GWA) study for early onset extreme obesity supports the role of fat mass and obesity associated gene (FTO) variants. PLoS One. 2007 Dec 26;2(12):e1361. doi: 10.1371/journal.pone.0001361.
PMID18159244via CT.gov background
Mahley RW. Apolipoprotein E: cholesterol transport protein with expanding role in cell biology. Science. 1988 Apr 29;240(4852):622-30. doi: 10.1126/science.3283935.
PMID3283935via CT.gov background
Klarin D, Natarajan P. Clinical utility of polygenic risk scores for coronary artery disease. Nat Rev Cardiol. 2022 May;19(5):291-301. doi: 10.1038/s41569-021-00638-w. Epub 2021 Nov 22.
PMID34811547via CT.gov background
Kathiresan S, Melander O, Guiducci C, Surti A, Burtt NP, Rieder MJ, Cooper GM, Roos C, Voight BF, Havulinna AS, Wahlstrand B, Hedner T, Corella D, Tai ES, Ordovas JM, Berglund G, Vartiainen E, Jousilahti P, Hedblad B, Taskinen MR, Newton-Cheh C, Salomaa V, Peltonen L, Groop L, Altshuler DM, Orho-Melander M. Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans. Nat Genet. 2008 Feb;40(2):189-97. doi: 10.1038/ng.75. Epub 2008 Jan 13.
PMID18193044via CT.gov background

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateNovember 5, 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 November 5, 2026 snapshot.