Role of Metformin in the Treatment of Cholangiocarcinoma: A Systematic Review.

e16132 Background: Non-cancer medications and their potential anti-cancer activity have attracted significant interest in recent years. The aim of this research is to conduct a systematic assessment of the existing evidence on the usefulness of metformin in the treatment of cholangiocarcinoma. Methods: We conducted literature search using PubMed, Clinicaltrials.gov, Embase, and Cochrane to retrieve studies evaluating the role of Metformin in the treatment of Cholangiocarcinoma. Three studies were finalized after careful screening. Results: We analyzed 3 studies. The total population was 638. The types of Cholangiocarcinoma varied from intrahepatic cholangiocarcinoma found in 293, to extrahepatic Cholangiocarcinoma in 365 and gallbladder carcinoma in 149 patients. Patients were in different stages of treatment such as undergoing chemotherapy, surgery or post- resection and/or post chemotherapy. The mean survival rate was significantly increased to 30.4 months and 13.2 months in patients using Metformin vs. 23.48 months and 10.3 months among patients not using Metformin (p < 0.0005) after resection of the tumor. An increase in the mean survival rate was reported among patients using Metformin vs. non-users after the administration of chemotherapy, i.e., 25.9 months vs. 10.6 months (p = 0.0016), respectively. Metformin in combination with Chloroquine showed favorable results regarding adverse events, however, no clinical activity was reported against IDH-1 mutated intrahepatic cholangiocarcinoma. Conclusions: Our analysis concludes while the use of Metformin is associated with significantly improved post-operative survival, it does not show any significant clinical activity against IDH-1 mutated intrahepatic cholangiocarcinoma. Metformin also showed significant improvement in patients taking chemotherapy. Studies, including trials to evaluate the effectiveness of Metformin alone or used in combination with non-cancer medications or chemotherapeutic agents could provide more definitive recommendations for the treatment of Cholangiocarcinoma.[Table: see text]