Clinical Trials

Inclusion Criteria:

1. IPF diagnosis by enrolling investigator (following the 2022 updated guidelines on diagnosis and management of IPF)
2. Age 40 years or older
3. HbA1c \< 9% at screening
4. High risk by proteomic signature (proteomic signature present) for participants randomized only (for participants randomized only; participants that are proteomic signature absent will undergo remote study assessments at 12 and 24 months only).
5. If on FDA-approved treatment(s) for IPF, on a stable dose for at least 8 weeks prior to randomization
6. Ability to provide informed consent

Exclusion Criteria:

1. Taking metformin within 3 months of randomization
2. Allergy or intolerance to metformin
3. Use of insulin or insulin secretagogue(s) at randomization
4. Pregnancy, planning to become pregnant, or lactating
5. Women of childbearing potential not willing to remain abstinent (refrain from heterosexual intercourse) or use two adequate methods of contraception, including at least one method with a failure rate of \<1% per year during study participation
6. History of biochemically-confirmed acidosis (lactate \> 5.0 mmol/L)
7. Estimated glomerular filtration rate less than 45 mL/min/1.73 m2 at screening
8. Moderate-to-severe liver disease, decompensated heart failure, or any other condition that may make the participant unsuitable for inclusion as assessed by the study investigator at each site
9. Receipt of an investigational study agent as part of a therapeutic trial within 30 days of the Screening Visit (Visit 0)
10. Continuous supplemental oxygen use at rest greater than 2 L/min
11. Unable to swallow pills
12. Taking a medication that has a major interaction with metformin, including acetazolamide (Diamox), cimetidine (Tagamet), dolutegravir, gatifloxacin, levoketoconazole, ranolazine, or carbonic anhydrase inhibitors. Occasional use of carbonic anhydrase inhibitors for travel is permitted.
13. Current alcohol intake ≥ 15 drinks per week in men, ≥ 8 drinks per week in women or ≥ 5 drinks per occasion in men, ≥ 4 drinks per occasion in women
14. Listed for transplant at the time of randomization