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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether Liraglutide, an injectable medication, can reduce fat deposits around the heart and stabilize atrial fibrillation, a heart rhythm issue. Liraglutide is already known to aid in weight loss. The trial includes two groups: one will follow a structured program to manage weight and other health factors, while the other will do the same plus take Liraglutide. Ideal participants are those with frequent atrial fibrillation episodes, a BMI of 27 or higher, and who are planning a heart procedure called catheter ablation. As a Phase 4 trial, Liraglutide is already FDA-approved and proven effective, and this research aims to understand how it benefits more patients.

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 is the safety track record for Liraglutide?

Research has shown that Liraglutide is generally safe for patients, particularly those at high risk for heart problems. It positively affects the heart and blood vessels. Studies have found that Liraglutide does not increase the risk of major heart issues. The FDA has approved it for weight management in obese adults with related health conditions, indicating its safety for current uses. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike standard treatments for atrial fibrillation, which often focus on managing heart rhythm or rate through medications and procedures like ablation, Liraglutide offers a novel approach by addressing weight management. Liraglutide is unique because it's an FDA-approved medication that aids in weight loss by mimicking a hormone that targets areas of the brain regulating appetite. Researchers are excited about Liraglutide because it not only helps in chronic weight management but also potentially mitigates risk factors associated with atrial fibrillation, such as obesity and its related conditions. By integrating Liraglutide with risk factor modification programs, there's potential for a comprehensive strategy that not only addresses heart rhythm issues but also tackles underlying weight-related causes.

What is the effectiveness track record for Liraglutide in reducing fat deposits and stabilizing atrial fibrillation?

Research has shown that liraglutide can assist people with atrial fibrillation (AF), particularly when combined with a program to reduce risk factors. In this trial, one group of participants will receive a structured risk factor modification (RFM) program, while another group will receive both RFM and liraglutide. One study found that 83% of patients who used both liraglutide and risk management were free of AF after a year. This combination also resulted in significant weight loss, which is crucial because losing fat around the heart can help manage AF. Liraglutide is already approved for weight management, which may aid in stabilizing AF. These findings suggest that liraglutide, along with lifestyle changes, offers a promising approach to reducing and possibly eliminating AF episodes. ^{3 6 7 8 9}

Who Is on the Research Team?

Jeffrey Goldberger, MD

Principal Investigator

University of Miami

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 (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]

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, 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]

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 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]

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]

Citations

1. healio.com healio.com/news/cardiology/20231207/liraglutide-plus-risk-factor-modification-improves-freedom-from-af-after-ablation-leaf

Liraglutide plus risk factor modification improves freedom ... Adults with obesity and atrial fibrillation treated with liraglutide plus risk factor modification had improved outcomes after catheter ablation.

2. heartrhythmjournal.com heartrhythmjournal.com/article/S1547-5271(25)00517-X/fulltext

PO-01-030 LONG-TERM ABLATION OUTCOMES IN THE ... In LEAF, obese patients undergoing AF ablation had significant weight loss at 1 year with both RFM and RFM+L, but much more favorable outcomes ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10880291/

Feasibility study of Glucagon-like peptide-1 analogues for ... This study will allow us to determine whether the use of liraglutide in obese patients with atrial fibrillation undergoing ablation is feasible ...

4. news.med.miami.edu news.med.miami.edu/leaf-atrial-fibrillation/

AHA Scientific Sessions Feature Miller School's Pioneering ... Eighty-three percent of those who implemented both liraglutide and risk management were free of atrial fibrillation after a year, whereas the ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03856632

NCT03856632 | Liraglutide Effect in Atrial Fibrillation The investigator is conducting this study to find out if Liraglutide will reduce the fat deposits surrounding the participant's heart, and stabilize (and ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10136170/

New Insights into the Use of Liraglutide—Impact ... Liraglutide has beneficial effects on the cardiovascular system; patients with high cardiovascular risk particularly benefit from treatment.

7. ahajournals.org ahajournals.org/doi/10.1161/CIRCEP.125.014069

Effect of Semaglutide on Atrial Arrhythmias Recurrence ... During the 12-month follow-up, the semaglutide group showed a higher event-free rate for recurrent atrial arrhythmias (hazard ratio, 0.68 [95% ...

8. ajmc.com ajmc.com/view/obesity-therapy-saxenda-gets-cardiovascular-safety-indication

Obesity Therapy Saxenda Gets Cardiovascular Safety ... The label now includes clinical data from the LEADER trial, which found that the 1.8-mg dose of liraglutide did not increase the risk of major ...

9. academic.oup.com academic.oup.com/eurjpc/advance-article/doi/10.1093/eurjpc/zwaf257/8121325

Reduction of new onset of atrial fibrillation in patients treated ... For these many reasons, semaglutide therapy may provide protective effects against the onset of AF. Previous studies have reported conflicting results on the ...