In a study published this month in the journal Cancer Causes & Control, Harvey J. Murff, MD, MPH, and colleagues found that patients taking metformin had a reduced rate of liver cancer compared to patients taking an alternative anti-diabetes drug.

Several observational studies suggest that metformin reduces the incidence of cancer risk; however, many of these studies suffer from time-related biases and several cancer outcomes have not been investigated due to small sample sizes.

While other previous studies have found associations between metformin and decreased risk of several cancer types, most of them have been impacted by biases related to differences in treatment time between cases and controls, as well as confounding factors such as body mass index and glycemic control.

The authors carefully controlled for these factors in a study of patients with diabetes included in national Veterans Health Administration databases. They found no association between metformin use and the incidence of 10 solid tumor types—other than liver cancer. Their work suggests that metformin should be further studied clinically for the prevention of liver cancer.

Association between metformin use and risk of cancer

The authors constructed a propensity score-matched retrospective cohort of 84,434 veterans newly prescribed metformin or a sulfonylurea as monotherapy. They used Cox proportional hazard regression to assess the association between metformin use compared to sulfonylurea use and incidence cancer risk for 10 solid tumors.

They adjusted for clinical covariates including hemoglobin A1C, antihypertensive and lipid-lowering medications, and body mass index. Incidence cancers were defined by ICD-9-CM codes.

Among 42,217 new metformin users and 42,217 matched-new sulfonylurea users, they identified 2,575 incidence cancers. Metformin was inversely associated with liver cancer (adjusted hazard ratio [aHR] = 0.44, 95% CI 0.31, 0.64) compared to sulfonylurea.

They found no association between metformin use and risk of incidence bladder, breast, colorectal, esophageal, gastric, lung, pancreatic, prostate, or renal cancer when compared to sulfonylurea use.

In this large cohort study that accounted for time-related biases, they observed no association between the use of metformin and most cancers; however, they found a strong inverse association between metformin and liver cancer. Randomized trials of metformin for prevention of liver cancer would be useful to verify these observations.