Insulin Glargine and Incidence of Cancer—An Ongoing Debate

Hemkens and colleagues1 published a registry study that demonstrated a significantly increased risk of a cancer diagnosis associated with high dosages of insulin glargine [relative risk (RR), 1.18; 95 % confidence interval (CI), 1.08–1.28, adjusted for various factors and insulin dosage]. However, the subsequent scientific discussion clearly revealed many methodological weaknesses of this study.2,3 Nevertheless, this study raised concerns among health care professionals about exposing diabetes patients to an unnecessary cancer risk by use of insulin glargine. Therefore, follow-up on this matter, based on currently available data and a closer look at the original publication, may help to clarify further the putative cancer risk of insulin glargine. The registry study1 demonstrated a significantly higher incidence of cancer (5.26 versus 1.86 cases per 100 patient years) in patients who were receiving a rather high dosage of insulin glargine (>40 U daily) compared with low dosages (<20 U daily). But a dose-dependent increase in cancer incidence was also observed in patients who were receiving human insulin (3.1 versus 1.73 cases per 100 patient years). Interestingly, only 13.5 % of patients on insulin glargine received a high dosage of>40 U daily, whereas 46 % of patients on human insulin received this dosage.1 In the previous discussion, this different distribution of the insulin dosages did not receive enough attention. Using the distribution data to standardize the cancer incidence, a standardized cancer incidence rate of 2.46 cases versus 2.68 cases per 100 patient years was the outcome among patients using insulin glargine versus human insulin (see Table 1). Thus i