314 Participants Needed

Metformin for Abdominal Aortic Aneurysm

(LIMIT Trial)

SS
RD
SS
SS
Overseen BySohrab Sami
Prior Safety DataThis treatment has passed at least one previous human trial
Approved in 6 JurisdictionsThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

In this research, the investigators are looking at the effects of a drug called metformin may have on the growth of abdominal aortic aneurysm (AAA)s. AAA is an abnormal enlargement of the aorta, which is the large artery in the abdomen (stomach area). The enlargement of the aorta carries a risk that it will rupture and cause life-threatening bleeding in the abdomen (belly). In this study the investigators hope to learn how metformin is associated with the enlargement or change in size of the AAA in study participants. Smaller studies have suggested that metformin may reduce the rate at which aortic aneurysms enlarge. This study will test this question: does metformin prevent AAAs from growing larger?

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 taking medications for diabetes. It's best to discuss your current medications with the trial team to see if they might affect your eligibility.

What evidence supports the effectiveness of the drug Metformin for treating abdominal aortic aneurysm?

Research suggests that Metformin, a common diabetes medication, may help slow the growth of abdominal aortic aneurysms and reduce the risk of complications, as seen in studies involving diabetic patients.12345

Is Metformin generally safe for humans?

Metformin, also known as Glucophage, is widely used and generally considered safe for treating conditions like type 2 diabetes and gestational diabetes. It is often combined with other medications, like sitagliptin, to improve blood sugar control, and has been approved by the FDA for these uses.678910

How does the drug metformin differ from other treatments for abdominal aortic aneurysm?

Metformin is unique because it is primarily used as a diabetes medication but has shown potential in slowing the growth of abdominal aortic aneurysms, which is not a standard treatment for this condition. Unlike other treatments, metformin may reduce the risk of aneurysm enlargement and rupture-related mortality, offering a novel approach to managing this condition.123511

Research Team

RD

Ronald Dalman, MD

Principal Investigator

Stanford University

Eligibility Criteria

The LIMIT trial is for men and women aged 55 to 90 with abdominal aortic aneurysms measuring 35-49 mm (men) or 35-45 mm (women). Participants must have stable blood sugar levels (HgbA1c ≤ 6.5%), good kidney function, and be able to take oral medication. Women of childbearing age must use effective contraception.

Inclusion Criteria

My kidney function is good enough to start and continue the trial.
I am between 55 and 95 years old.
For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening, with an agreement to use such a method of contraception during study participation and for an additional 4 weeks after the end of study drug administration.
See 14 more

Exclusion Criteria

You have very low levels of hemoglobin in your blood, less than 10 grams per deciliter.
For female participants of childbearing potential: pregnancy, intent to become pregnant, lactation, or unwilling or unable to use an effective method of contraception
I have had or will have surgery for an abdominal aortic aneurysm.
See 11 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive metformin or placebo, with dosage increasing weekly over the first month

2 years
Regular visits for monitoring and dosage adjustments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

  • Metformin
  • Placebo
Trial OverviewThis study tests whether metformin can prevent the growth of abdominal aortic aneurysms compared to a placebo. Participants will receive either metformin or a placebo and undergo CT scans at the start and end of the study to measure any changes in their aneurysm size.
Participant Groups
2Treatment groups
Active Control
Placebo Group
Group I: Metformin groupActive Control1 Intervention
Participants will either be assigned to take metformin 500 mg tablet(s) daily or identical tablet(s) that contain no active drug, also taken every day. Over the first four weeks of the study, you will increase your dosage every week by one pill, so at the end of the first month you will be taking up to four pills per day. If you develop any symptoms or side effects from pill ingestion during this process, your dose will be decreased to the last number of pills you were able to take without developing side effects.
Group II: Placebo GroupPlacebo Group1 Intervention
Participants will either be assigned to take metformin 500 mg tablet(s) daily or identical tablet(s) that contain no active drug, also taken every day. Over the first four weeks of the study, you will increase your dosage every week by one pill, so at the end of the first month you will be taking up to four pills per day. If you develop any symptoms or side effects from pill ingestion during this process, your dose will be decreased to the last number of pills you were able to take without developing side effects.

