In a large observational study, women with type 2 diabetes who received long-acting insulin glargine (Lantus, Sanofi) had a 1.4-fold increased risk of breast cancer compared with women who were given intermediate-acting neutral protamine Hagedorn (NPH) insulin during roughly 4 years and up to 12 years of follow-up.
In contrast, those who received insulin detemir (Levemir, Novo Nordisk) did not have any increased risk of breast cancer.
Of note, the breast-cancer signal with insulin glargine was only significant among prior insulin users and not new users.
And this signal does not mean clinicians should change clinical practice without a review by regulatory agencies, caution the investigators, led by Jennifer W Wu, MD, of McGill University, Montreal, Quebec, who published their paper in the Journal of Clinical Oncology.
“Despite these findings, the benefits and risk of insulin glargine must be considered by drug regulatory agencies before any changes in clinical practice can be made,” they conclude.
The fact that the increased risk of breast cancer was only seen in women with prior exposure to insulin, “an unusual group of type 2 [diabetes] women,” suggests “the safety signals may be nuanced, with specific types of insulin,” said Craig Currie, PhD, an epidemiologist from Cardiff University, Wales, who was not involved with the study.
Nevertheless the “findings add to an increasing body of evidence that questions the safety of insulin in people with type 2 diabetes more generally,” he told Medscape Medical News in an email.
New Study as Long-Acting Insulins Have Been Available for Longer
The issue of cancer risk associated with insulin, which is a potential growth factor, isn’t new and has reared its head before in relation to insulin glargine in particular.
Several observational studies have looked at whether insulin glargine is associated with an increased risk of breast cancer and have come up with conflicting results, Dr Wu and colleagues explain as background.
Moreover, in the randomized Outcomes Reduction Insulin Glargine Intervention (ORIGIN) trial, which had adjudicated cancer outcomes reported in 2013, only roughly 4000 of the 12,500 patients were women, and there were only 56 cases of breast cancer during follow-up, which was “insufficient power for site-specific cancers such as breast and also…too short a follow-up for the necessary latency.”
Thus “to date, the US Food and Drug Administration finds the evidence is inconclusive and suggests that more epidemiologic data are needed,” they observe.
So they aimed to assess the risk of breast cancer with insulin analogs, “now that these insulins have been on the market for a longer time.”
They identified 22,395 women with type 2 diabetes in the UK Clinical Practice Research Datalink (CPRD) who had not been prescribed insulin before age 40, had not had gestational diabetes or any cancer, but had received at least one prescription of insulin glargine, detemir, or NPH during 2002–2012.
On average, the women received 5.4 to 5.8 insulin prescriptions each year.
During follow-up, 108 of 9549 women who received NPH, 176 of 9575 women who received insulin glargine, and 37 of 3271 women who received insulin detemir developed breast cancer.
The incidence rates of breast cancer were 35.1, 48.7, and 14.8 per 1000 person-years for women who received NPH, glargine, and detemir, respectively.
New Insulin Users Not at Risk?
Those who received insulin glargine for 5 or more years had a roughly twofold increased risk of breast cancer compared with the reference group (women who received NPH) and women who were switched to insulin glargine from another insulin had an approximately 1.5-fold increased risk of developing breast cancer.