Metformin for Abdominal Aortic Aneurysm
(LIMIT Trial)
Recruiting in Palo Alto (17 mi)
Overseen byRonald Dalman, MD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Stanford University
Must not be taking: Diabetes medications
Disqualifiers: Diabetes, Metabolic acidosis, Liver disease, others
Prior Safety Data
Approved in 6 Jurisdictions
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.
12345Is 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.
678910How 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.
123511Eligibility 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 β€ 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.
+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.
+11 more
Trial 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
Participant Groups
This 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.
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:
πͺπΊ Approved in European Union as Glucophage for:
- Type 2 diabetes
πΊπΈ Approved in United States as Glucophage for:
- Type 2 diabetes
π¨π¦ Approved in Canada as Glucophage for:
- Type 2 diabetes
π―π΅ Approved in Japan as Glucophage for:
- Type 2 diabetes
π¨π³ Approved in China as Glucophage for:
- Type 2 diabetes
π¨π Approved in Switzerland as Glucophage for:
- Type 2 diabetes
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Stanford Hospital and ClinicsStanford, CA
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Who Is Running the Clinical Trial?
Stanford UniversityLead Sponsor
National Heart, Lung, and Blood Institute (NHLBI)Collaborator
VA Palo Alto Health Care SystemCollaborator
Kaiser PermanenteCollaborator
References
Metformin does not reduce inflammation in diabetics with abdominal aortic aneurysm or at high risk of abdominal aortic aneurysm formation. [2018]The protective effect of diabetes mellitus on abdominal aortic aneurysm formation and growth has been repeatedly observed in population studies but continues to be poorly understood. However, recent investigations have suggested that metformin, a staple antihyperglycemic medication, may be independently protective against abdominal aortic aneurysm formation and growth. Therefore, we describe the effect of metformin in abdominal aortic aneurysm and at-risk patients on markers of inflammation, the driver of early abdominal aortic aneurysm formation and growth.
Metformin prescription status and abdominal aortic aneurysm disease progression in the U.S. veteran population. [2022]Identification of a safe and effective medical therapy for abdominal aortic aneurysm (AAA) disease remains a significant unmet medical need. Recent small cohort studies indicate that metformin, the world's most commonly prescribed oral hypoglycemic agent, may limit AAA enlargement. We sought to validate these preliminary observations in a larger cohort.
Mechanisms and efficacy of metformin-mediated suppression of established experimental abdominal aortic aneurysms. [2023]Metformin treatment attenuates experimental abdominal aortic aneurysm (AAA) formation, as well as reduces clinical AAA diameter enlargement in patients with diabetes. The mechanisms of metformin-mediated aneurysm suppression, and its efficacy in suppressing established experimental aneurysms, remain uncertain.
Metformin Prescription Associated with Reduced Abdominal Aortic Aneurysm Growth Rate and Reduced Chemokine Expression in a Swedish Cohort. [2021]Recent reports suggest that the negative association between diabetes mellitus and abdominal aortic aneurysm (AAA) may be driven by metformin, the world's most common antidiabetic drug rather than diabetes per se. We sought to investigate the association among AAA growth rate, chemokine profile, and metformin prescription in a contemporary Swedish cohort.
Association of Metformin and Abdominal Aortic Aneurysm Repair Outcomes. [2022]Metformin is a commonly used drug in diabetes mellitus treatment. Recently it has been suggested that the use of metformin on diabetes mellitus patients may lower the prevalence and slow the progression of AAA (abdominal aortic aneurysm) as well as the risk of rupture related mortality. The aim of this studywas to investigate the impact of metformin treatment on the risk of AAA repair related mortality and surgical complications.
Glucagon-Like Peptide-1 Receptor Agonists in Type 2 Diabetes Mellitus and Cardiovascular Disease: The Past, Present, and Future. [2022]Type 2 diabetes mellitus (T2DM) is associated with high cardiovascular morbidity and mortality, and cardiovascular diseases are the leading causes of death and disability in people with T2DM. Unfortunately, therapies strictly aimed at glycemic control have poorly contributed to a significant reduction in the risk of cardiovascular events. On the other hand, randomized controlled trials have shown that five glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and one exendin-based GLP-1 RA reduced atherosclerotic cardiovascular events in patients with diabetes at high cardiovascular risk. Furthermore, a meta-analysis including these six agents showed a reduction in major adverse cardiovascular events as well as all-cause mortality compared with placebo, regardless of structural homology. Evidence has also shown that some drugs in this class have beneficial effects on renal outcomes, such as preventing the onset of macroalbuminuria. In addition to lowering blood pressure, these drugs also favorably impacted on body weight in large randomized controlled trials as in real-world studies, a result considered a priority in T2DM management; these and other factors may justify the benefits of GLP-1 RAs upon the cardiovascular system, regardless of glycemic control. Finally, studies showed safety with a low risk of hypoglycemia and no increase in pancreatitis events. Given these benefits, GLP-1 RAs were preferentially endorsed in the guidelines of the European and American societies for patients with these conditions. This narrative review provides a current and comprehensive overview of GLP-1 RAs as cardiovascular and renal protective agents, far beyond their use as glucose-lowering drugs, supporting their effectiveness in treating patients with T2DM at high cardiovascular risk.
