Insulin Lantus and Cancer: Where Do We Stand? (Medical Horizons)

Aly A. Misha'l

Abstract


The controversy of whether the Insulin Lantus (glargine) causes cancer has been raised for more than 2 years.

In view of the fact that millions around the world and thousands in Jordan are using this type of insulin, it became mandatory to focus on the issue of its possible carcinogenecity.

What is Lantus (glargine)?

It is the first of the long-acting insulin analogues made by the recombinant DNA technique, introduced in 2001.

It has the property of slower solubility at the subcutaneous injection site, forming a depot from which insulin is slowly released. This feature provides an advantage of stable 24 hours blood glucose concentrations by a once daily injection, with no blood glucose peak as seen with the shorter acting insulins.

Insulins bind to insulin receptors to exert their glucose lowering effects, but also they bind to the Insulin Growth Factor Receptor (IGF-R), which induces cell proliferation. Significantly, glargine has a much higher affinity for both receptors than human insulin. This can lead to a sustained activation of the IGF-receptor, resulting in enhanced cell growth.

Indeed, preclinical research has shown that only glargine showed a significantly higher proliferative effect on breast cancer cells compared to other insulins.

Furthermore, insulin analogues display IGF-I-like
mitogenic and anti-apoptotic activities in cultured cancer cells. This means that they stimulate cell proliferation, and prevent programmed death of cancer cells.

Some animal experiments have been conducted. Glargine was found to induce histiocytomas in male rats, but no other tumorigenic properties, as stated in the (product information). These studies, however, did not examine tumor promoting properties.

These characteristics have alarmed researchers about the possibility of increased cancer risk of glargine.

Concerns about possible increased cancer risk of glargine boosted researchers to conduct several studies, published in the literature, especially in Diabetologia, the Journal of European Assoicaiton for the Study of Diabetes (EASD).

All the studies were retrospective, except for one small study, which was a post-hoc analysis of a randomized study, conducted by Sanofi-Aventis, the manufacturing company itself. This small study (only 1000 patients) was not convincing enough to exclude cancer risk.

The first study was conducted by Hemkens et al in Germany. 127,031 patients were included, who were on various types of insulin. 23,855 of them were on glargine. Mean follow-up time was 1.63 years. After statistical modeling, a dose dependent increase in cancer risk was found for treatment with glargine compared with human insulin (P<0.0001), with an adjusted HR of 1.31 (95% CI 1.20-1.42) for a daily dose of 50IU.

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