175 Participants Needed

Metformin + Lifestyle Changes for Atrial Fibrillation

(TRIM-AF Trial)

MK
NV
LL
Overseen ByLuke Laffin, MD
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

Trial Summary

What is the purpose of this trial?

Prospective randomized open-label blinded endpoint (PROBE) 2x2 factorial study of metformin extended release up to 750 mg BID and lifestyle and risk factor modification (LRFM) in CIED patients with at least 1 ≥5 minute episode of AF over the prior 3 months. Randomization will be stratified by pacemaker vs. ICD and rhythm at enrollment (sinus rhythm/atrial paced vs. 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 you must not be on metformin or certain other drugs like anti-retroviral protease inhibitors or topiramate. If you're on an antiarrhythmic drug, you should have been on a stable regimen for the past 3 months.

What data supports the effectiveness of the treatment Metformin + Lifestyle Changes for Atrial Fibrillation?

While there is no direct evidence from the provided research about Metformin and lifestyle changes specifically for atrial fibrillation, lifestyle modifications have been shown to help manage risk factors for cardiovascular diseases, which can be related to atrial fibrillation. Additionally, Metformin is commonly used to manage type 2 diabetes, which is a risk factor for cardiovascular issues.12345

Is Metformin safe for humans?

Metformin is generally considered safe for humans and is widely used as the first-line treatment for type 2 diabetes. It has proposed benefits like reducing inflammation and protecting the heart, and no major safety concerns have been raised in recent studies.678910

How does the treatment of Metformin combined with lifestyle changes for atrial fibrillation differ from other treatments?

This treatment is unique because it combines Metformin, a drug commonly used for type 2 diabetes, with lifestyle changes to address atrial fibrillation, a heart condition. The novelty lies in using a diabetes medication to potentially benefit heart health, alongside lifestyle modifications that have shown success in managing chronic diseases.1112131415

Research Team

MK

Mina K Chung, MD

Principal Investigator

The Cleveland Clinic

Eligibility Criteria

This trial is for adults with a pacemaker or ICD who've had at least one episode of atrial fibrillation in the past 3 months. They should not be on diabetes medication, have moderate renal disease, significant alcohol use, or life expectancy less than 2 years. Pregnant women and those unable to follow study protocols are also excluded.

Inclusion Criteria

You have a pacemaker or ICD with certain features for monitoring heart function.
You have not had atrial fibrillation recorded on your heart monitoring device in the past 6 months.
I have irregular heartbeats and plans to normalize it.
See 4 more

Exclusion Criteria

I am not pregnant, breastfeeding, or if capable of childbearing, I am willing to use contraception.
I have permanent atrial fibrillation and no plans to change it.
You drink more than two alcoholic drinks on average every day.
See 14 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive metformin extended release up to 750 mg twice daily and/or lifestyle and risk factor modification

3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, including changes in AF burden and other health metrics

Up to 2 years

Treatment Details

Interventions

  • Lifestyle/Risk Factor Modification
  • Metformin
Trial Overview The TRIM-AF study tests if Metformin and lifestyle changes can help manage Atrial Fibrillation in patients with cardiac devices. Participants will either get Metformin up to 750 mg twice daily or undergo lifestyle modifications, decided randomly.
Participant Groups
5Treatment groups
Experimental Treatment
Active Control
Group I: Metformin + LRFMExperimental Treatment2 Interventions
Metformin ER up to 750 mg twice daily + Lifestyle/Risk Factor Modification (LRFM) diet/nutrition, exercise, and risk factor modification
Group II: MetforminExperimental Treatment1 Intervention
Metformin ER up to 750 mg twice daily
Group III: Lifestyle/Risk Factor ModificationExperimental Treatment1 Intervention
Lifestyle/Risk Factor Modification (LRFM): Diet/nutrition, exercise, and risk factor modification
Group IV: ControlActive Control1 Intervention
Written educational literature on healthy eating and exercise guideline
Group V: No Atrial FibrillationActive Control1 Intervention
Written educational literature on healthy eating and exercise guideline

Find a Clinic Near You

Who Is Running the Clinical Trial?

