Metformin to Attenuate Progressive Respiratory Decline in Idiopathic Pulmonary Fibrosis

Prior treatment

• 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.
• Listed for transplant at the time of randomization

Other illness

• Allergy or intolerance to metformin
• 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
• 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

Lab values

• History of biochemically-confirmed acidosis (lactate \> 5.0 mmol/L)

Other

• Taking metformin within 3 months of randomization
• Use of insulin or insulin secretagogue(s) at randomization
• Pregnancy, planning to become pregnant, or lactating
• Estimated glomerular filtration rate less than 45 mL/min/1.73 m2 at screening
• Receipt of an investigational study agent as part of a therapeutic trial within 30 days of the Screening Visit (Visit 0)
• Continuous supplemental oxygen use at rest greater than 2 L/min
• Unable to swallow pills
• 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

• IPF diagnosis by enrolling investigator (following the 2022 updated guidelines on diagnosis and management of IPF)
• Age 40 years or older
• HbA1c \< 9% at screening
• 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).
• If on FDA-approved treatment(s) for IPF, on a stable dose for at least 8 weeks prior to randomization
• Ability to provide informed consent