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

Abstract and Introduction

Abstract

People with diabetes, particularly those with type 2 diabetes, may be at an increased risk of cancer. Furthermore, their cancer risk may be modified by treatment choices. In this respect, metformin may be protective, whereas insulin and insulin analogues can function as growth factors and therefore have theoretical potential to promote tumour proliferation. Analogues causing inappropriate prolonged stimulation of the insulin receptor, or excess stimulation of the IGF-1 receptor, are the most likely to show mitogenic properties in laboratory studies. Some recent epidemiological studies appear to be consistent with these experimental findings, suggesting that there could be different relative risks for cancer associated with different insulins, although these studies have attracted some methodological criticism. However, it is biologically plausible that hormonal factors that influence neoplasia could begin to manifest their effects in surprisingly short timescales (within 2 years) and hence these epidemiological studies justify further research. Even if future research were to document an increase in cancer risk among insulin users, this would be unlikely to significantly diminish the favourable benefit-risk ratio for patients requiring insulin therapy. There is a need for further population studies and for the development of new laboratory models that are more sophisticated than previous experimental methods employed to assess potential tumour growth-promoting properties of insulins.

Introduction

Are diabetes and diabetes treatments associated with an increased risk of cancer? These questions have been exercising the minds of the clinical community since the recent publication of a series of epidemiologic studies (and accompanying editorial) that have investigated the relative risk for cancer incidence associated with the use of the basal insulin analogue, insulin glargine, or any insulin.[1–6] These publications have resurrected awareness and focused attention on an issue that first emerged more than a decade ago, when it was shown that artificial modification of the molecular structure of insulin could result in a peptide with increased mitogenic properties in cell lines and animal models.[7,8] Indeed, even earlier reports, for example Heuson et al. 1967,[9] provided evidence for links between insulin and neoplasia. This issue has been periodically studied in the intervening years and represented the a priori reason for conducting these observational studies.

The methodologies of each of the recent epidemiological studies have been subject to discussion, however, and published critiques and expert statements have assuaged initial concerns and successfully averted an over-reaction.[10] This is important because it is clear that insulin treatment has a favourable risk-benefit ratio. However, the existence of methodological flaws in these studies does not mean there are no risk differences between different insulins; no evidence of risk is not the same as evidence of no risk and it is possible that recent communiqués on the issue have been overly reassuring. As there are different insulin products available and given the possibility that these might differentially affect the growth rates of specific cancers in specific patients (and the possibility that risk differences might increase with longer follow-up), it is important to increase our understanding of all relevant issues so that informed choices can be made.

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