Insulin Glargine (LANTUS) and Cancer: Is There a Link?

You may have read the recent newspaper reports about evidence from European studies showing a possible link between the diabetes drug insulin glargine (LANTUS) and cancer.

However, Public Citizen drug safety experts have reviewed this evidence and have found that diabetes patients do not need to be alarmed about this possible link and should not stop using the drug.

Insulin glargine, an artificial form of insulin used to treat diabetes, is injected only once a day. While taking insulin glargine, other, shorter-acting forms of insulin may also be required to yield optimal blood sugar control.

Manufactured by Sanofi-Aventis, insulin glargine was ranked 21st in retail drug sales in 2008 with $1.48 billion in sales.

Study unconvincing

An article published June 26 in the journal Diabetologia, which described a German study of 127,000 diabetes patients taking various forms of insulin, sparked the news coverage.

The study detected an increased risk of total cancers that was dependent upon the dose of glargine insulin used. That is to say, when researchers looked at the occurrence of many different kinds of cancers combined, they saw statistically significantly higher rates of cancer in patients using glargine insulin. However, there was no consistent statistically significant increase in any particular cancer in patients taking insulin glargine.

While cancer of all kinds was relatively rare during these studies, compared to patients taking human insulin, there was an increased risk of 9 percent for those taking 10 units of glargine insulin, a 19 percent increased risk for those taking 30 units and a 31 percent increased risk for those taking 50 units. In some analyses increased risks as high as 59 percent were observed.

There was no consistent increase in either total cancers or particular cancers with the use of other artificial insulins such as insulin aspart (NOVOLOG/NOVORAPID) and insulin lispro (HUMALOG).

These findings mirror findings from test tube studies identifying glargine insulin as potentially stimulating cell division and the growth of cancer cells.

But the study suffered from several limitations. Most fundamentally, it was not a randomized, controlled trial, so patients taking glargine insulin may have been different than other patients in the study. (In particular, they may have been at more at risk for cancer.)

In addition, the study followed patients for under two years, considerably less than is typically required for known cancer-causing agents to produce cancer.

Still, the findings were concerning enough that the editors of Diabetologia arranged for three additional studies to be published in the same issue, though all suffer from the same defect of not being randomized. A Swedish study found that patients using insulin glargine had an almost doubled risk of getting breast cancer, but total cancers were not increased. A Scottish study found a non-statistically significant risk of breast cancer in patients using glargine and a mixed picture for the risk of total cancers. A study from the entire United Kingdom did not find any link between insulin glargine and cancer.

Together, these studies present a confusing picture. Three of the four studies presented a potential link between glargine and cancer, but none of the studies were long enough to be fully convincing. Moreover, the data presented in the studies was inconsistent; two studies showed a potential link with breast cancer, while others pointed to total cancer, but not any specific cancer. Such inconsistencies make it difficult to conclude that there exists a definite link between glargine insulin and cancer.

Moreover, Sanofi-Aventis has made public very limited information on an actual randomized, controlled trial it is sponsoring. Although the study is not expected to be complete until 2011, an interim analysis has found that "there is no cause for concern."

Expert opinions

Many diabetes organizations around the world, including the American Diabetes Association, Australian Diabetes Society and European Medicines Agency, have reacted to the new data. Most focus on the inconsistencies in the study results and the need for more research.

The U.S. Food and Drug Administration issued an "early communication" July 1 describing the studies, identifying their deficiencies and explaining the kinds of research it would be evaluating as part of a broader assessment of the drug’s cancer-causing potential. The agency also recommended that patients not stop taking glargine insulin without consulting their physicians.

This approach seems prudent to us. The data are simply not clear enough to permit a clear conclusion that glargine insulin causes cancer, let alone that its risks would then exceed its benefits. We look forward to the publication of more research on the topic and urge you to not stop taking the drug without consulting with your doctor, lest the control of your diabetes worsen without it.