Neuroendocrine tumors are rare but recent data showed a relevant increase in its incidence. The Mammalian Target of Rapamycin (mTOR), one of most important area of research, has demonstrated be a therapeutic target in these tumors. The metformin has demonstrate in preclinical studies having an antineoplastic action by inhibiting the mTOR pathway, and may be an alternative treatment for this disease.

Eligible patients for this study should have metastatic gastroenteropancreatic neuroendocrine tumors well differentiated (grade 1 or grade 2) and will be treated with metformin 850 mg every 12 hours, and each cycle will consist of 30 days. After 180 days of treatment the efficacy of metformin under the control of disease progression will be evaluated. As a secondary outcome the investigator will check the patient adherence to the treatment, the control of patient symptoms with functioning neuroendocrine tumor, and disease free survival. Also will be performed an analysis of immunohistochemical expression of mTOR pathway proteins of these patients.

Inclusion Criteria:

• Metastatic well-differentiated neuroendocrine tumor grade 1 or 2 with histological confirmation;
• Performance status according to Eastern Cooperative Oncology Group (ECOG) 0 to 2;
• Able to take pills;
• Age ≥ 16 years;
• Ability to Provide Written Informed Consent;
• Adequate organ function;

Exclusion Criteria:

• Patient with out of control severe hormonal syndrome;
• Diabetic patients under metformin treatment, or those who have received treatment with metformin within 3 months;
• Patient with hypersensitivity to biguanides, kidney or liver failure, or other conditions that predispose to lactic acidosis;
• History of severe clinical or psychiatric illness, that would prevent participation in the study by clinical judgment;
• Patients who participate in other protocol with experimental drugs;
• Patients under any kind of active infection;
• Patients who have received chemotherapy within 3 weeks;
• Patients pregnant or lactating;
• Diabetic patients who require higher dose of metformin 850mg x 2 daily;