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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether weight loss through semaglutide (also known as Ozempic, Wegovy, or Rybelsus), combined with lifestyle counseling, can improve symptoms for individuals with a type of heart failure linked to obesity. Participants will receive either semaglutide or a placebo once a week, along with guidance on healthy living. Suitable candidates have a BMI of 30 or more and have been diagnosed with heart failure where the heart pumps normally but struggles to fill with blood. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

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.

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

Studies have shown that semaglutide is generally well-tolerated. In a large study, fewer participants taking semaglutide experienced major heart problems compared to those not taking it. Specifically, 6.5% of patients on semaglutide had heart issues, while 8% of those not on the drug did. Another study found that semaglutide reduced hospital visits related to heart failure by 76%. These findings suggest that semaglutide is relatively safe for heart-related conditions.

However, semaglutide can still cause side effects. Some individuals may experience nausea, vomiting, or diarrhea. It is always best to consult a healthcare provider about any concerns before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about semaglutide for heart failure because it offers a novel approach compared to traditional treatments, which typically focus on managing symptoms like fluid retention and blood pressure. Semaglutide, originally used for diabetes, is unique because it targets metabolic pathways by mimicking a hormone called GLP-1, which helps regulate blood sugar and may improve heart function. This different mechanism of action could lead to better outcomes for heart failure patients, potentially addressing underlying causes rather than just symptoms. Additionally, semaglutide is administered once weekly, which could improve patient adherence compared to daily medications.

What evidence suggests that this trial's treatments could be effective for obesity-related cardiomyopathy?

Research has shown that semaglutide can improve heart health. In individuals with heart failure, semaglutide enhanced all health measures compared to those without heart failure. It reduced the risk of heart failure events and death related to cardiovascular issues. Another study found that semaglutide lowered the risk of major heart problems, such as heart attacks and strokes. In this trial, participants will receive either semaglutide or a placebo, along with counseling on healthy lifestyle interventions. Overall, semaglutide has shown promise in reducing heart-related issues, making it a strong option for treating heart failure related to obesity. ^{1 2 6 7 8}

Who Is on the Research Team?

Barry Borlaug, MD

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

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

LVEF ≥ 50% within the preceding year

I have moderate to severe heart condition symptoms.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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 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]

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]

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]

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]

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]

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]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2307563

Semaglutide and Cardiovascular Outcomes in Obesity ... A primary cardiovascular end-point event occurred in 569 of the 8803 patients (6.5%) in the semaglutide group and in 701 of the 8801 patients (8.0%) in the ...

2. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(24)01498-3/fulltext

a prespecified analysis of the SELECT trial Semaglutide improved all outcome measures in patients with heart failure at random assignment compared with those without heart failure (HR 0·72 ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39217553/

Effects of Semaglutide on Heart Failure Outcomes in ... Conclusions: Semaglutide substantially reduced the risk of time to first composite outcome of HF events or CV death, as well as HF events and CV ...

4. becarispublishing.com becarispublishing.com/digital-content/blog-post/real-world-data-show-novo-nordisk-s-semaglutide-outperforms-eli-lilly-s-tirzepatide

Real-world data shows Novo Nordisk's semaglutide ... Novo Nordisk has reported that Wegovy reduced the risk of heart attack, stroke, or death by 57% compared with tirzepatide in patients with ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0140673624014983

Semaglutide and cardiovascular outcomes in patients with ... Semaglutide reduced MACE, heart failure composite, cardiovascular death, and all-cause death in patients with atherosclerotic cardiovascular ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39396098/

Semaglutide effects on safety and cardiovascular ... Conclusion: The use of semaglutide reduced 76% in hospitalization due to HF, 17% deaths due to cardiovascular causes, 21% deaths due to any ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40786355/

Semaglutide in Heart Failure With Preserved Ejection ... Semaglutide significantly improves HFpEF outcomes in obese patients, with STEP HFpEF (n = 529) and STEP HFpEF DM (n = 616) demonstrating Kansas ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S0735109724081166

Effects of Semaglutide on Heart Failure Outcomes in ... This prespecified analysis of the FLOW trial demonstrated that semaglutide decreased a composite outcome of time to first HF events or CV death by 27%, HF ...