Metformin Hydrochloride in Preventing Oral Cancer in Patients With an Oral Premalignant Lesion

Inclusion Criteria: * Participants with oral leukoplakia or erythroplakia with mild, moderate, or severe histologic dysplasia, or hyperplasia not associated with mechanical factors such as ill-fitted dentures * Measurable disease - minimum lesion size of 8 x 3 mm before initial biopsy * Karnofsky performance status \>= 70% * Leukocytes \>= 3,000/microliter * Absolute neutrophil count \>= 1,000/microliter * Platelets \>= 100,000/microliter * Total bilirubin =\< 1.5 × institutional upper limit of normal (ULN) * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\<1.5 × institutional ULN * eGFR \> 40 mL/min using the Cockcroft-Gault equation * Life expectancy \> 3 months * Willing to use adequate contraception (barrier method, abstinence, subject has had a vasectomy or partner is using effective birth control or is postmenopausal) for the duration of study participation * Ability to take oral medication * Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: * Patients with diabetes who are taking insulin or oral agents * History of diabetic ketoacidosis * Participants may not be receiving any other investigational agents within past 3 months * History of allergic reactions attributed to compounds of similar chemical composition to metformin or prior use of metformin within the last year * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, human immunodeficiency virus (HIV)-positive, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements * Oral carcinoma in situ * History of chronic alcohol use or abuse defined as any one of the following: a) average consumption of 3 or more alcohol containing beverages daily in the past 12 months; b) consumption of 7 or more alcoholic beverages within a 24 hour (hr) period in the past 12 months * Glycated hemoglobin (HbA1c) \> 8% * Pregnancy or nursing women * Acute or chronic liver disease, evidence of hepatitis (infectious or autoimmune), cirrhosis or portal hypertension * History of renal disease * History of prior head and neck squamous cell carcinoma (HNSCC) unless curatively treated for \>= 1 year * Have received chemotherapy and/or radiation for any malignancy (excluding non-melanoma skin cancer and cancers confined to organs with removal as only treatment) in the past 2 years; ongoing adjuvant hormonal therapy for breast cancer is allowed