Diabetes, Glargine, and Cancer
The American Diabetes Association held its annual scientific meeting in Philadelphia June 8-12. During these five days, anyone who has any relationship to diabetes attends the meeting. Thousands of people attend from all over the world. The meetings are divided into different tracks so that scientists, physicians, psychologists, dieticians, nurses, and individuals with diabetes may find out the latest information in their own special interest group. The biggest problem is that too much is going on at the same time and one always comes away feeling that they may have “missed” something. In addition to symposiums that cover specific hot topics that showcase findings from evidence-based literature, posters, and abstracts also are presented that shed light on the various nuances of diabetes. Bench scientific research is presented along with clinical studies.
In 2009, there was much ado about the possible correlation between glargine and cancer in people with type 2 diabetes. Several studies published in Diabetologia indicated a relationship between different types of cancer and glargine. As such, investigators developed prospective studies to prove whether or not there was a causal relationship between glargine and cancer. At this year’s meeting, the results of the following paper were discussed providing much needed reassurance about the lack of causality between the basal insulin glargine and neoplasia. In the June 11, 2012 paper, “Basal Insulin and Cardiovascular and Other Outcomes in Dysglycemia” published online in the New England Journal of Medicine by The ORIGIN Trial investigators (10.1056/NEJMoa1203858), the authors state that therapy with basal insulin glargine for more than 6 years had a neutral effect on cardiovascular outcomes and cancers.
The authors randomly assigned 12,537 people (average age 63.5 years) with cardiovascular risk factors PLUS impaired fasting glucose, impaired glucose tolerance, or Type 2 DM to receive glargine or standard care (and to receive n-3 fatty acids or placebo).
What were the results?
- Median follow-up was 6.2 years
- Rates of cardiovascular outcomes were similar in the insulin glargine and standard care groups
- No increase in incident cancers
According to the authors, the data presented in this paper do NOT support the epidemiologic analyses that linked insulin in general or insulin glargine in particular to incident cancers during several years of exposure.
Why are these results significant?
Although the epidemiologic data linked insulin glargine to people with type 2 diabetes, there was a great concern in regard to the use of insulin glargine in those with type 1 diabetes that include young children, adolescents, and adults. Many people with type 1 diabetes have been on insulin, particularly glargine, for many years. Keep in mind that glargine has been used in every age group, often “off-label” (it is approved for children over 6 years of age), and that toddlers are often placed on glargine as the “basal” insulin in basal bolus therapy. After the publicity in regard to the Diabetologia papers, many parents of young children became quite concerned. It is very reassuring that this particular study had demonstrated no carcinogenic effects. All studies have limitations. However, the prospective design and the large number of randomized subjects strengthen this study. A major limitation, however, is that the study was funded by Sanofi-Aventis, the pharmaceutical company that manufactures glargine.
I should note, however, that Laurel Habel and colleagues of Kaiser Permanente, Oakland, presented an abstract at the ADA noting a “modest increase of breast cancer risk over 3 years among new glargine users compared with new users of insulin type 2 diabetes” (Sturmer T, et al "Risk for cancer after initiation of insulin glargine versus NPH -- A new user comparator drug cohort study" ADA2012. Habel L, et al "Insulin glargine and cancer risk: Kaiser Permanente California Cohort Study" ADA 2012.) However, the authors demonstrated “no increased risk of breast cancer in their huge database who were on insulin for a longer period of time and switched to glargine after treatment with NPH and think that this might have been a chance finding. A limitation of this 3-year study is that the patients on glargine need to be followed for a longer period of time and future prospective studies will need to be conducted.
Keep in mind that Detemir, the other basal, relatively peakless insulin, has not been utilized in the studies. I suspect that it also would be found to have no relationship to an increased incidence of cancer. Clearly, additional prospective studies will be performed that will hopefully further support the above data and provide reassuring evidence that an extremely therapeutic basal insulin does not lead to an increased incidence of cancer.
Knickers update: Knickers is now 7 ½ months old and has completed 5 out of 7 obedience sessions at the Greenbelt Dog Training School. (I, too, have been successfully trained by Knickers to indulge his whims!) We are hopeful that he will shortly complete and fulfill all Children’s National Medical Center requirements and soon accompany me, as my “pet therapist,” to all the outpatient clinics around the Washington Capital area beltway.