Tirzepatide for Heart Failure and Obesity

(SUMMIT Trial)

No longer recruiting at 261 trial locations

Overseen By Harvey Serota, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Eli Lilly and Company

Disqualifiers: Cardiomyopathy, Severe valvular disease, Uncontrolled diabetes, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Tirzepatide to determine its effectiveness for people with heart failure and obesity. The researchers aim to assess whether it improves heart function and is safe. Participants will receive either the treatment or a placebo (a harmless pill that resembles the real medicine but has no effect) to compare results. Ideal candidates for this trial are individuals with stable heart failure and obesity, a Body Mass Index (BMI) of 30 or higher, and no recent major heart events. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial requires that you have been on a stable dose of your heart failure medications for at least 4 weeks before screening, so you should not stop taking them.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that tirzepatide is generally safe. Studies have found that patients taking tirzepatide had a lower risk of dying from heart-related issues or experiencing worsening heart failure compared to those taking a placebo. Additionally, tirzepatide is linked to better heart health outcomes, resulting in fewer deaths and fewer major heart or kidney problems for those on the drug.

While researchers continue to study tirzepatide for heart failure and obesity, the FDA has already approved it for treating type 2 diabetes. This approval provides some confidence in its safety. However, all medications can have side effects, and individuals may react differently. It is important to consult a doctor to discuss personal risks and benefits before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Tirzepatide is unique because it tackles both heart failure and obesity by mimicking two hormones that regulate blood sugar and appetite, which is different from standard treatments that typically focus on one condition at a time. Unlike other medications that may require daily dosing, tirzepatide is administered just once a week, making it more convenient for patients. Researchers are excited about tirzepatide because it not only addresses the symptoms but also targets the underlying metabolic processes, offering a potentially more comprehensive approach to treatment.

What evidence suggests that Tirzepatide might be an effective treatment for heart failure and obesity?

Studies have shown that tirzepatide, one of the treatments tested in this trial, can help manage conditions like obesity and a type of heart failure known as HFpEF. Research indicates that tirzepatide, a medication that mimics hormones in the body to control blood sugar and weight, may improve heart function and lower the risk of heart failure. Additional findings suggest that patients using tirzepatide experienced significant weight loss, which is important because obesity is a major risk factor for heart failure. Overall, early evidence is promising, showing that tirzepatide could potentially improve heart health and reduce risks related to obesity. Participants in this trial will receive either tirzepatide or a placebo to evaluate these effects. ^{1 3 4 6 7}

Who Is on the Research Team?

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Principal Investigator

Eli Lilly and Company

Are You a Good Fit for This Trial?

This trial is for adults with heart failure where the heart pumps well (preserved ejection fraction) and who are obese. They must be on stable heart medications, have certain levels of NT-proBNP depending on atrial fibrillation status, experience specific structural heart changes or pressure issues, and have a limited ability to walk distances. Excluded are those with recent major cardiovascular events, acute decompensated heart failure, severe diabetes or kidney disease, other serious health conditions affecting function.

Inclusion Criteria

Your body mass index (BMI) is 30 or higher.

I can walk between 100 to 425 meters without stopping.

Your overall health score is less than or equal to 80.

Exclusion Criteria

I had a sudden worsening of my heart failure within the last month.

I have a serious heart condition related to amyloidosis or valve disease.

My HbA1c level is 9.5% or higher, or my diabetes is not under control.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Tirzepatide or placebo administered subcutaneously

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension

Participants may continue to be monitored until study completion

Up to 120 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Tirzepatide

Trial Overview The study tests Tirzepatide's effectiveness and safety in people with obesity-related preserved ejection fraction heart failure against a placebo. Participants will either receive Tirzepatide or an inactive substance without knowing which one they're getting to compare outcomes fairly.

How Is the Trial Designed?

Group I: Tirzepatide Experimental Treatment 1 Intervention

Participants received a starting dose of 2.5 milligrams (mg) tirzepatide administered subcutaneously (SC) once weekly (QW) and escalated by 2.5 mg every 4 weeks to a maximum of 15 mg QW or maximum tolerated dose (MTD) tolerated by the participant (5 mg QW or 10 mg QW).

Group II: Placebo Placebo Group 1 Intervention

Participants received placebo administered SC QW.

Tirzepatide is already approved in United States, European Union, Canada, United Kingdom for the following indications:

Approved in United States as Mounjaro for:

• Type 2 diabetes

Approved in European Union as Mounjaro for:

• Type 2 diabetes

Approved in Canada as Mounjaro for:

• Type 2 diabetes

Approved in United States as Zepbound for:

• Weight loss
• Moderate to severe obstructive sleep apnea

Approved in United Kingdom as Zepbound for:

• Weight loss

Who Is Running the Clinical Trial?

Eli Lilly and Company

Lead Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Published Research Related to This Trial

Tirzepatide is a new diabetes treatment that effectively controls blood glucose levels by activating both GIP and GLP-1 receptors, which help stimulate insulin secretion and have additional metabolic benefits.

In clinical trials, Tirzepatide not only improved glycemic control but also showed positive effects on blood pressure and lipid levels, leading to its FDA approval for use as a standalone or combination therapy in diabetes management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide: A Systematic Update. Forzano, I., Varzideh, F., Avvisato, R., et al.[2022]

In a study involving 2002 adults with type 2 diabetes and high cardiovascular risk, tirzepatide significantly reduced HbA1c levels more than insulin glargine after 52 weeks, with reductions of -2.43% and -2.58% for tirzepatide 10 mg and 15 mg, respectively, compared to -1.44% for glargine.

