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 (DUAL-HFrEF)

July 30, 2026 updated by: Shadi Shafaghi, Shahid Beheshti University of Medical Sciences

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

The goal of this clinical trial is to learn if tirzepatide works to improve physical function in adults with heart failure and obesity. It will also learn about the safety of tirzepatide. The main questions it aims to answer are:

Does tirzepatide improve how far participants can walk in 6 minutes? Does tirzepatide improve heart failure symptoms and quality of life? What side effects do participants have when taking tirzepatide?

Researchers will compare tirzepatide to a placebo (a look-alike substance that contains no drug) to see if tirzepatide improves physical function in people with heart failure and obesity.

Participants will:

Get a weekly injection of tirzepatide or a placebo under the skin for 6 months Start at a low dose, which may be raised slowly based on how well they tolerate it Keep taking their usual heart failure medicines Visit the clinic for checkups, blood tests, heart ultrasounds, and a 6-minute walk test Answer questions about their quality of life and heart failure symptoms

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a phase 3, randomized, double-blind (participant, care provider, investigator, and outcomes assessor blinded), placebo-controlled, parallel- group clinical trial evaluating the efficacy and safety of tirzepatide, a dual glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist, in participants with heart failure with reduced ejection fraction (HFrEF) and obesity.

Eligible participants are adults aged 18 years or older with HFrEF (left ventricular ejection fraction ≤40% on echocardiography within the prior 3 months), a body mass index ≥27 kg/m² with at least one obesity-related comorbidity (hypertension, diabetes, or dyslipidemia), and stable guideline-directed heart failure therapy for at least 4 weeks prior to enrollment. Key exclusion criteria include recent acute heart failure decompensation or hospitalization, uncontrolled blood pressure, advanced kidney disease (eGFR <30 mL/min/1.73m²), significant hepatic impairment, active pancreatitis, personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2, and pregnancy or breastfeeding.

A total of 60 participants will be randomized 1:1 using a computer-generated block randomization schedule (block size of 4) to receive either tirzepatide or matching placebo, both administered as weekly subcutaneous injections. Study drug is initiated at 2.5 mg once weekly and titrated every 4 weeks, as tolerated, up to a maximum of 10 mg once weekly, continuing through month 6. The placebo pen is identical in appearance, packaging, and dosing schedule to maintain blinding.

The primary outcome is change in 6-minute walk distance from baseline to 6 months. Secondary outcomes include change in New York Heart Association functional class, Kansas City Cardiomyopathy Questionnaire quality-of-life score, body mass index, ejection fraction, pulmonary artery pressure, and metabolic parameters (fasting glucose, glycated hemoglobin, lipid panel), measured at baseline and at months 2, 4, and 6. Safety outcomes include gastrointestinal adverse events, injection-site reactions, hypoglycemia, pancreatitis, gallbladder events, and changes in liver enzymes, amylase, and lipase. An exploratory outcome evaluates shared molecular and genetic pathways linking obesity and HFrEF using peripheral blood RNA analysis via quantitative PCR or next-generation sequencing.

The study is being conducted at seven sites in Tehran, Iran, including Masih Daneshvari Hospital, Shahid Rajaei Cardiovascular Medical and Research Center, Rasoul Akram Hospital, Tehran Heart Center, Firoozgar Hospital, Ayatollah Taleghani Hospital, and Imam Khomeini Hospital Complex.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
60

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Tirzepatide
Participants receive tirzepatide via prefilled subcutaneous injection pen once weekly, in addition to standard heart failure therapy. Starting dose is 2.5 mg once weekly for 4 weeks, titrated based on tolerability every 4 weeks up to a maximum of 10 mg once weekly, continued through month 6.
Drug: Tirzepatide
dual GLP-1/GIP receptor agonist administered subcutaneously; brief dosing summary
Other Names:
  • Spartina
Placebo Comparator: Placebo
Participants receive matching placebo via identical prefilled subcutaneous injection pen once weekly, in addition to standard heart failure therapy, with the same dosing schedule and titration pattern as the tirzepatide group, continued through month 6.
Drug: Placebo
Matching placebo pen containing all inactive ingredients except tirzepatide
Other Names:
  • Spartina

