Metformin Intake Suppresses the Degree of Liver Metastasis From Colorectal Cancer in Diabetic Patients but Does not Improve their Prognosis

Author(s): Akira Saito, Joji Kitayama, Hisanaga Horie, Koji Koinuma, Hideyuki Ohzawa, Hironori Yamaguchi, Hiroshi Kawahira, Toshiki Mimura, Alan Kawarai Lefor, Naohiro Sata

Background
Metformin reduces the risk of, and mortality from, colorectal cancer in patients with diabetes mellitus. However, the effect of metformin on patients with stage IV disease is unknown. In the present study we reviewed the clinical features and outcomes of patients with diabetes mellitus and stage IV colorectal cancer (M1, liver metastases) treated with or without metformin.

Methods
The 202 patients with colorectal cancer and macroscopic liver metastasis who were treated in the Department of Surgery or Department of Clinical Oncology at Jichi Medical University Hospital from January 2006 through June 2019 were surveyed treatment of diabetes, clinical and pathological factor and prognosis of these patients.

Results
We retrospectively examined the effect of metformin use on outcomes in 32 patients with liver metastases from colorectal cancer. Hepatic metastases were stage H1 in 8/8 patients taking metformin and stage H2-3 in 17/24 non-users. Of 22 patients who underwent colectomy, colorectal tumors were pT4 in 5 metformin users, and pT2-3 in 10/17 non-users. The mean survival of metformin users and non-users was equal (28.0 mo vs 29.3 mo, p>0.05). No significant difference was detected when survival was compared between 6 metformin users and 19 non-users who received systemic chemotherapy.

Conclusion
These results suggest that metformin has less potent anti-tumor effects in patients with advanced stage disease. Metformin for the treatment of patients with metastatic colorectal cancer requires further study.