Mina Chung, MD

Lead Sponsor

Trials
1
Recruited
180+

The Cleveland Clinic

Collaborator

Trials
1,072
Recruited
1,377,000+

American Heart Association

Collaborator

Trials
352
Recruited
6,196,000+

Findings from Research

GLP-1 receptor agonists like liraglutide, dulaglutide, and semaglutide have been shown to significantly reduce the risk of major cardiovascular events in patients with type 2 diabetes at high cardiovascular risk, based on robust cardiovascular outcomes trials.
Current diabetes treatment guidelines emphasize the importance of using medications with proven cardiovascular benefits, such as GLP-1 receptor agonists, rather than solely focusing on blood sugar control.
Cardiovascular Outcomes Trials of Incretin-Based Therapies.Thethi, TK., Bilal, A., Pratley, RE.[2022]
A study of 405 patients with type 2 diabetes showed that both sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are safe to use alongside other glucose-lowering medications over a 12-month period.
The safety evaluation indicated no significant adverse effects on kidney function or liver enzymes, suggesting that these medications can be effectively integrated into standard diabetes treatment regimens without compromising safety.
The Safety Profile of Sodium-Glucose Cotransporter-2 Inhibitors and Glucagon-like Peptide 1 Receptor Agonists in the Standard of Care Treatment of Type 2 Diabetes Mellitus.Salmen, T., Bobirca, FT., Bica, IC., et al.[2023]
Long-acting GLP-1 receptor agonists, such as liraglutide and semaglutide, are effective anti-obesity medications that can lead to significant weight loss, with semaglutide showing an average weight loss of 11.6% after one year, compared to 5.5% with liraglutide.
Both medications are generally well tolerated, with similar safety profiles, though they can cause transient gastrointestinal issues; ongoing long-term studies are needed to further evaluate their efficacy and safety.
Benefit-Risk Assessment of Obesity Drugs: Focus on Glucagon-like Peptide-1 Receptor Agonists.Christensen, RM., Juhl, CR., Torekov, SS.[2020]

References

Insulin glargine provides greater improvements in glycaemic control vs. intensifying lifestyle management for people with type 2 diabetes treated with OADs and 7-8% A1c levels. The TULIP study. [2022]
2019 Update to: Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). [2022]
An Overview of the Burden of Illness and the Role of Once-Weekly Glucagon-like Peptide-1 Receptor Agonists in the Treatment of Type 2 Diabetes. [2019]
Prevention of diabetes and cardiovascular disease in patients with impaired glucose tolerance: rationale and design of the Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) Trial. [2022]
Poor health status, inappropriate glucose-lowering therapy and high one-year mortality in geriatric patients with type 2 diabetes. [2020]
Cardiovascular Outcomes Trials of Incretin-Based Therapies. [2022]
The Safety Profile of Sodium-Glucose Cotransporter-2 Inhibitors and Glucagon-like Peptide 1 Receptor Agonists in the Standard of Care Treatment of Type 2 Diabetes Mellitus. [2023]
Benefit-Risk Assessment of Obesity Drugs: Focus on Glucagon-like Peptide-1 Receptor Agonists. [2020]
Association between first-line monotherapy with metformin and the risk of atrial fibrillation (AMRAF) in patients with type 2 diabetes. [2023]
10.United Arab Emiratespubmed.ncbi.nlm.nih.gov
Efficacy and Cardiovascular Safety of Sulfonylureas. [2021]
[Lifestyle medicine: effective cure or just snake oil?] [2020]
Prevention and current onset delay approaches of type 2 diabetes mellitus (T2DM). [2021]
13.United Statespubmed.ncbi.nlm.nih.gov
Outcomes of health care providers' recommendations for healthy lifestyle among U.S. adults with prediabetes. [2019]
[Lifestyle intervention in the consulting room: high-hanging fruit]. [2020]
15.United Statespubmed.ncbi.nlm.nih.gov
Effects of exenatide combined with lifestyle modification in patients with type 2 diabetes. [2018]