Liraglutide for Atrial Fibrillation

(LEAF Trial)

Overseen By Carmen M Baez-Garcia, RN

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Miami

Must not be taking: Glitazones, SGLT2i, GLP-1 analogs, DPP4 inhibitors

Disqualifiers: Longstanding AF, Type 1 diabetes, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 3 months

60 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal (or purpose) of this study is to evaluate (study) a new way to stabilize (steady) the activity between the fat deposits surrounding the heart and the left atrium. To reduce the amount of EAT, this study will use a medication called Liraglutide. This medication is known to work on fat deposits and produce weight loss. The investigator is conducting this study to find out if Liraglutide will reduce the fat deposits surrounding the participant's heart, and stabilize (and perhaps reduce or eliminate) atrial fibrillation activity.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are using certain diabetes medications like glitazones, SGLT2 inhibitors, other GLP-1 analogs, or DPP4 inhibitors.

What data supports the effectiveness of the drug Liraglutide for atrial fibrillation?

Liraglutide is effective in managing type 2 diabetes and obesity by helping control blood sugar levels and reducing appetite, which may indirectly benefit heart health. However, there is no direct evidence from the provided research that supports its effectiveness specifically for atrial fibrillation. ^{1 2 3 4 5}

Is liraglutide safe for humans?

Liraglutide, used under the names Victoza and Saxenda, has been shown to be generally safe in humans for treating type 2 diabetes and obesity. Common side effects include nausea, which usually goes away over time, and the risk of low blood sugar is low. ^{1 2 3 4 6}

How is the drug Liraglutide unique for treating atrial fibrillation?

Liraglutide is unique because it is primarily known as a treatment for type 2 diabetes and obesity, working by increasing insulin secretion and reducing appetite. Its use for atrial fibrillation is novel, as it is not a standard treatment for this heart condition, and it may offer additional benefits due to its cardiovascular effects. ^{1 3 5 7 8}

Research Team

Jeffrey Goldberger, MD

Principal Investigator

University of Miami

Eligibility Criteria

Adults over 18 with a BMI of at least 27 kg/m2 and persistent or paroxysmal atrial fibrillation, who are planning to undergo catheter ablation and receive care at the University of Miami. Excluded are those with contraindications to Liraglutide, poorly controlled diabetes, pregnant or breastfeeding women, long-term AF over 3 years, unsuitable for ablation, short life expectancy, certain medication users including other GLP-1 analogs or DPP4 inhibitors.

Inclusion Criteria

I want to have a procedure to treat my irregular heartbeat.

Receiving follow-up care at the University of Miami

My AFib lasts for more than 7 days or stops on its own within 7 days.

Exclusion Criteria

You have had a serious allergic reaction to liraglutide.

My type 2 diabetes is not well-managed, with an HbA1c over 10%.

I have recovered from any serious illness or treatments I received more than 4 weeks ago.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Liraglutide in addition to a structured risk factor modification program

3 months

Regular visits for monitoring and administration

Catheter Ablation Procedure

Blood samples collected from left atrium and peripheral vessel; ablation procedure conducted

Single procedure

1 visit (in-person)

Follow-up

Participants are monitored for changes in atrial function and inflammation markers

1 year

Periodic visits for echocardiography and biomarker assessment

Treatment Details

Interventions

• Liraglutide

Trial Overview The trial is testing whether Liraglutide can reduce epicardial adipose tissue (EAT) around the heart and stabilize atrial fibrillation. Participants will be given Liraglutide alongside their planned catheter ablation procedure for AFib treatment.

Participant Groups

Group I: RFM plus Liraglutide Experimental Treatment 4 Interventions

In addition to RFM, Liraglutide will be administered. Liraglutide is an FDA approved medication used as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management of obese adults with weight-related comorbid conditions.

Group II: Risk Factor Modification (RFM) Active Control 3 Interventions

A structured risk factor modification (RFM) program currently offered to all patients who are overweight or obese undergoing an ablation procedure for atrial fibrillation.The RFM program is already offered through our Center for Atrial Fibrillation and is managed by a nurse practitioner. The RFM program will provide patient teaching and education on weight, fitness,blood pressure control, glucose control, cholesterol, sleep apnea, smoking, and alcohol.

Liraglutide is already approved in United States, European Union for the following indications:

Approved in United States as Victoza for:

• Type 2 diabetes mellitus treatment
• Cardiovascular risk reduction in adults with type 2 diabetes and heart disease

Approved in United States as Saxenda for:

• Weight loss treatment in adults and children aged 12 and older with obesity

Approved in European Union as Victoza for:

• Type 2 diabetes mellitus treatment
• Cardiovascular risk reduction in adults with type 2 diabetes and heart disease

Approved in European Union as Saxenda for:

• Weight loss treatment in adults and children aged 12 and older with obesity

Who Is Running the Clinical Trial?

