Limiting AAA With Metformin (LIMIT) Trial

Inclusion criteria

• Provision of signed and dated informed consent;
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female, aged 50 to 95 years inclusive;
• Have a maximal orthogonal infrarenal aortic diameter between 35 and \< 50 mm for males and between 30 and \< 45 mm for females as measured by CTA;
• Eligible participants must have an estimated glomerular filtration rate (eGFR) of ≥ 30 ml/min/1.73 m2 at the initiation of trial participation, and must remain ≥ 30 ml/min/1.73 m2 throughout the term of the study to continue participation;
• HgbA1c must be ≤ 6.5% at initiation to receive study medication;
• Ability to take oral medication and be willing to adhere to the medication regimen throughout the course of the trial;
• Must be willing and able to undergo two computed tomographic aortograms (CTA, with timed intravenous iodinated contrast injections if possible) at initiation and termination of study participation;
• 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. 7.3

Exclusion criteria

• Diagnosis of, or taking medications for, diabetes mellitus, as defined as HgbA1c \> 6.5% at baseline evaluation; 2. Known hypersensitivity to metformin hydrochloride. Individuals with known prior anaphylactic reaction to iodinated contrast will have the option of CT scan without contrast or will not be eligible to participate. Individuals with a prior allergic reaction not including anaphylaxis will be managed with the standard CT protocol for premedication for allergy to contrast - 3 doses of prednisone (50 mg p.o. per) beginning 13 hours prior to the procedure as well as 50 mg of Benadryl p.o. Premedication start times are as follows: 13 hours before contrast, 50 mg PO prednisone 7 hours before contrast, 50 mg PO prednisone 1 hour before contrast, 50 mg PO prednisone + 50 mg PO diphenhydramine These individuals will also be given the option of CT scan without contrast if unwilling to follow the premedication as indicated above; 3. Presence of metabolic acidosis, defined as total CO2 below the lower limit of normal on chemistry panel obtained during determination of study eligibility; 4. Expected survival less than two years; 5. Prior surgical AAA repair, or anticipated repair within two years; 6. Known thoracic aortic aneurysm disease, as defined as a prior dissection or thoracic aortic diameter \> 5 cm); 7. The presence of known syndromic aortic conditions, including but not limited to Ehlers Danlos or Marfan Syndromes, or the at-risk allele in the ACTA2 gene mutation or similar conditions; 8. Severe liver disease, jaundice, or active hepatitis; 9. Severe anemia, defined as a Hgb \< 10g/dl; 10. Concurrent participation in other investigational drug trials; 11. For female participants of childbearing potential: pregnancy, intent to become pregnant, lactation, or unwilling or unable to use an effective method of contraception; 12. Alcoholism or chronic excessive alcohol intake; 13. Common iliac artery aneurysms \> 3.5 cm; 14. Uncontrolled hypertension defined as Systolic BP≥200, or considered to have hypertensive emergency or urgency.