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

NCT07738276 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: IRCT20200209046427N3
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Heart Failure and Reduced Ejection Fraction; Obesity & Overweight; Tirzepatide

Keywords

Tirzepatide; GLP-1/GIP receptor agonist; Heart failure with reduced ejection fraction; Obesity; 6-minute walk test; Weight loss; Functional capacity; Randomized controlled trial

Outcome Measures

Primary Outcomes (1)

• Change in 6-Minute Walk Distance

  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 Outcomes (25)

• NYHA Functional Class

  Baseline and 6 months after intervention start

• Glycated Hemoglobin (HbA1c)

  Baseline, end of month 2, end of month 4, and end of month 6

• Fasting Blood Glucose

  Baseline, end of month 2, end of month 4, and end of month 6

• Body Mass Index (BMI)

  Baseline and 6 months after intervention start

• Quality of Life (QoL)

  Baseline and 6 months after intervention start

Other Outcomes (1)

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

  Baseline and 6 months after intervention start

Study Arms (2)

Tirzepatide

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Tirzepatide DRUG

dual GLP-1/GIP receptor agonist administered subcutaneously; brief dosing summary

Also known as: Spartina

Tirzepatide

Placebo DRUG

Matching placebo pen containing all inactive ingredients except tirzepatide

Also known as: Spartina

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Shahid Beheshti University of Medical Sciences: lead

Related Publications (12)

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• Borlaug BA, Zile MR, Kramer CM, Baum SJ, Hurt K, Litwin SE, Murakami M, Ou Y, Upadhyay N, Packer M. 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. Nat Med. 2025 Feb;31(2):544-551. doi: 10.1038/s41591-024-03374-z. Epub 2024 Nov 17.

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MeSH Terms

Conditions

Heart Failure, Systolic; Obesity; Overweight; Weight Loss

Interventions

Tirzepatide

Condition Hierarchy (Ancestors)

Heart Failure; Heart Diseases; Cardiovascular Diseases; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Body Weight Changes

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide

Central Study Contacts

Shadi Shafaghi, MD-MPH-PhD

CONTACT

989125901135; shafaghishadi@yahoo.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The Data Safety Monitoring Committee is also blinded to group allocation throughout the study. In cases of safety-related emergencies, participants will be discontinued from the study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Assistant Professor of Biotechnology.

Model Details: Participants are randomly assigned in a 1:1 ratio to either the tirzepatide group or the placebo group, using permuted block randomization (block size of 4). Both groups continue standard heart failure therapy alongside the study drug or placebo for 6 months.

Study Record Dates

• First Submitted: July 27, 2026
• First Posted: July 31, 2026
• Study Start: July 18, 2026
• Primary Completion (Estimated): June 11, 2027
• Study Completion (Estimated): December 22, 2027
• Last Updated: July 31, 2026

Record last verified: 2026-07