Metformin Trims Colorectal Cancer Risk in Diabetes

The drug metformin appears to reduce the risk of colorectal cancer (CRC) in patients with diabetes mellitus (DM), according to a new study that, for the first time, assessed the effects of the drug on younger patients with DM in the United States.

Patients with type 2 DM may be at increased risk for CRC resulting from hyperinsulinemia, hyperglycemia, and chronic inflammation. “Emerging evidence from observational studies has suggested that metformin may be beneficial in the primary prevention of CRC,” stated the researchers, led by Amikar Sehdev, MD, MPH, a medical oncologist at the University of Chicago.

Metformin, a biguanide, exerts its antihyperglycemic effects by decreasing hepatic glucose production, decreasing intestinal absorption of glucose, and improving insulin sensitivity by increasing peripheral glucose uptake and utilization.

Because environmental factors such as Western diet and obesity are implicated in CRC, the researchers conducted a large case-control study of more than 8000 patients with DM to assess the effects of metformin on the incidence of CRC in a US population.

They identified patients with DM and CRC from MarketScan databases. Each case was matched for age, sex, and geographical region with up to 2 controls. The researchers analyzed 2682 patients with DM and newly diagnosed CRC, mean age 57 years, and 5364 cancer-free patients with DM, mean age 55 years, which is younger than the average age at CRC diagnosis.

In each group, about 60% of participants were male and 40% were female. The researchers used prescription tracking within the 12-month period before the index date to assess metformin exposure.

In a multivariable analysis model, they found that any metformin use correlated with a 15% reduction in the odds of developing CRC. The beneficial effect of metformin use was reduced to 12% after adjustment for health care use. There was no significant association with metformin dose, duration, or total exposure in dose-response analyses.

“Metformin use appears to be associated with a reduced risk of developing CRC among diabetic patients in the United States,” the researchers concluded.

A dose-related effect would have added strength to the findings, the researchers stated. They suggested the lack of a dose-response effect may be the result of a threshold effect at the lowest dose, which was less than 1000 mg/d.

The researchers suggested that metformin might reduce the risk of CRC by lowering the blood glucose levels that cancer cells rely on for energy and by increasing the cellular response of the AMP-activated protein kinase pathway, which would ultimately block protein synthesis and reduce the growth and rapid reproduction of cancer cells.

Previously, observational studies have shown that metformin reduces the incidence of CRC by 27% to 44%. Also, large meta-analyses have shown the drug reduces the risk by more than one-third.

The researchers noted that their findings were based on a younger and healthier patient population, which could have resulted in an underdiagnosis of CRC.

The researchers published their results in the April 1, 2015, issue of Cancer.