Tirzepatide was associated with a lower incidence of hypoglycemia (6-9%) compared to glargine (19%), and it did not increase cardiovascular risk, showing it is a safe and effective option for managing diabetes in high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial. Del Prato, S., Kahn, SE., Pavo, I., et al.[2022]

Tirzepatide, approved in 2022, is a novel treatment for type 2 diabetes that acts on both GLP-1 and GIP pathways, showing significant efficacy in lowering blood sugar levels and promoting weight loss in various patient groups.

Clinical trials, including the SURPASS and SURMOUNT studies, indicate that tirzepatide has a safety profile similar to traditional GLP-1 receptor agonists, with common gastrointestinal side effects, making it a promising option for patients needing better glycemic and weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide: Clinical review of the "twincretin" injectable. Krauss, Z., Hintz, A., Fisk, R.[2023]

Tirzepatide, the first dual GIP/GLP-1 receptor co-agonist approved for type 2 diabetes, significantly reduces HbA1c levels (by 1.24 to 2.58%) and body weight (by 5.4-11.7 kg) in clinical trials involving type 2 diabetic patients, outperforming the selective GLP-1 RA semaglutide.

The safety profile of tirzepatide is similar to that of other GLP-1 receptor agonists, with common side effects including nausea and diarrhea, and it shows potential cardiovascular safety, as no significant increase in major adverse cardiovascular events was observed during the trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide, a dual GIP/GLP-1 receptor co-agonist for the treatment of type 2 diabetes with unmatched effectiveness regrading glycaemic control and body weight reduction. Nauck, MA., D'Alessio, DA.[2022]

Tirzepatide, a dual GLP-1/GIP receptor co-agonist, has been shown to significantly reduce glycosylated hemoglobin levels (1.87% to 3.02%) and body weight (5.4 to 12.9 kg) in people with type 2 diabetes over treatment periods of up to 104 weeks, demonstrating its efficacy compared to placebo and other diabetes medications.

In individuals without diabetes, tirzepatide also led to substantial weight loss (16.5% to 22.4%) over 72 weeks, indicating its potential for obesity management as well.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Tirzepatide in Type 2 Diabetes and Obesity Management. Sinha, R., Papamargaritis, D., Sargeant, JA., et al.[2023]

Tirzepatide, a dual GLP-1 and GIP receptor agonist, has shown significant reductions in glycated hemoglobin levels and body weight in patients with type 2 diabetes mellitus (T2DM) during phase 3 clinical trials.

In addition to its glucose-lowering and weight loss effects, tirzepatide may also offer cardiovascular benefits, highlighting its potential as a comprehensive treatment for T2DM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Cardiovascular Effect of Tirzepatide: A Glucagon-Like Peptide-1 and Glucose-Dependent Insulinotropic Polypeptide Dual Agonist. Cho, YK., La Lee, Y., Jung, CH.[2023]

Tirzepatide significantly reduces body weight in patients with type 2 diabetes and obesity, with an average weight loss of -9.81 kg compared to placebo, based on a meta-analysis of 10 studies involving 9,873 patients.

While tirzepatide is effective for weight loss, it has a higher incidence of gastrointestinal side effects compared to placebo, although serious adverse events and hypoglycemia are less common, indicating a need for monitoring these reactions during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weight loss efficiency and safety of tirzepatide: A Systematic review. Lin, F., Yu, B., Ling, B., et al.[2023]

In a 72-week phase 3 trial involving 938 adults with obesity and type 2 diabetes, tirzepatide (10 mg and 15 mg) led to significant weight loss, with reductions of -12.8% and -14.7% respectively, compared to only -3.2% with placebo.

The safety profile of tirzepatide was generally favorable, with most adverse events being mild to moderate gastrointestinal issues, and serious adverse events were rare, indicating it is a safe option for weight management in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Garvey, WT., Frias, JP., Jastreboff, AM., et al.[2023]

Tirzepatide is a novel medication that acts on both GIP and GLP-1 receptors, enhancing insulin secretion and reducing glucagon levels, which helps improve glycemic control in adults with type 2 diabetes mellitus (T2DM).

It received its first approval in the USA in May 2022 for T2DM treatment and is currently being studied for additional conditions like obesity, heart failure, and non-alcoholic steatohepatitis, indicating its potential for broader therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide: First Approval. Syed, YY.[2022]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S1071916425000910

Efficacy of GLP-1 Receptor Agonists in Patients With Heart ... Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity. ... heart failure outcomes in diabetes and chronic kidney disease in the FLOW trial.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39555826/

Tirzepatide for Heart Failure with Preserved Ejection ... Background: Obesity increases the risk of heart failure with preserved ejection fraction. Tirzepatide, a long-acting agonist of glucose- ...

3. nejm.org nejm.org/doi/abs/10.1056/NEJMoa2410027

Tirzepatide for Heart Failure with Preserved Ejection ... Obesity increases the risk of heart failure with preserved ejection fraction. Tirzepatide, a long-acting agonist of glucose-dependent ...

4. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2822209

Clinical Outcomes of Tirzepatide or GLP-1 Receptor ... 53. A study of tirzepatide (LY3298176) in participants with heart failure with preserved ejection fraction (HfpEF) and obesity: the SUMMIT trial ...

5. jacc.org jacc.org/doi/10.1016/j.jacadv.2025.101740

An Observational Study of Cardiovascular Outcomes ... The SUMMIT trial (NCT04847557) will explore the role of tirzepatide in heart failure with preserved ejection fraction and obesity. Tirzepatide's effect on ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12409218/

Tirzepatide and cardiometabolic parameters in obesity Cumulatively, these findings support a potential association between tirzepatide and improved cardiovascular safety, though outcomes trials will ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12166642/

Tirzepatide, a dual GIP/GLP1-receptor co-agonist preserves ... Tirzepatide, a dual GIP/GLP1-receptor co-agonist preserves cardiac function and improves survival in angiotensin II-induced heart failure model in mice.