Sanofi-Aventis has responded to swiftly to claims from an analysis of its diabetes drug Lantus which link the drug with an increased risk of cancer.

The European Association for the Study of Diabetes published details from four studies of Lantus (insulin glargine) in its journal Diabetologia. Concerns about a possible link between use of the insulin analogue and increased cancer risk were raised by a German study of around 127,000 insulin-treated patients in an insurance database.

Compared with people using similar doses of human insulin, out of every 100 people who used Lantus over an average of about one-and-a-half years, one additional person was diagnosed with cancer. Of particular note in this study, says the EASD, was the finding that the increased risk of cancer was dose-dependent – for patients given a dose of 10U, Lantus raised the risk of cancer by 9% compared with human insulin, but for a dose of 50U, the increased risk was 31%.

Studies were then carried out using databases from Sweden, Scotland, and the UK. In the Swedish analysis, involving nearly 115,000 patients, those on Lantus alone were almost twice as likely to be diagnosed with breast cancer. The 49,000-patient Scottish study also found patients on Lantus were more likely to have cancer, including breast cancer, although the difference did not reach statistical significance, while the 10,000-patient UK study found no link.

Edwin Gale, editor of Diabetologia and Ulf Smith, president of EASD, emphasised limitations to the studies, the main one being that the groups of patients taking lantus insulin alone (generally older, higher blood pressure, more overweight) were different to those on other forms of insulin. Also, the numbers of cases of breast cancer in the Swedish and Scottish studies were very small, meaning the findings could have occurred due to chance.

They added that "we believe people are entitled to know that use of Lantus might be associated with greater risk, but this must also be balanced against the possibility that we might be causing unnecessary alarm by raising these concerns." Still, the EASD has passed on its findings to the European Medicines Agency and is in contact with Sanofi.

“While a prospective clinical trial would be the most scientifically sound manner to proceed”, Profs Gale and Smith say such a trial “would be slow, unfeasible and unethical”. They added that a “large combined analysis of the best available databases worldwide is the best way forward, and the EASD and Sanofi “are pledged to carry this investigation forward until we have either confirmed these preliminary observations or, more hopefully, finally put them to rest”.

EASD advises that patients do not stop taking Lantus but says that patients can consider alternatives. Profs Gale and Smith noted that people with diabetes have the option of using long-acting human insulin or a mixture of long- and short-acting human insulin twice a day instead of the once-daily Lantus.

'No definitive conclusions can be drawn'
Sanofi said it has just been made aware of the EASD data but noted that the results “clearly show that no definitive conclusions can be drawn regarding a possible causal relationship between Lantus use and the occurrence of malignancies, as the authors of the study point out”. The French drugmaker added that “clinical studies, which represent the gold standard of evidence”, do not indicate any association.

Jean-Pierre Lehner, the company’s chief medical officer, said that given the extensive clinical evidence covering over 70,000 patients and the results of post-marketing surveillance arising from 24 million patient-years of experience, Sanofi stands behind the safety of Lantus”. He added that “we consider that the results of these patient registries are not conclusive”.

Nevertheless, the news saw Sanofi shares slide 8.1% to 40.85 euros and could effect sales of Lantus which enjoyed a revenue rise of 27.1% to 747 million euros in the first quarter.