Semaglutide for Atrial Fibrillation

(SEMINAL-AF Trial)

Recruiting at 1 trial location

Overseen By Silvana Pannain, MD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University of Chicago

Must not be taking: GLP-1 RA, DPP4-inhibitors

Disqualifiers: Type I diabetes, Active malignancy, 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 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 68 weeks

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether the weight loss medication semaglutide can reduce the severity of atrial fibrillation (AF), a common heart rhythm disorder, when used alongside standard treatments. Researchers aim to determine if semaglutide can lower the chances of AF recurrence after treatment. Participants will receive either semaglutide or a placebo (a harmless pill with no active medication) to compare effects. Suitable candidates have a body mass index (BMI) over 30 and experience either paroxysmal (occasional) or persistent AF, with or without plans for a specific heart procedure called catheter ablation in the next year. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to advancing treatment options for AF.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that certain diabetes medications may need to be adjusted. If you are taking GLP-1 RA, DPP4-inhibitors, or antiobesity medications, you cannot participate if you've used them in the last 90 days.

Is there any evidence suggesting that semaglutide is likely to be safe for humans?

Research has shown that semaglutide is generally safe for use. In studies, only a small number of people taking semaglutide reported serious side effects. For instance, one study found that only 0.9% of participants developed new atrial fibrillation, a type of irregular heartbeat.

Other research suggests that semaglutide might lower the risk of developing atrial fibrillation, indicating that the treatment is not only safe for most people but may also offer additional heart health benefits.

These findings are encouraging, but it's important to weigh both the potential risks and benefits before joining a trial. If there are any concerns, consulting a healthcare professional can be helpful. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for atrial fibrillation?

Semaglutide is unique because it offers a fresh approach to managing atrial fibrillation by utilizing a GLP-1 receptor agonist, traditionally used for diabetes and weight management. Unlike standard treatments like beta-blockers or anticoagulants that focus on controlling heart rate or preventing blood clots, semaglutide targets metabolic pathways, potentially addressing underlying factors contributing to atrial fibrillation. Researchers are excited about semaglutide because it might offer a dual benefit – managing atrial fibrillation while also positively impacting weight and metabolic health, which are often related to cardiovascular conditions.

What evidence suggests that semaglutide might be an effective treatment for atrial fibrillation?

In this trial, participants have a 2 in 3 chance of receiving semaglutide. Studies have shown that semaglutide can reduce the risk of atrial fibrillation (AF), an irregular heartbeat. One study found that people taking semaglutide experienced fewer repeat episodes of abnormal heart rhythms compared to those not taking it. Another analysis found that semaglutide improved quality of life and health outcomes for those with AF. Additionally, research suggests that semaglutide may lower the chance of developing AF initially. Overall, these findings suggest semaglutide might be effective in managing atrial fibrillation and its symptoms. Participants also have a 1 in 3 chance of receiving a placebo in this trial. ^{1 2 6 7 8}

Who Is on the Research Team?

Silvana Pannain, MD

Principal Investigator

University of Chicago

Are You a Good Fit for This Trial?

This trial is for individuals with obesity and atrial fibrillation (AF), a type of irregular heartbeat. Participants should be seeking treatment for AF and are interested in how weight loss might affect their condition.

Inclusion Criteria

BMI greater than or equal to 30 kg/m2

I will follow a specific plan for adjusting my diabetes medication during the study.

Ability to provide informed consent before any trial-related activities

Exclusion Criteria

Uncontrolled thyroid disease: TSH (Thyroid-stimulating hormone) > 10.0 mIU/L or < 0.4 mIU/L at screening

I have not had a pulmonary embolism in the last 90 days.

I have a history of type I diabetes.

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 to assess the impact on atrial fibrillation and weight loss

68 weeks

Regular outpatient monitoring visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Semaglutide

Trial Overview The study is testing the effects of semaglutide, a medication used for weight loss, on patients with AF. It aims to see if this drug, alongside standard AF treatments, can reduce the severity of AF or prevent it from coming back.

How Is the Trial Designed?

Group I: Semaglutide Active Control 1 Intervention

Participants will have a 2 in 3 chance of receiving semaglutide (2.4 mg).

