Compared with sulfonylureas like glipizide and glyburide, the antidiabetic agent metformin may not significantly reduce the short-term risk of breast cancer in postmenopausal women aged 65 years or older, a study published in Epidemiology has shown.1

Numerous observational studies have demonstrated a potential chemopreventive benefit of metformin on breast cancer in patients with diabetes; however, these studies were limited by their various time-related biases. Therefore, researchers designed an observational study that would eliminate such biases to compare the effect of metformin with that of sulfonylureas on breast cancer risk.

Investigators analyzed US Medicare claims data from 45,900 women aged 65 years or older who initiated monotherapy with metformin and 13,904 who received sulfonylureas. All patients were free of cancer and renal disease in the 6 months prior to initiating antidiabetic therapy and had enrolled in Medicare between 2007 and 2012. Follow-up for the metformin group was 58,835 person-years and 16366 person-years for the sulfonylurea group.

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Results showed that 385 patients who initiated metformin and 95 of those treated with a sulfonylurea were diagnosed with breast cancer during follow-up. A propensity-score analysis weighted to minimize any measured baseline differences between treatment groups demonstrated a breast cancer incidence rate of 5.8% (95% CI, 4.7-7.1) and 5.5% (95% CI, 4.9-6.2) in the metformin and sulfonylurea groups, respectively.

After adjusting for confounding factors, investigators found no significant difference in the risk of breast cancer between metformin and sulfonylurea initiators (hazard ratio, 1.2; 95% CI, 0.94-1.6).

The study further demonstrated that controlling for unmeasured confounding by body mass index and smoking had no effect on the estimates of breast cancer risk.

Although this study is limited by its short follow-up time and lack of breast cancer subtype data, the findings suggest that older women initiating metformin did not have a reduced risk for developing breast cancer compared with women initiating an alternative antihyperglycemic agent.

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Randomized clinical trials have been initiated to assess the affect of metformin on breast cancer risk and will provide further insight into metformin’s role in the prevention of breast cancer.


  1. Hong JL, Funk MJ, Buse J, et al. Comparative effect of initiating metformin versus sulfonylureas on breast cancer risk in older women. Epidemiology. 2017 Feb 3. doi: 10.1097/EDE.0000000000000635 [Epub ahead of print]