Inclusion Criteria:
* Patients with newly diagnosed histologically confirmed GBM (WHO grade IV, IDH wild type) undergoing surgical resection;
* hypomethylation or hypermethylation of MGMT assessed post-surgery;
* adult patients (≥18 years), both sexes;
* Patients undergoing Stupp protocol including patients aged \> 70 years performing the hypofractionated protocol and three weeks of chemotherapy;
* Karnofsky Performance Status (KPS)\> 60 assessed post-surgery;
* life expectancy at least 6 months defined by size and location of lesion tumor;
* freely given written informed consent prior to any activity related to the study. Patients must be able to communicate with the investigator and comply with the study procedures;
* Women of childbearing age must test negative for pregnancy at enrollment and, if they have sexual intercourse, they must agree to use specific contraceptive methods. Female subjects of childbearing age, i.e., fertile, after menarche and until post-menopause unless they are permanently infertile, who are sexually active, must apply a highly effective method of birth control with a low failure rate (i.e., less than 1 percent per year), such as combined hormonal contraception (containing estrogen and progestin) combined with ovulation inhibition (oral intravaginal, or transdermal), progestin-only hormonal contraception associated with ovulation inhibition (oral, injectable, or implantable), intrauterine device (IUD), intrauterine hormone delivery system (IUS), bilateral tubal occlusion, vasectomized partner, or sexual abstinence, throughout the treatment period and for four weeks after the last dose of the study treatment. Hormonal methods other than levonorgestrel-containing devices or medroxyprogesterone injections should be supplemented with the use of a male condom. Women of nonfertile age may be included if surgically sterile or postmenopausal for at least 2 years. The investigator is responsible for determining whether the patient has adopted an appropriate method of contraception for participation in the study.
* Male subjects with female partners of childbearing age must use condoms during treatment and until the end of relevant systemic exposure.
Exclusion Criteria:
* Multicenter GBMs;
* Patients diagnosed with diabetes or diabetes-related conditions;
* other active malignancies;
* hypersensitivity, intolerance to metformin or excipients;
* Impaired renal function with creatinine clearance \< 60 mL/min assessed at recruitment, liver failure assessed at recruitment by clinical history and examination of ALT, AST and total bilirubin, and other contraindications to metformin use;
* taking metformin, insulin or other biguanides, regardless of the reason;
* pregnancy or lactation;
* patient has serious pre-existing medical conditions that, in the opinion of the investigator, would preclude participation in this study.
