Insulin Therapy and Cancer in Type 2 Diabetes

Abstract

Despite the availability of many other agents, insulin is widely used as a treatment for type 2 diabetes. In vitro, insulin stimulates the growth of cancer cells, through the interaction with insulin-like growth factor-1 (IGF-1) receptors and its own receptors. In observational surveys on type 2 diabetes, insulin therapy is associated with an increased incidence of several forms of cancer, although it is difficult to discriminate the effect of confounders from that of insulin itself. Randomized trials do not confirm the increased risk associated with insulin therapy, although they do not allow to rule out some negative effects on specific forms of cancer, at least at higher doses. Among insulin analogues, glargine has a higher affinity for the IGF-1 receptor and a greater mitogenic potency in vitro than human insulin, but it is extensively metabolized in vitro to products with low IGF-1 receptor affinity. Overall, epidemiological studies suggest a possible increase of risk with glargine, with respect to human insulin, only at high doses and for some forms of cancer (i.e., breast). Data from clinical trials do not confirm, but are still insufficient to totally exclude, such increased risk. However, beneficial effects of insulin outweigh potential cancer risks.