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

Trial Summary

What is the purpose of this trial?

The goal of the study is to learn how a weight loss medication called semaglutide, which is used to treat obesity, in addition to standard AF treatment might affect AF, atrial fibrillation severity, and whether it changes the risk of atrial fibrillation recurring after standard AF treatments.

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.

What data supports the effectiveness of the drug Semaglutide for treating atrial fibrillation?

Semaglutide has been shown to effectively control blood sugar levels and promote weight loss in people with type 2 diabetes, which may indirectly suggest potential benefits for heart health, as better blood sugar control and weight management can reduce cardiovascular risks. ^{1 2 3 4 5}

Is semaglutide safe for humans?

Semaglutide, used under names like Ozempic, Wegovy, and Rybelsus, has been tested in people with type 2 diabetes and is generally considered safe. It has a tolerability profile similar to other drugs in its class and has been shown to be safe for the heart in high-risk patients. ^{1 2 3 4 6}

How does the drug Semaglutide differ from other drugs for atrial fibrillation?

Semaglutide is unique because it is primarily known for treating diabetes and weight management, not atrial fibrillation, which makes its use for this condition novel. Unlike traditional antiarrhythmic drugs that target ion channels in the heart, Semaglutide works by mimicking a hormone that regulates blood sugar and appetite, suggesting a different mechanism of action for atrial fibrillation. ^{7 8 9 10 11}

Research Team

Silvana Pannain, MD

Principal Investigator

University of Chicago

Eligibility Criteria

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

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

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

I have a history of type I diabetes.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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, 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]

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]

References

1. Belgium pubmed.ncbi.nlm.nih.gov

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

2. Belgium pubmed.ncbi.nlm.nih.gov

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

3. 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]

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

Efficacy and safety of oral semaglutide by subgroups of patient characteristics in the PIONEER phase 3 programme. [2022]

5. England 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. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Gastrointestinal disorders potentially associated with Semaglutide: an analysis from the Eudravigilance Database. [2023]

7. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Pharmacological treatment of atrial fibrillation: mechanisms of action and efficacy of class III drugs. [2019]

8. Italy pubmed.ncbi.nlm.nih.gov

[New antiarrhythmic drugs for the treatment of atrial fibrillation]. [2018]

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

Recent advances in arrhythmia therapy: treatment and prevention of atrial fibrillation. [2022]

10. Germany pubmed.ncbi.nlm.nih.gov

Atrial-selective drugs for treatment of atrial fibrillation. [2021]

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

Atrial fibrillation: from ion channels to bedside treatment options. [2009]