Tirzepatide for Heart Failure and Obesity

(SUMMIT Trial)

Recruiting at 245 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

731 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Tirzepatide for heart failure and obesity?

Tirzepatide, a drug that helps control blood sugar and reduce weight, has shown effectiveness in managing type 2 diabetes and obesity. It has been found to significantly reduce body weight and improve heart-related health factors, which may be beneficial for heart failure and obesity. ^{1 2 3 4 5}

Is tirzepatide generally safe for humans?

Tirzepatide has been studied for type 2 diabetes and shows similar side effects to other treatments, mainly nausea, vomiting, diarrhea, and constipation, especially at higher doses. It has been found to be safe for the heart, with no increased risk of major cardiovascular events. ^{1 2 3 6 7}

How is the drug Tirzepatide unique for treating heart failure and obesity?

Tirzepatide is unique because it acts as a dual agonist, targeting both the GIP and GLP-1 receptors, which helps control blood sugar, reduce body weight, and potentially offer cardiovascular benefits. This dual action, not commonly found in other treatments, makes it a novel option for managing heart failure and obesity. ^{1 3 8 9 10}

What is the purpose of this trial?

This trial is testing a medication called Tirzepatide to see if it can help people who have a certain type of heart failure and are also obese. The medication aims to control blood sugar and reduce weight, which may improve their heart condition. Tirzepatide is developed by Eli Lilly and is under investigation for chronic weight management and other conditions.

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

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: Tirzepatide Experimental Treatment 1 Intervention

Tirzepatide administered subcutaneously (SC)

Group II: Placebo Placebo Group 1 Intervention

Placebo administered SC

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

Findings from Research

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 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]

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, 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, 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 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 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Impact of a dual glucose-dependent insulinotropic peptide/glucagon-like peptide-1 receptor agonist tirzepatide on heart rate among patients with type 2 diabetes: A systematic review and pairwise and network meta-analysis. [2023]

2. England 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. [2022]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Tirzepatide: First Approval. [2022]

4. England 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. [2023]

5. Korea (South) pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Tirzepatide in Type 2 Diabetes and Obesity Management. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Tirzepatide: Clinical review of the "twincretin" injectable. [2023]

7. England 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. [2022]

8. Korea (South) pubmed.ncbi.nlm.nih.gov

The Cardiovascular Effect of Tirzepatide: A Glucagon-Like Peptide-1 and Glucose-Dependent Insulinotropic Polypeptide Dual Agonist. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Tirzepatide: A Systematic Update. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Weight loss efficiency and safety of tirzepatide: A Systematic review. [2023]