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in 6-Minute Walk Distance
Time Frame: Baseline and 6 months after intervention start
The 6-minute walk test will be performed according to the American Thoracic Society standard guidelines in a straight 30-meter corridor. Participants will be asked to walk as far as possible in 6 minutes at their own pace, with rest breaks permitted if needed. Total distance walked will be recorded in meters. This is a standardized, validated, and reproducible tool for assessing functional capacity and exercise tolerance in patients with heart failure.
Baseline and 6 months after intervention start

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
NYHA Functional Class
Time Frame: Baseline and 6 months after intervention start
Heart failure severity classified according to the New York Heart Association (NYHA) functional classification system.
Baseline and 6 months after intervention start
Glycated Hemoglobin (HbA1c)
Time Frame: Baseline, end of month 2, end of month 4, and end of month 6
Measured using standard biochemical assay kit.
Baseline, end of month 2, end of month 4, and end of month 6
Fasting Blood Glucose
Time Frame: Baseline, end of month 2, end of month 4, and end of month 6
Venous blood sample collected after at least 8 hours of fasting; fasting glucose measured using standard enzymatic glucose oxidase laboratory kit.
Baseline, end of month 2, end of month 4, and end of month 6
Body Mass Index (BMI)
Time Frame: Baseline and 6 months after intervention start
Calculated as weight in kilograms divided by height in meters squared, using standardized stadiometer and scale.
Baseline and 6 months after intervention start
Quality of Life (QoL)
Time Frame: Baseline and 6 months after intervention start
Assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ) score.
Baseline and 6 months after intervention start
Systolic Blood Pressure
Time Frame: Baseline, end of month 2, end of month 4, and end of month 6
Measured using a calibrated automatic blood pressure device after at least 5 minutes of rest in a seated position.
Baseline, end of month 2, end of month 4, and end of month 6
Serum Amylase
Time Frame: Baseline, end of month 2, end of month 4, and end of month 6
Venous blood sample; serum amylase measured using standard colorimetric enzymatic laboratory kit.
Baseline, end of month 2, end of month 4, and end of month 6
Alanine Aminotransferase (ALT)
Time Frame: Baseline, end of month 2, end of month 4, and end of month 6
Venous blood sample; serum ALT measured using standard enzymatic spectrophotometric laboratory kit.
Baseline, end of month 2, end of month 4, and end of month 6
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
Measured using human NT-proBNP ELISA kit.
Baseline, end of month 2, end of month 4, and end of month 6
Total Cholesterol
Time Frame: Baseline, end of month 2, end of month 4, and end of month 6
Venous blood sample collected after at least 8 hours of fasting; total cholesterol measured using standard colorimetric enzymatic laboratory kit.
Baseline, end of month 2, end of month 4, and end of month 6
Ejection Fraction
Time Frame: Baseline, end of month 2, end of month 4, and end of month 6
Assessed by echocardiography.
Baseline, end of month 2, end of month 4, and end of month 6
Number of Participants With Gallbladder Problems
Time Frame: Baseline, end of month 2, end of month 4, and end of month 6
Gallbladder problems (gallstones or cholecystitis) confirmed by abdominal ultrasound.
Baseline, end of month 2, end of month 4, and end of month 6
Number of Participants With Hypoglycemia
Time Frame: Baseline, end of month 2, end of month 4, and end of month 6
Hypoglycemia, defined as blood glucose below 70 mg/dL, measured using standard enzymatic glucose oxidase laboratory kit.
Baseline, end of month 2, end of month 4, and end of month 6
Number of Participants With Injection Site Reactions
Time Frame: Baseline, end of month 2, end of month 4, and end of month 6
Injection site reactions (including redness, swelling, itching, or pain at the injection site) assessed by physical examination.
Baseline, end of month 2, end of month 4, and end of month 6
Number of Participants With Gastrointestinal Adverse Events
Time Frame: Baseline, end of month 2, end of month 4, and end of month 6
Gastrointestinal adverse events (including nausea, vomiting, diarrhea, constipation, or abdominal pain) graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, and assessed through participant interview and monitoring form.
