Investigating Senolytic Properties in Pulmonary Rehabilitation and Metformin in COPD Exacerbations

The purpose of this study is to investigate the safety and tolerability of Metformin and how it changes blood markers associated with aging in persons who have chronic obstructive pulmonary disease (COPD) who do not have diabetes.

Inclusion Criteria: * 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 Exclusion Criteria: * Diabetes or actively being treated with metformin * 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 * 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 * Cognitive impairment * Dementia * Heart failure with reduced ejection fraction \< 50% * Alcohol use disorder * Disability preventing in-person visits * 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