Semaglutide + Lifestyle Counseling for Heart Failure

Overseen By Alyssa C. Ploof

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must be taking: Diuretics

Must not be taking: GLP-1 agonists

Disqualifiers: Myocardial infarction, Stroke, Diabetes, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

81 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this research is to find out if an aggressive intervention to lose weight, will improve symptoms in patients with obesity-related cardiomyopathy, which is also known as the obese phenotype of heart failure with preserved ejection fraction (HFpEF).

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are currently using a GLP-1 receptor agonist, you must stop at least 90 days before the screening.

What data supports the effectiveness of the drug semaglutide for heart failure?

Research shows that semaglutide, a medication used for type 2 diabetes, can reduce major cardiovascular events and improve symptoms in patients with heart failure and obesity, suggesting potential benefits for heart failure management. ^{1 2 3 4 5}

Is semaglutide safe for humans?

Semaglutide has been studied for safety in people with type 2 diabetes and heart failure, showing a safety profile similar to other treatments in its class. It was found to be safe for the heart, with no more risk than a placebo in high-risk patients. ^{1 2 3 6 7}

How is the drug semaglutide unique for heart failure treatment?

Semaglutide is unique for heart failure treatment because it is a glucagon-like peptide-1 receptor agonist, originally used for type 2 diabetes, that helps manage blood sugar and reduce cardiovascular events, and it is now being explored for its potential benefits in heart failure when combined with lifestyle counseling. ^{3 7 8 9 10}

Research Team

Barry Borlaug, MD

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for adults with obesity-related heart issues (HFpEF) who have a BMI of 30 or higher, experience certain types of heart failure symptoms, and haven't been hospitalized for heart failure in the last month. People can't join if they've had bariatric surgery, used GLP-1 receptor agonists recently, have specific health risks like pancreatitis or severe psychiatric disorders, are pregnant or not using effective contraception, plan major surgery that affects walking ability during the trial period.

Inclusion Criteria

I have moderate to severe heart condition symptoms.

LVEF ≥ 50% within the preceding year

BMI ≥ 30.0 kg/m2

Exclusion Criteria

Systolic blood pressure > 160 mmHg at screening

General health and safety exclusions such as history of neoplasms, hypersensitivity, recent participation in clinical trials, pregnancy, major surgery, and psychiatric disorders or drug abuse

I have had recent heart problems or plan to undergo a procedure to improve blood flow.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Semaglutide or placebo once weekly in addition to counselling on healthy lifestyle intervention

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Counselling on healthy lifestyle intervention
• Placebo
• Semaglutide

Trial Overview The study tests whether an aggressive weight loss intervention combined with Semaglutide improves symptoms in patients with HFpEF compared to a placebo group. Participants will also receive counseling on healthy lifestyle changes as part of the treatment process.

Participant Groups

Group I: Semaglutide Treatment Active Control 2 Interventions

Subjects will receive Semaglutide once weekly in addition to counselling on healthy lifestyle intervention

Group II: Placebo Treatment Placebo Group 2 Interventions

Subjects will receive matching placebo once weekly in addition to counselling on healthy lifestyle intervention

Semaglutide is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in United States as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in Canada as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in Japan as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in United States as Wegovy for:

• Obesity

Approved in United States as Rybelsus for:

• Type 2 diabetes

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Findings from Research

In the combined analysis of the SUSTAIN and PIONEER trials, semaglutide significantly reduced the risk of major adverse cardiovascular events (MACE) by 24% compared to placebo, primarily due to a reduction in nonfatal strokes.

However, semaglutide did not show a beneficial effect on hospitalization for heart failure, particularly in patients with a history of heart failure, indicating that its cardiovascular benefits may not extend to all high-risk groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide (SUSTAIN and PIONEER) reduces cardiovascular events in type 2 diabetes across varying cardiovascular risk. Husain, M., Bain, SC., Jeppesen, OK., et al.[2021]

The PIONEER 6 trial is assessing the cardiovascular safety of oral semaglutide in 3183 patients with type 2 diabetes at high risk for cardiovascular events, aiming to determine if it poses any additional cardiovascular risk compared to a placebo.

The study will evaluate the time to first occurrence of serious cardiovascular events, such as CV death or non-fatal heart attacks and strokes, providing important data on the safety of this new oral medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular safety of oral semaglutide in patients with type 2 diabetes: Rationale, design and patient baseline characteristics for the PIONEER 6 trial. Bain, SC., Mosenzon, O., Arechavaleta, R., et al.[2021]

In a study of 136 obese patients with type 2 diabetes and heart failure, once-weekly semaglutide significantly improved heart failure symptoms and functional status, as evidenced by a notable increase in Kansas City Cardiomyopathy Questionnaire scores and a reduction in patients classified as New York Heart Association functional class III.

Semaglutide was found to be safe and well-tolerated, leading to significant reductions in glycated hemoglobin and body weight, while also decreasing hospitalizations related to heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Semaglutide for the Management of Obese Patients With Type 2 Diabetes and Chronic Heart Failure in Real-World Clinical Practice. Pérez-Belmonte, LM., Sanz-Cánovas, J., García de Lucas, MD., et al.[2022]

The STEP-HFpEF trial investigated the effects of semaglutide in patients with heart failure with preserved ejection fraction (HFpEF) and obesity, demonstrating significant improvements in heart failure symptoms and weight loss among participants.

