Metformin increases cancer specific survival in colorectal cancer patients-National cohort study

Purpose: We aimed to assess oncological outcomes in colorectal cancer patients with type 2 diabetes mellitus (T2DM) using metformin. Methods: Patients with colorectal cancer and T2DM during 2000-2012 period were identified form Lithuanian Cancer Registry and the National Health Insurance Fund database. Colorectal cancer-specific survival (CS) was the primary outcome. It was measured from date of colorectal cancer diagnosis to date of death due to colorectal cancer, or last known date alive. Results: 15,052 people who ma eligibility criteria for this analysis, including 1094 (7.27%) with pre-existing type 2 diabetes (271 metformin never users and 823 metformin users) and 13 958 people without diabetes assessed. During follow-up (mean follow-up time was 4.4 years, with range from 1 day to 17 years) there were 10,927 deaths including 8559 from colorectal cancer. Significantly lower risk in CS between diabetic and non-diabetic people with lower risk of cancer-specific mortality (HR 0.87, 95% CI 0.80-0.94) in diabetic patient population was seen. After adjustment for age, stage a diagnosis and metformin usage, significant difference in colorectal CS between metformin users in diabetic patient population compared to non-diabetics and metformin non-users in diabetic patient population was found (0.80 (0.72-0.89) vs 1.00 and vs 1.05 (0.91-1.23)). Overall survival (OS) was better for diabetic patients with significant difference in diabetic metformin users (HR 0.91, 95% CI 0.79-0.94). Conclusions: Colorectal cancer patients with T2DM treated with metformin as part of their diabetic therapy appear to have a superior OS and CS. However, prospective controlled studies are still needed to evaluate the efficacy of metformin as an anti-tumor agent.