Metformin, Cancer, Alphabet Soup, and the Role of Epidemiology in Etiologic Research

Libby et al. (1), in this issue of Diabetes Care, report a lower incidence of a broad range of cancers among diabetic patients treated with metformin. Specifically, by linking data from a population-based diabetes registry with those from a drug use registry and a cancer registry, they effectively followed medication use in over 8,000 diabetic individuals and ascertained over 700 incident cancers. They found, over a 10-year period, that metformin use was associated with a 54% (95% CI 47–60) lower crude and a 37% (25–47) lower adjusted incidence of cancer. From the survival analysis they performed adjusting for age, sex, BMI, smoking status, and a social deprivation index, one can estimate the association in absolute terms: considering the cancer rate of 11.6% for non–metformin users, for every 23 patients receiving metformin in this cohort one fewer developed cancer (number needed to treat = 1/[0.37 × 0.116]). Their findings are internally consistent. In patients with the longest history of metformin use prior to cancer onset, incidence tended to be lowest. Metformin users who developed cancer also had a greater survival postdiagnosis. A protective association of similar degree was documented against lung, bowel, and breast cancer.

Because these findings come from a large cohort study constructed with record linkage rather than from a randomized clinical trial, they require trial confirmation prior to clinical application. Nevertheless, they add to a rapidly growing literature suggesting, on the basis of a plausible mechanism and consistent empirical findings in both laboratory animals and humans, that metformin not only exerts a major protective effect against the development of a wide range of cancers but also improves prognosis in those found to have these cancers.

In addition to a preliminary report based on the same diabetes registry (2), the findings of three other studies are in consonance …