Relationship Between Metformin Therapy and Risk of Colorectal Cancer in Patients with Diabetes Mellitus: a Meta-analysis

Objective: At present, there are many studies on metformin and the risk of colorectal cancer in patients with diabetes, but the conclusions are contradictory. Our aim is to comprehensively collect the published literature and systematically evaluate the relationship between metformin and the risk of colorectal cancer in patients with diabetes.

Methods: We systematically searched the MEDLINE, EMBASE, and CENTRAL databases up to March 2020. We adopted adjusted estimates and their 95% confidence intervals (CI) to calculate summary effect estimates using either a fixed-effects or a random-effects model.

Results: A total of 17 articles were included in this study, with a total of 1,092,074 patients with diabetes. Meta-analysis of observational studies showed that metformin treatment could significantly reduce the incidence of colorectal cancer in diabetic patients (adjusted RR = 0.884, 95%CI = 0.829-0.943), and there was heterogeneity between studies (p = 0.013, I = 47.9%). Subgroup analysis showed that metformin treatment was significantly associated with a significantly reduced risk of colorectal cancer in diabetics in America and Europe (adjusted RR = 0.852, 95%CI = 0.786-0.924; adjusted RR = 0.900, 95%CI = 0.845-0.958). Patients with diabetes treated with metformin had a significantly lower risk of colorectal cancer compared with patients who had never been treated with metformin or sulfonamide monotherapy (adjusted RR = 0.863, 95%CI = 0.776-0.960; adjusted RR = 0.911, 95%CI = 0.882-0.941).

Conclusions: Metformin therapy is associated with a significantly reduced risk of colorectal disease in patients with diabetes, and it is necessary to conduct larger, more standardized clinical studies to verify this conclusion.