Diabetes therapy and cancer risk: causal effects and other plausible explanations

Four reports in Diabetologia presented data on the association between hypoglycaemic agents and the risk of cancer. One study showed a higher risk of cancer overall in subjects with diabetes receiving insulin or sulfonylureas than in those on metformin. In another study, the risk of cancer overall increased with dose for any type of insulin and, among high doses, insulin glargine (A21Gly,B31Arg,B32Arg human insulin)-only users had a higher risk than subjects on human insulin. In two studies, users of insulin glargine alone had a higher risk of breast cancer than those on other insulins, a third study found no association. Whether these associations are causal or at least partially explained by chance or biases such as confounding, reverse causation, selection or detection biases is arguable. Current epidemiological evidence is insufficient to confirm a carcinogenic effect of specific insulins on specific cancers. However, the potential dose effect of insulin overall, and insulin glargine in particular, on colon and breast cancer deserves further attention.