Group II: Placebo Placebo Group 1 Intervention

Participants will have a 1 in 3 chance of receiving placebo.

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?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Published Research Related to This Trial

Semaglutide (Ozempic®) is an effective once-weekly treatment for type 2 diabetes, showing superior glucose-lowering effects and greater weight loss compared to other GLP-1 receptor agonists in Phase III clinical trials.

It is approved for use in Belgium for patients with type 2 diabetes who have not achieved adequate control with other antidiabetic therapies, particularly in those with a body mass index of 30 kg/m² or higher.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Semaglutide, once weekly GLP-1 receptor agonist (Ozempic®)]. Scheen, AJ.[2019]

In the SUSTAIN 1 to 5 trials involving 3918 participants with type 2 diabetes, semaglutide significantly helped more individuals achieve their HbA1c targets (47% to 74%) compared to placebo (7% to 19%) and other active comparators (16% to 29%).

Semaglutide was effective in achieving these results while minimizing unwanted outcomes, such as weight gain, severe hypoglycaemia, and gastrointestinal side effects, making it a safer option for managing type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Achieving glycaemic control without weight gain, hypoglycaemia, or gastrointestinal adverse events in type 2 diabetes in the SUSTAIN clinical trial programme. DeVries, JH., Desouza, C., Bellary, S., et al.[2022]

Semaglutide, a GLP-1 receptor agonist for type 2 diabetes, has a good safety profile but is associated with a high prevalence of gastrointestinal disorders, reported in over 3500 cases (53.2%).

Compared to other diabetes medications like sitagliptin and empagliflozin, semaglutide has a significantly higher number of reported gastrointestinal adverse events, indicating the need for careful monitoring in certain patient subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastrointestinal disorders potentially associated with Semaglutide: an analysis from the Eudravigilance Database. Cabral Lopes, A., Roque, F., Lourenço, O., et al.[2023]

Oral semaglutide, particularly at doses of 14 mg or flexibly dosed, significantly reduced HbA1c levels and body weight in patients with type 2 diabetes compared to other treatments, especially in those with higher baseline HbA1c levels.

The safety profile of oral semaglutide was comparable to that of other treatments, although it was associated with a higher incidence of gastrointestinal adverse events, which were consistent across different patient subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of oral semaglutide by subgroups of patient characteristics in the PIONEER phase 3 programme. Aroda, VR., Bauer, R., Christiansen, E., et al.[2022]

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]

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]

Citations

1. 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% ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39217565/

Atrial Fibrillation and Semaglutide Effects in Obesity-Related ... Semaglutide 2.4 mg improved HF-related symptoms, physical limitations, and exercise function and reduced body weight in patients with obesity-related HFpEF.

3. 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 ... A secondary analysis revealed that semaglutide led to greater improvements in quality of life and clinical outcomes in participants with AF compared to those ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1871402124001280

Semaglutide for the prevention of atrial fibrillation Semaglutide was associated with a reduced risk of atrial fibrillation occurrence in the overall pooled analysis. •. Favorable outcomes were observed in subsets ...

5. jacc.org jacc.org/doi/10.1016/j.jacc.2024.08.023

Atrial Fibrillation and Semaglutide Effects in Obesity ... Semaglutide 2.4 mg improved HF-related symptoms, physical limitations, and exercise function and reduced body weight in patients with obesity-related HFpEF.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11486552/

Atrial Fibrillation and Semaglutide Effects in Obesity ... In participants without AF at baseline, new AF was reported as a serious adverse event in 0.9% (3 of 321) of semaglutide-treated patients and ...

7. acc.org acc.org/About-ACC/Press-Releases/2024/08/30/11/41/Semaglutide-Improves-Heart-Health-Outcomes

Semaglutide Improves Heart Health Outcomes Beyond ... Semaglutide (2.4mg) improved obesity-related HF symptoms in people with inflammation and both with and without atrial fibrillation, plus ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12403603/

Effect of semaglutide on arrhythmic, major cardiovascular, and ... Compared with the controls, semaglutide significantly reduced the risk of atrial fibrillation (AF) (RR 0.79, 95% CI 0.63–0.99), sinus node ...