Investigating Senolytic Properties in Pulmonary Rehabilitation and Metformin in COPD Exacerbations

Prior treatment

• Diabetes or actively being treated with metformin
• Persons with an unstable medical condition (including but not limited to unstable angina, acute heart failure exacerbation, acute neurological symptoms) or COPD exacerbation within 30 days prior to enrollment will be excluded
• Active treatment with Carbonic Anhydrase Inhibitors including but not limited to topiramate, zonisamide, acetazolamide, diclofenamide

Other illness

• Metformin allergy
• History of lactic acidosis not explained by acute, severe illness
• History of low vitamin B12 levels and unwilling to begin standard of care treatment for low vitamin B12 levels
• Cognitive impairment
• Dementia
• Alcohol use disorder

Lab values

• Hepatic impairment defined as history of cirrhosis or abnormal liver function tests (e.g., alanine transaminase (ALT): 7-55 units per liter (U/L), aspartate transaminase (AST): 8-48 U/L, alkaline phosphatase (ALP): 40-129 U/L, or bilirubin: 0.1-1.2 milligrams per deciliter (mg/dL))
• Renal impairment defined as eGFR \< 60 mL/min/1.73m2
• Heart failure with reduced ejection fraction \< 50%

Other

• Disability preventing in-person visits

• Age 65 and older
• History of COPD defined by spirometry demonstrating FEV1/FVC \< 70%
• 10 or more tobacco pack year history
• History of frequent exacerbations defined as: 1 severe (i.e., COPD hospitalization) or 2 moderate (i.e., outpatient treated exacerbations) in the previous 12 months