Insulin Analogues and Cancer Risk: Cause for Concern or Cause Célèbre?

M. Pollak; D. Russell-Jones

Disclosures

Int J Clin Pract. 2010;65(5):628-636. 

In This Article

What Next?

More questions have been raised than have been answered by the data now available to us and we hardly need state that further research is needed. Further independent observational and epidemiological studies are indicated, but expectations should be tempered; these may not be able to provide a reliable quantification of relative risks unless the effect size is large and will always be subject to confounding issues. On the other hand, the effect of insulin analogues on cancer risk or development is unlikely to form a suitable subject for a prospective interventional controlled trial. We therefore need imaginative alternatives. These might include careful studies of tumour biology and cell signalling pathways in neoplastic tissue from cancer patients who also have diabetes and are receiving insulin, and the development of improved animal models.

In the past, carcinogenicity of insulins was assessed experimentally in large part by using 2-year exposures in non-diabetic rodents; this method led to some deaths because of hypoglycaemia and is sub-optimum for assaying the effects of treatment on pre-existing cancers. Therefore, it will be of interest to compare tumour growth in control hosts, untreated diabetic hosts and diabetic hosts receiving various insulins, as an example. There is also a need to develop a validated functional assay of the mitogenicity of human serum and to determine if this is influenced by type 1 or type 2 diabetes or by various diabetes treatments.

It must be emphasised that type 2 diabetes has been associated with increased cancer risk, as discussed above. This may be related to elevated endogenous insulin levels seen in the setting of insulin resistance of classic insulin target organs, while tumors remain insulin sensitive, but other mechanisms have not been ruled out. Similarities and differences in the effects of endogenous insulin and various administered insulins on cancer endpoints in experimental models requires study.

In the meantime, in agreement with statements issued by the major diabetes associations, there is no need to panic; insulin has an excellent risk-benefit ratio and any absolute risk differences between analogues are likely to be small. However, careful consideration of the choices available might be considered wise for patients who are at high biological risk of cancer (for example, those with family or personal history of cancer) and many of these patients will appreciate discussion of these issues if they require pharmacotherapy for diabetes. The point at which insulin initiation takes place might also be usefully reconsidered, although there are currently few risk-benefit data to guide decisions on this issue. An increased risk of cancer associated with insulin therapy in general or with certain modified insulins cannot be excluded on the basis of available data, but this must be considered in the context of the relatively high and well-documented risks of morbid endpoints encountered when diabetes is poorly controlled.

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