Janumet: a combination product suitable for use in patients with Type 2 diabetes. [2019]Inhibition of the enzyme dipeptidyl peptidase-4 represents the latest pharmacologic intervention to become available to assist patients with Type 2 diabetes to achieve glycemic control. A combination tablet of sitagliptin (Januvia) and metformin HCl (Glucophage) is now available from Merck (Janumet). The FDA has approved this drug for use in patients who are not adequately controlled by taking either sitagliptin or metformin HCl alone or for patients who are at present taking both simultaneously. Sitagliptin has been shown to be safe and effective at 100 mg daily doses. When given in combination with metformin the effect on glycemic control is thought to be complementary and possibly additive.
Glucagon-Like Peptide-1 Receptor Agonists and Cardiovascular Risk Reduction in Type 2 Diabetes Mellitus: Is It a Class Effect? [2019]Mimetics and analogs that extend the half-life of native glucagon-like peptide-1 (GLP-1), i.e., glucagon-like peptide-1 receptor agonists (GLP-1 RAs), at therapeutic doses, are indicated as adjuncts to diet and exercise, to improve glycemic control in adults with type 2 diabetes mellitus (T2DM). In patients with T2DM, GLP-1 RAs not only affect improvements in impaired beta cell and alpha cell function, suppress appetite, and induce weight loss but also possess multiple cardiovascular protective properties that potentially have a beneficial impact on atherosclerotic cardiovascular disease (ASCVD) morbidity and mortality.
Efficacy and Cardiovascular Safety of GLP-1 Receptor Analogues. [2021]Glucagon-like peptide- 1 receptor analogs (GLP-1RAs) are incretin mimetics with potent glucose-dependent insulinotropic action that translates to glycemic control in people with type- -2 diabetes mellitus (T2DM). These agents potentially have the ability to stimulate proliferation or prevent apoptosis of pancreatic Ξ²-cells, induce weight-loss and provide vascular benefits in patients with T2DM. Newer GLP-1RA, semaglutide has shown a robust reduction in HbA1c up to 1.5 - 1.8%. However, individual differences exist between the different GLP-1RAs, in terms of efficacy, pharmacokinetics, tolerability, and vascular protection. The potential of vascular protection offered by newer anti-diabetic agents has generated a lot of excitement in the field of diabetes, and to a large extent, is now driving treatment decisions. So far, six cardiovascular outcome trials of GLP-1 RAs have been published, analyzing lixisenatide (ELIXA), liraglutide (LEADER), semaglutide (SUSTAIN-6), long-acting exenatide (EXSCEL), dulaglutide (REWIND), and oral semaglutide (PIONEER 6) with a follow-up duration of 2-4 years. LEADER, REWIND and SUSTAIN-6 trials have demonstrated a reduction in rates of major adverse cardiovascular events with active GLP-1 RA treatment, but ELIXA, PIONEER 6 and EXSCEL, have been neutral. In this review, we discuss the available evidence from randomized controlled trials (RCTs) analyzing the cardiovascular effects of various GLP-1 RAs with the aim of comparing individual drugs. We have also summarized the general aspects of GLP-1RAs that can be applied in clinical practice.
Glibenclamide and metfoRmin versus stAndard care in gEstational diabeteS (GRACES): a feasibility open label randomised trial. [2021]Metformin is widely used to treat gestational diabetes (GDM), but many women remain hyperglycaemic and require additional therapy. We aimed to determine recruitment rate and participant throughput in a randomised trial of glibenclamide compared with standard therapy insulin (added to maximum tolerated metformin) for treatment of GDM.
Association Between Metformin and Abdominal Aortic Aneurysm: A Meta-Analysis. [2022]To systematically examine the association between metformin and abdominal aortic aneurysm (AAA) and provide a basis for the treatment of AAA.