Cancer Chemoprevention by Metformin Hydrochloride Compared to Placebo in Oral Potentially Malignant Lesions

Inclusion Criteria: * Both genders with age range from 20 to 70 years. * Patients able to return for the follow up visits and can perform oral hygiene measures. * Clinically diagnosed and histologically confirmed as having oral potentially malignant lesions. * Patients agreed to sign a written consent after understanding the nature of the study * Patients have diagnosed oral premalignant lesion/lesions and not yet turned into malignancy (atrophic lichen planus- leukoplakia-erythroplakia - oral submucous fibrosis) Exclusion Criteria: * \- Diabetic patients (Diabetes Mellitus Type I \& II) * Patients have cardiovascular, lung, Renal, Liver diseases * Patients on H2 blocker \& proton pump inhibitors therapy as Ranitidine (affects metformin absorption and clearance) * Those with allergy or sensitivity to Metformin or Retinoids therapy or having any contraindication for their use. * Systemic and/or local systemic drug therapy within the last 3 months prior to the start of the study * Patients on steroidal or Non-steroidal anti-inflammatory drugs (NSAIDs) for at least the last 6 months * Patients on Antibiotics treatment for at least the last 2 months * Patients on Retinoid, green tea supplements or another natural products therapy * Patients with already diagnosed malignant lesion/lesions * Pregnant or Lactating females * Vulnerable groups as prisoners, mentally disabled, etc…