University of Miami

Lead Sponsor

Trials

976

Recruited

423,000+

Findings from Research

Liraglutide, approved for Type 2 diabetes and chronic weight management, works by increasing insulin secretion and decreasing appetite, which helps promote weight loss.

Recent findings suggest that liraglutide may also protect against prediabetes and prevent bone loss by enhancing bone formation after weight loss, highlighting its broader health benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liraglutide for Type 2 diabetes and obesity: a 2015 update. Iepsen, EW., Torekov, SS., Holst, JJ.[2015]

Liraglutide (Saxenda) has been shown to effectively promote weight loss in overweight and obese patients, with a higher percentage achieving 5% and 10% weight loss compared to placebo and orlistat, based on randomized controlled studies.

The medication is generally safe, with gastrointestinal side effects being the most common and typically dose-dependent, making it a viable adjunct to lifestyle changes for obesity management, especially in patients with prediabetes and women with PCOS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liraglutide: an injectable option for the management of obesity. Clements, JN., Shealy, KM.[2022]

Liraglutide, now available at a higher dose of 3.0 mg for treating obesity, has been shown to effectively control appetite and promote weight loss when combined with diet and exercise, based on results from the SCALE studies.

The drug is already established for managing type 2 diabetes at lower doses, and its mechanism of action includes effects on the endocrine pancreas and appetite regulation in the hypothalamus, indicating a dual benefit for patients with obesity and diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[LIRAGUTIDE AT A DOSE OF 3.0 MG (SAXENDA): NEW INDICATION FOR THE TREATMENT OF OBESITY]. Scheen, AJ.[2016]

In a study of 225 patients prescribed Saxenda and Victoza, 96% and 98.7% of prescriptions, respectively, were in line with approved indications, indicating high adherence to guidelines.

Only 5% of patients using Saxenda for 16 weeks or longer were non-adherent to the stopping rule, suggesting that these medications are being used safely and effectively in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigating the potential non-authorized use of two different formulations of liraglutide in Europe: A real-world drug utilization study. Sbraccia, P., Aberle, J., Olsen, AH., et al.[2023]

Liraglutide (Victoza) was approved by the US FDA in January 2010 as a treatment to help improve blood sugar control in adults with type 2 diabetes.

As a glucagon-like peptide 1 receptor agonist, liraglutide works by mimicking the effects of a hormone that helps regulate blood sugar levels, making it an effective option for managing diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liraglutide. Drucker, DJ., Dritselis, A., Kirkpatrick, P.[2021]

Liraglutide is an effective treatment for type 2 diabetes, reducing hemoglobin A1c levels by 0.8% to 1.5%, and is safe for patients at risk of hypoglycemia due to its low incidence of this side effect.

It is particularly beneficial for overweight or obese patients, as it not only helps control blood sugar but also promotes weight loss of about 2%-4% of initial body weight, although nausea can occur but is typically manageable with careful dosing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical pearls for initiating and utilizing liraglutide in patients with type 2 diabetes. Gross, B.[2015]

Liraglutide is an FDA-approved GLP-1 receptor agonist for treating type 2 diabetes, administered via subcutaneous injection, and can be used alone or with certain oral medications like metformin or glimepiride.

It is important to note that liraglutide is not recommended as a first-line treatment and is not approved for use in combination with insulin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liraglutide (Victoza) for type 2 diabetes. [2015]

References

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

Liraglutide for Type 2 diabetes and obesity: a 2015 update. [2015]

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

Liraglutide: an injectable option for the management of obesity. [2022]

3. Belgium pubmed.ncbi.nlm.nih.gov

[LIRAGUTIDE AT A DOSE OF 3.0 MG (SAXENDA): NEW INDICATION FOR THE TREATMENT OF OBESITY]. [2016]

4. England pubmed.ncbi.nlm.nih.gov

Investigating the potential non-authorized use of two different formulations of liraglutide in Europe: A real-world drug utilization study. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Liraglutide. [2021]

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

Clinical pearls for initiating and utilizing liraglutide in patients with type 2 diabetes. [2015]

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

Liraglutide (Victoza) for type 2 diabetes. [2015]

8. Czech Republic pubmed.ncbi.nlm.nih.gov

[Victoza changes diabetes and lives of patients 5 years already]. [2022]