In Reply: Dr. Fountas et al highlight further data on insulin therapy and cancer risk, specifically in regard to insulin detemir and insulin degludec. Detemir first gained US Food and Drug Administration (FDA) approval in 2005 as a basal insulin, dosed once or twice daily. 1 Compared with regular human insulin, detemir has demonstrated proliferative and antiapoptotic activities in vitro in various cancer cell lines—eg, HCT-116 (colorectal cancer), PC-3 (prostate cancer), and MCF-7 (breast adenocarcinoma). 2 But clinically, detemir has not demonstrated increased cancer risk compared with other basal insulins in randomized controlled trials or cohort studies. 3–5
Degludec (U-200 insulin) is equal to twice the concentration of the usual U-100 insulin therapies presently available. In February 2013, the drug application for insulin degludec failed to obtain FDA approval, and the FDA requested additional data on cardiovascular safety. Thus, degludec is not currently available in the United States. 6
Besides ameliorating nocturnal hypoglycemia, 7 U-200 insulin may mitigate potential mitogenic effects. 8 However, there are still very few data on degludec compared with the amount of data on insulin glargine. Insulin analogues with a decreased dissociation rate from the insulin receptor are associated with higher mitogenic potency than metabolic potency compared with human insulin. 9,10 Degludec, like detemir, has an elevated dissociation rate from the insulin receptor, a low affinity for IGF-1 receptors, and a low mitogenic activity in vitro. 8
At this juncture, neither detemir nor degludec has been associated with higher cancer risk, but these therapies are relatively new. And as Dr. Fountas et al indicated, their safety, particularly in regard to cancer risk in diabetes patients, should continue to be assessed.