Inclusion Criteria:
1. Patients must have histologically confirmed high-grade glioma (e.g. glioblastoma, gliosarcoma, anaplastic astrocytoma, anaplastic oligodendroglioma, anaplastic mixed glioma or other anaplastic gliomas).
2. Patients must have an MRI performed within 21 days prior to beginning the study diet and on a fixed dose of steroids for at least 5 days. If the steroid dose is increased between the date of imaging and registration, a new baseline MR/CT is required.
3. Patients must not have been exposed to bevacizumab.
4. Patients cannot be taking insulin or other oral hypoglycemic. Must be at least 6 weeks from last oral hypoglycemic or insulin.
5. Must not have known type 1 or type 2 diabetes and expected to need either insulin and/or an oral hypoglycemic agents within the next 6 months.
6. Patients must be \>18 years old.
7. Karnofsky performance status \>60%.
8. Life expectancy of greater than 12 weeks.
9. Patients must have normal organ and marrow function as defined below:
* Leukocytes \>3,000/mcL
* Absolute neutrophil count \>1,000/mcL
* Platelets \>100,000/mcL
* Total bilirubin \<2.0 X institutional upper limit of normal (unless known to have Gilbert's Disease)
* AST (SGOT)/ALT(SGPT) \<2.5 X institutional upper limit of normal
* Serum Glucose: \< 200 mg/dL
* Creatinine \< 1.5 mg/dL (for males), \< 1.4 mg/dL (for females), or within normal lab limits OR
* Creatinine clearance \>60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
10. Patients must not have any significant medical illnesses that, in the investigator's opinion, cannot be adequately controlled with appropriate therapy or would compromise the patients' ability to tolerate this therapy
11. Patients having undergone recent resection or progressive tumor will be eligible as long as all of the following conditions apply:
1. They have recovered from the effects of surgery.
2. On a steroid dosage that has been stable for at least 5 days.
3. Residual disease following resection of recurrent tumor is not mandated for eligibility into the study. To best assess the extent of residual disease postoperatively, a MRI should be done:
* No later than 96 hours in the immediate post-operative period or
* At least 4 weeks post-operatively, and
* Within 14 days of registration, and
* If the 96-hour scan is more than 21 days before registration, the scan needs to be repeated. If the steroid dose is increased between the date of imaging and registration, a new baseline MRI is required on a stable steroid dosage for at least 5 days.
12. Patients must have the ability to understand and the willingness to sign a written informed consent document.
Exclusion Criteria:
1. Patients who are receiving any other investigational agents.
2. Patients who have had prior therapy with bevacizumab and/or other VEGF inhibitors.
3. Patients who are taking insulin or other oral hypoglycemic. Must be at least 6 weeks from last oral hypoglycemic or insulin.
4. History of allergic reactions attributed to metformin.
5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, diabetes requiring oral hypoglycemic drugs and/or insulin, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
6. Patients known to have a malignancy that has required treatment in the last 12 months and/or is expected to require treatment in the next 12 months (except nonmelanoma skin cancer or carcinoma in-situ in the cervix).
7. The effects of a Ketogenic diet or metformin on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.
8. Patients with current alcoholism.