Baseline, end of month 2, end of month 4, and end of month 6
Number of Participants With Pancreatitis
Time Frame: Baseline, end of month 2, end of month 4, and end of month 6
Pancreatitis diagnosed according to the revised Atlanta classification criteria, requiring at least two of the following: characteristic abdominal pain, serum amylase or lipase greater than three times the upper limit of normal, or characteristic findings on abdominal imaging.
Baseline, end of month 2, end of month 4, and end of month 6
Number of Participants With Tachycardia
Time Frame: Baseline, end of month 2, end of month 4, and end of month 6
Tachycardia, defined as a resting heart rate greater than 100 beats per minute measured by pulse oximetry or ECG monitoring at scheduled study visits.
Baseline, end of month 2, end of month 4, and end of month 6
Diastolic Blood Pressure
Time Frame: Baseline, end of month 2, end of month 4, and end of month 6
Measured using a calibrated automatic blood pressure device after at least 5 minutes of rest in a seated position.
Baseline, end of month 2, end of month 4, and end of month 6
Serum Lipase
Time Frame: Baseline, end of month 2, end of month 4, and end of month 6
Venous blood sample; serum lipase measured using standard colorimetric enzymatic laboratory kit.
Baseline, end of month 2, end of month 4, and end of month 6
Aspartate Aminotransferase (AST)
Time Frame: Baseline, end of month 2, end of month 4, and end of month 6
Venous blood sample; serum AST measured using standard enzymatic spectrophotometric laboratory kit.
Baseline, end of month 2, end of month 4, and end of month 6
Alkaline Phosphatase
Time Frame: Baseline, end of month 2, end of month 4, and end of month 6
Venous blood sample; serum alkaline phosphatase measured using standard enzymatic spectrophotometric laboratory kit.
Baseline, end of month 2, end of month 4, and end of month 6
Low-Density Lipoprotein (LDL)
Time Frame: Baseline, end of month 2, end of month 4, and end of month 6
Venous blood sample collected after at least 8 hours of fasting; serum LDL measured using standard colorimetric enzymatic laboratory kit.
Baseline, end of month 2, end of month 4, and end of month 6
High-Density Lipoprotein (HDL)
Time Frame: Baseline, end of month 2, end of month 4, and end of month 6
Venous blood sample collected after at least 8 hours of fasting; serum HDL measured using standard colorimetric enzymatic laboratory kit.
Baseline, end of month 2, end of month 4, and end of month 6
Triglycerides
Time Frame: Baseline, end of month 2, end of month 4, and end of month 6
Venous blood sample collected after at least 8 hours of fasting; serum triglycerides measured using standard colorimetric enzymatic laboratory kit at the central laboratory.
Baseline, end of month 2, end of month 4, and end of month 6
Pulmonary Artery Pressure
Time Frame: Baseline, end of month 2, end of month 4, and end of month 6
Assessed by echocardiography.
Baseline, end of month 2, end of month 4, and end of month 6

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in Gene Expression of Obesity- and Heart Failure-Related Pathways
Time Frame: Baseline and 6 months after intervention start
Venous blood sampling before the intervention and at the end of the study, extraction of ribonucleic acid from peripheral blood samples, and assessment of changes in the expression of genes involved in the shared molecular pathways of obesity and Heart Failure with Reduced Ejection Fraction using quantitative real-time polymerase chain reaction (PCR).
Baseline and 6 months after intervention start

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Shahid Beheshti University of Medical Sciences

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Cinnagen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
July 18, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 11, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 22, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 27, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 30, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 31, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 3, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 30, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRCT20200209046427N3

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

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