There is no consensus on treatment of leukoplakia but surgical excision is the preferred choice if suitable in size, which does not prevent clinical recurrence and malignant transformation. Chemoprevention is a new direction in the management of OL using various topical and systemic agents such as; vitamin A, lycopene, celecoxib, green tea extract, and metformin.

While metformin cannot realistically be used as cancer mono-therapy, it can be used as an adjunct and can have a more promising effect on lesions that have yet to undergo malignant transformation. Thus, the aim of this study is to investigate the efficacy of combined chemo-preventive effect of topical and systemic Metformin on oral leukoplakia.

Inclusion Criteria:

• Adult patients over 21 years.
• Patients clinically diagnosed and histologically confirmed as having oral Leukoplakia.
• Lesions with mild to moderate degree of dysplasia.
• Patients who agree to sign a written consent after understanding the nature of the study.

Exclusion Criteria:

• Patients with lesions showing sever degree of dysplasia.
• Patients who have cardiovascular, lung, Renal, Liver diseases
• Patients on metformin therapy (eg: Diabetes Mellitus, PCOS, …etc.)
• Patients on H2 blocker & proton pump inhibitors therapy as Ranitidine (affects metformin absorption and clearance)
• Those with allergy or sensitivity to Metformin therapy or having any contraindication for their use.
• Patients on Retinoid, green tea supplements or another natural products therapy
• Patients with other accompanying oral lesions
• Pregnant or Lactating females