Metformin is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

🇪🇺
Approved in European Union as Glucophage for:
  • Type 2 diabetes
🇺🇸
Approved in United States as Glucophage for:
  • Type 2 diabetes
🇨🇦
Approved in Canada as Glucophage for:
  • Type 2 diabetes
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Approved in Japan as Glucophage for:
  • Type 2 diabetes
🇨🇳
Approved in China as Glucophage for:
  • Type 2 diabetes
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Approved in Switzerland as Glucophage for:
  • Type 2 diabetes

Find a Clinic Near You

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials
2,527
Recruited
17,430,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials
3,987
Recruited
47,860,000+

VA Palo Alto Health Care System

Collaborator

Trials
97
Recruited
58,500+

Kaiser Permanente

Collaborator

Trials
563
Recruited
27,400,000+

Findings from Research

In a study involving 266 patients, metformin use in diabetics did not show any significant differences in inflammatory markers or immune cell profiles related to abdominal aortic aneurysm (AAA) formation and growth.
The research indicates that metformin does not appear to influence the peripheral inflammatory environment in patients at risk for or diagnosed with AAA, suggesting that its protective effects against AAA may not be mediated through changes in inflammation.
Metformin does not reduce inflammation in diabetics with abdominal aortic aneurysm or at high risk of abdominal aortic aneurysm formation.Wang, SK., Green, LA., Gutwein, AR., et al.[2018]
In a study of 13,834 patients with abdominal aortic aneurysm (AAA) over an average follow-up of 4.2 years, metformin use was associated with a significant 20% reduction in the yearly growth rate of AAA compared to non-users.
The analysis suggests that metformin may be a promising therapy to limit AAA progression, warranting further clinical trials to explore its efficacy in early AAA disease management.
Metformin prescription status and abdominal aortic aneurysm disease progression in the U.S. veteran population.Itoga, NK., Rothenberg, KA., Suarez, P., et al.[2022]
Metformin significantly reduces the progression of established abdominal aortic aneurysms (AAA) in mice, showing an 85% reduction at 3 days and 68% at 10 days after treatment initiation compared to controls.
The mechanism of action involves AMPK activation, which helps preserve elastin and smooth muscle cells while reducing inflammation, specifically by limiting the differentiation of interferon-γ-producing T cells.
Mechanisms and efficacy of metformin-mediated suppression of established experimental abdominal aortic aneurysms.Xu, B., Li, G., Li, Y., et al.[2023]

References

Metformin does not reduce inflammation in diabetics with abdominal aortic aneurysm or at high risk of abdominal aortic aneurysm formation. [2018]
Metformin prescription status and abdominal aortic aneurysm disease progression in the U.S. veteran population. [2022]
Mechanisms and efficacy of metformin-mediated suppression of established experimental abdominal aortic aneurysms. [2023]
Metformin Prescription Associated with Reduced Abdominal Aortic Aneurysm Growth Rate and Reduced Chemokine Expression in a Swedish Cohort. [2021]
Association of Metformin and Abdominal Aortic Aneurysm Repair Outcomes. [2022]
Glucagon-Like Peptide-1 Receptor Agonists in Type 2 Diabetes Mellitus and Cardiovascular Disease: The Past, Present, and Future. [2022]
Janumet: a combination product suitable for use in patients with Type 2 diabetes. [2019]
Glucagon-Like Peptide-1 Receptor Agonists and Cardiovascular Risk Reduction in Type 2 Diabetes Mellitus: Is It a Class Effect? [2019]
9.United Arab Emiratespubmed.ncbi.nlm.nih.gov
Efficacy and Cardiovascular Safety of GLP-1 Receptor Analogues. [2021]
Glibenclamide and metfoRmin versus stAndard care in gEstational diabeteS (GRACES): a feasibility open label randomised trial. [2021]
Association Between Metformin and Abdominal Aortic Aneurysm: A Meta-Analysis. [2022]