Metformin With Neoadjuvant Chemoradiation to Improve Pathologic Responses in Rectal Cancer

Inclusion Criteria: 1. Plan for care inclusive of: i. standard of care neoadjuvant chemoradiation ii. planned total mesorectal excision (TME) 2. Histologically confirmed adenocarcinoma of the rectum 3. At least one of the following: i. T3 or T4 lesions ii. T2 lesions ≤ 1 mm to the mesorectal fascia iii. Node positive rectal tumor 4. ECOG performance status of 0 or 1 5. Provide written informed consent 6. Female participants of childbearing potential agree to use adequate methods of contraception from the start of metformin administration until the start of CRT. Contraception will not be required to be continued during or after CRT as this treatment renders participants infertile. Clinically acceptable methods of birth control for this study include intrauterine devices (IUD), birth control pills, hormonal implants, injectable contraceptives, and using barrier methods such as condoms, vaginal diaphragm with spermicide, or sponge. Exclusion Criteria: 1. Diagnosis of diabetes 2. Current use of metformin 3. Prior pelvic radiation 4. Life expectancy \< 6 months. 5. Active infection 6. Creatinine \> 1.5X ULN, within 1 month prior to baseline 7. AST, ALT \> 2.5X ULN, within 1 month prior to baseline 8. Bilirubin \> 1.5 ULN, within 1 month prior to baseline 9. Pregnant or breastfeeding women