This study involved a substantial number of patients, providing strong evidence that semaglutide can be an effective treatment option for managing both heart failure and obesity, potentially enhancing patient quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In patients with HFpEF and obesity, semaglutide increased weight loss and reduced symptoms and physical limitations at 52 wk. Ali, HJ., Deswal, A.[2023]

In a pooled analysis of 6,480 participants from the SUSTAIN 6 and PIONEER 6 trials, adding semaglutide to standard care significantly reduced the risk of major adverse cardiovascular events (MACE) with a hazard ratio of 0.76, indicating a 24% reduction in risk.

Patients with type 2 diabetes who added semaglutide gained an average of 1.7 life-years free of cardiovascular disease, with greater benefits observed in those with established cardiovascular disease (2.0 years) compared to those with only risk factors (0.2 years).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Estimated Life-Years Gained Free of New or Recurrent Major Cardiovascular Events With the Addition of Semaglutide to Standard of Care in People With Type 2 Diabetes and High Cardiovascular Risk. Westerink, J., Matthiessen, KS., Nuhoho, S., et al.[2023]

Oral semaglutide (Rybelsus®) has been shown to provide better glycaemic control and promote weight loss in patients with type 2 diabetes (T2DM) compared to standard oral glucose-lowering medications, based on data from the PIONEER clinical trial program involving 9543 patients.

The safety profile of oral semaglutide is similar to other GLP-1 receptor agonists, and it demonstrated cardiovascular safety comparable to placebo in high-risk patients, making it a viable option for T2DM management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Oral semaglutide, first oral GLP-1 receptor agonist (Rybelsus®)]. Paquot, N.[2022]

In a study of 20 patients with type 2 diabetes in Slovenia, oral semaglutide significantly reduced HbA1c levels and fasting plasma glucose, indicating its efficacy in improving glycaemic control.

Patients reported high satisfaction with the treatment, and while some experienced mild gastrointestinal side effects, the overall safety profile was considered good, suggesting that oral semaglutide is a promising option for diabetes management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy, safety, and patient satisfaction with oral semaglutide: first single-centre clinical experience. Janić, M., Jovanović, M., Janež, A., et al.[2023]

In a study of 112 patients with Type 2 diabetes in Pakistan, Semaglutide significantly reduced HbA1c levels by an average of 1.2% and weight by 4.0 kg after at least 3 months of treatment, demonstrating its efficacy in this population.

Despite some gastrointestinal side effects like dyspepsia and nausea, 72.3% of patients reported satisfaction with Semaglutide, indicating a favorable tolerability profile for this anti-diabetic medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Tolerability of Semaglutide in Patients With Type-2 Diabetes Mellitus: Experience of a Tertiary Care Hospital, Pakistan. Wajid, M., Sattar, S., Khalid, F., et al.[2023]

Oral semaglutide, the first oral GLP-1 receptor agonist approved for type 2 diabetes, has a similar efficacy and safety profile to other GLP-1RAs, making it a viable treatment option for patients.

Patients must take oral semaglutide on an empty stomach and follow specific dosing instructions to maximize its effectiveness and minimize gastrointestinal side effects, which are the most common adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of type 2 diabetes with oral semaglutide: Practical guidance for pharmacists. Kane, MP., Triplitt, CL., Solis-Herrera, CD.[2022]

Subcutaneous semaglutide, a glucagon-like peptide-1 receptor agonist, has been shown to provide superior and sustained glycemic control and weight loss in over 8000 patients with type 2 diabetes, as demonstrated in the SUSTAIN clinical trial program.

In the SUSTAIN 6 trial, semaglutide significantly reduced the risk of cardiovascular events in patients at high risk, indicating its cardiovascular safety and efficacy compared to placebo and standard care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy, safety, and cardiovascular outcomes with once-weekly subcutaneous semaglutide in the treatment of type 2 diabetes: Insights from the SUSTAIN 1-7 trials. Aroda, VR., Ahmann, A., Cariou, B., et al.[2020]

References

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

Semaglutide (SUSTAIN and PIONEER) reduces cardiovascular events in type 2 diabetes across varying cardiovascular risk. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Cardiovascular safety of oral semaglutide in patients with type 2 diabetes: Rationale, design and patient baseline characteristics for the PIONEER 6 trial. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Semaglutide for the Management of Obese Patients With Type 2 Diabetes and Chronic Heart Failure in Real-World Clinical Practice. [2022]

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

In patients with HFpEF and obesity, semaglutide increased weight loss and reduced symptoms and physical limitations at 52 wk. [2023]

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

Estimated Life-Years Gained Free of New or Recurrent Major Cardiovascular Events With the Addition of Semaglutide to Standard of Care in People With Type 2 Diabetes and High Cardiovascular Risk. [2023]

6. Belgium pubmed.ncbi.nlm.nih.gov

[Oral semaglutide, first oral GLP-1 receptor agonist (Rybelsus®)]. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Efficacy, safety, and patient satisfaction with oral semaglutide: first single-centre clinical experience. [2023]

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

Efficacy and Tolerability of Semaglutide in Patients With Type-2 Diabetes Mellitus: Experience of a Tertiary Care Hospital, Pakistan. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Management of type 2 diabetes with oral semaglutide: Practical guidance for pharmacists. [2022]

10. France pubmed.ncbi.nlm.nih.gov

Comparative efficacy, safety, and cardiovascular outcomes with once-weekly subcutaneous semaglutide in the treatment of type 2 diabetes: Insights from the SUSTAIN 1-7 trials. [2020]