FDA update: ongoing safety review of insulin glargine and cancer risk

FDA released a safety communication to update prescribers and patients about the ongoing review of insulin glargine (Lantus) that was initiated in July 2009.

FDA released a safety communication to update prescribers and patients about the ongoing review of insulin glargine (Lantus) that was initiated in July 2009. At that time, 3 observational studies were identified suggesting a link between insulin glargine use and increased cancer risk. Increased hazard of cancer ranged from 9% to 31% depending on dosing. A fourth observational study; however, suggested no such increased risk existed with insulin glargine.

Insulin glargine, a modified version of human insulin that allows for the control of blood sugar for extended periods of time, is used to control blood sugar in patients with both type 1 and type 2 diabetes. In 2009, insulin glargine was ranked 18th on the Top 200 Drugs list based upon sales of over $1.5 billion. It was the top-selling branded insulin.

According to Agency officials, “FDA has reviewed the 4 studies and has determined that the evidence presented in the studies is inconclusive, due to limitations in how the studies were designed and carried out and in the data available for analysis.”  They stressed, “These limitations prevent our ability to attribute the observed cancer risk to Lantus.”

In particular, a number of limitations in these 4 observational studies existed, including insufficient duration of follow up, limited data on insulin usage, failure to take into account prior or current use of other antidiabetic medications, and the likely presence of residual confounding.

FDA also reviewed data from the “Evaluation of Diabetic Retinopathy Progression in Subjects with Type 2 Diabetes Mellitus Treated with Oral Agents Plus Insulin” trial. This trial was a 5-year, randomized trial comparing insulin glargine to NPH insulin in individuals with type 2 diabetes. Its results do not support the hypothesis that insulin glargine increases the risk of cancer compared to NPH insulin (incidence of cancer: 5.8% vs 9.3% in the glargine and NPH insulin arms, respectively; OR=0.60; 95% CI, 0.36–0.99).

According to Craig I. Coleman, PharmD, from the University of Connecticut School of Pharmacy, “While such a finding from a randomized controlled trial is reassuring, this was a post-hoc analysis and as a result cancers had to be identified after the trial had concluded and were not adjudicated.”  He continued, “Future glargine trials should plan to pay closer attention to cancer as an end point.”

The Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial will do just that. FDA noted in their communication that ORIGIN has been amended to adjudicate all cases of cancer occurring during the trial. FDA’s communication noted, “An interim review of the data by an independent data monitoring committee did not show evidence of a signal for increased cancer risk.”

In addition to ORIGIN, Sanofi-aventis plans to conduct 3 more epidemiological studies and FDA plans on using the Veteran’s Administration patient database to further evaluate cancer risk associated with insulin glargine. 

Much of this new data is expected to be released later this year.